MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Genetics' source. Tue, 16 Mar 2010 17:23:28 +0100 http://www.medworm.com/index.php?rid=3211063&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F2%2F607-a%3Frss%3D1 (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=3211063 Tue, 26 Jan 2010 22:34:09 +0100 3211063 http://www.medworm.com/index.php?rid=3211062&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F2%2F607%3Frss%3D1 (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=3211062 Tue, 26 Jan 2010 22:34:09 +0100 3211062 http://www.medworm.com/index.php?rid=3211061&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F2%2F595%3Frss%3D1 We have leveraged the reference sequence of a boxer to construct the first complete linkage map for the domestic dog. The new map improves access to the dog's unique biology, from human disease counterparts to fascinating evolutionary adaptations. The map was constructed with ~3000 microsatellite markers developed from the reference sequence. Familial resources afforded 450 mostly phase-known meioses for map assembly. The genotype data supported a framework map with ~1500 loci. An additional ~1500 markers served as map validators, contributing modestly to estimates of recombination rate but supporting the framework content. Data from ~22,000 SNPs informing on a subset of meioses supported map integrity. The sex-averaged map extended 21 M and revealed marked region- and sex-specific differe... Genetics journals http://www.medworm.com/rss/comments.php?id=3211061 Tue, 26 Jan 2010 22:34:09 +0100 3211061 http://www.medworm.com/index.php?rid=3211060&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F2%2F587%3Frss%3D1 Understanding complex genotype-by-environment interactions (GEIs) is crucial for understanding phenotypic variation. An important factor often overlooked in GEI studies is time. We measured the contribution of GEIs to expression variation in four nonlaboratory Saccharomyces cerevisiae strains responding dynamically to a 25°–37° heat shock. GEI was a major force explaining expression variation, affecting 55% of the genes analyzed. Importantly, almost half of these expression patterns showed GEI influence only during the transition between environments, but not in acclimated cells. This class reveals a genotype-by-environment-by-time interaction that affected expression of a large fraction of yeast genes. Strikingly, although transcripts subject to persistent GEI effects were e... Genetics journals http://www.medworm.com/rss/comments.php?id=3211060 Tue, 26 Jan 2010 22:34:09 +0100 3211060 http://www.medworm.com/index.php?rid=3211059&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F2%2F571%3Frss%3D1 A major problem in population genetics is understanding how the genomic pattern of polymorphism is shaped by natural selection and the demographic history of populations. Complex population dynamics confounds patterns of variation and poses serious challenges for identifying genomic imprints of selection. We examine patterns of polymorphism using computer simulations and provide analytical predictions for hitchhiking effects under two models of adaptive niche expansion. The population split (PS) model assumes the separation of a founding population followed by directional selection in the new environment. Here, the new population undergoes a bottleneck and later expands in size. This model has been used in previous studies to account for demographic effects when testing for signatures of s... Genetics journals http://www.medworm.com/rss/comments.php?id=3211059 Tue, 26 Jan 2010 22:34:09 +0100 3211059 http://www.medworm.com/index.php?rid=3211058&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F2%2F557%3Frss%3D1 Conditionally expressed genes have the property that every individual in a population carries and transmits the gene, but only a fraction, , expresses the gene and exposes it to natural selection. We show that a consequence of this pattern of inheritance and expression is a weakening of the strength of natural selection, allowing deleterious mutations to accumulate within and between species and inhibiting the spread of beneficial mutations. We extend previous theory to show that conditional expression in space and time have approximately equivalent effects on relaxing the strength of selection and that the effect holds in a spatially heterogeneous environment even with low migration rates among patches. We support our analytical approximations with computer simulations and delineate the p... Genetics journals http://www.medworm.com/rss/comments.php?id=3211058 Tue, 26 Jan 2010 22:34:09 +0100 3211058 http://www.medworm.com/index.php?rid=3211057&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F2%2F547%3Frss%3D1 In this study we performed the converse experiment: we replaced seven suboptimal leucine codons that occur naturally in the Drosophila melanogaster Adh gene with the optimal codon. We then compared the in vivo ADH activities imparted by the wild-type and mutant alleles. The introduction of optimal leucine codons led to an increase in ADH activity in third-instar larvae. In adult flies, however, the introduction of optimal codons led to a decrease in ADH activity. There is no evidence that other selectively constrained features of the Adh gene, or its rate of transcription, were altered by the synonymous replacements. These results are consistent with translational selection for codon bias being stronger in the larval stage and suggest that there may be a selective conflict over optimal cod... Genetics journals http://www.medworm.com/rss/comments.php?id=3211057 Tue, 26 Jan 2010 22:34:09 +0100 3211057 http://www.medworm.com/index.php?rid=3211056&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F2%2F529%3Frss%3D1 Neutral nucleotide diversity does not scale with population size as expected, and this "paradox of variation" is especially severe for animal mitochondria. Adaptive selective sweeps are often proposed as a major cause, but a plausible alternative is selection against large numbers of weakly deleterious mutations subject to Hill–Robertson interference. The mitochondrial genealogies of several species of whale lice (Amphipoda: Cyamus) are consistently too short relative to neutral-theory expectations, and they are also distorted in shape (branch-length proportions) and topology (relative sister-clade sizes). This pattern is not easily explained by adaptive sweeps or demographic history, but it can be reproduced in models of interference among forward and back mutations at large numbers... Genetics journals http://www.medworm.com/rss/comments.php?id=3211056 Tue, 26 Jan 2010 22:34:09 +0100 3211056 http://www.medworm.com/index.php?rid=3211055&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F2%2F517%3Frss%3D1 Interlocus gene conversion can homogenize DNA sequences of duplicated regions with high homology. Such nonvertical events sometimes cause a misleading evolutionary interpretation of data when the effect of gene conversion is ignored. To avoid this problem, it is crucial to test the data for the presence of gene conversion. Here, we performed extensive simulations to compare four major methods to detect gene conversion. One might expect that the power increases with increase of the gene conversion rate. However, we found this is true for only two methods. For the other two, limited power is expected when gene conversion is too frequent. We suggest using multiple methods to minimize the chance of missing the footprint of gene conversion. (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=3211055 Tue, 26 Jan 2010 22:34:09 +0100 3211055 http://www.medworm.com/index.php?rid=3211054&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F2%2F503%3Frss%3D1 Though much has been learned about the process of ovarian follicle maturation through studies of oogenesis in both vertebrate and invertebrate systems, less is known about how follicles form initially. In Drosophila, two somatic follicle stem cells (FSCs) in each ovariole give rise to all polar cells, stalk cells, and main body cells needed to form each follicle. We show that one daughter from each FSC founds most follicles but that cell type specification is independent of cell lineage, in contrast to previous claims of an early polar/stalk lineage restriction. Instead, key intercellular signals begin early and guide cell behavior. An initial Notch signal from germ cells is required for FSC daughters to migrate across the ovariole and on occasion to replace the opposite stem cell. Both an... Genetics journals http://www.medworm.com/rss/comments.php?id=3211054 Tue, 26 Jan 2010 22:34:09 +0100 3211054 http://www.medworm.com/index.php?rid=3211053&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F2%2F483%3Frss%3D1 In an attempt to understand whether it should be expected that some genes tend to be used disproportionately often by natural selection, we investigated two related phenomena: the evolution of flux control among enzymes in a metabolic pathway and properties of adaptive substitutions in pathway enzymes. These two phenomena are related by the principle that adaptive substitutions should occur more frequently in enzymes with greater flux control. Predicting which enzymes will be preferentially involved in adaptive evolution thus requires an evolutionary theory of flux control. We investigated the evolution of enzyme control in metabolic pathways with two models of enzyme kinetics: metabolic control theory (MCT) and Michaelis–Menten saturation kinetics (SK). Our models generate two main ... Genetics journals http://www.medworm.com/rss/comments.php?id=3211053 Tue, 26 Jan 2010 22:34:09 +0100 3211053 http://www.medworm.com/index.php?rid=3211052&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F2%2F467%3Frss%3D1 Adaptation often involves the acquisition of a large number of genomic changes that arise as mutations in single individuals. In asexual populations, combinations of mutations can fix only when they arise in the same lineage, but for populations in which genetic information is exchanged, beneficial mutations can arise in different individuals and be combined later. In large populations, when the product of the population size N and the total beneficial mutation rate Ub is large, many new beneficial alleles can be segregating in the population simultaneously. We calculate the rate of adaptation, v, in several models of such sexual populations and show that v is linear in NUb only in sufficiently small populations. In large populations, v increases much more slowly as log NUb. The prefactor ... Genetics journals http://www.medworm.com/rss/comments.php?id=3211052 Tue, 26 Jan 2010 22:34:09 +0100 3211052 http://www.medworm.com/index.php?rid=3211051&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F2%2F455%3Frss%3D1 Characterizing the genetic and molecular basis of hybrid incompatibilities is a first step toward understanding their evolutionary origins. We fine mapped the nuclear restorer (Rf) of cytoplasm-dependent anther sterility in Mimulus hybrids by identifying and targeting regions of the Mimulus guttatus genome containing large numbers of candidate pentatricopeptide repeat genes (PPRs). The single Mendelian locus Rf was first isolated to a 1.3-cM region on linkage group 7 that spans the genome's largest cluster of PPRs, then split into two tightly linked loci (Rf1 and Rf2) by <10 recombination events in a large (N = 6153) fine-mapping population. Progeny testing of fertile recombinants demonstrated that a dominant M. guttatus allele at each Rf locus was sufficient to restore fertility. Each ... Genetics journals http://www.medworm.com/rss/comments.php?id=3211051 Tue, 26 Jan 2010 22:34:09 +0100 3211051 http://www.medworm.com/index.php?rid=3211050&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F2%2F439%3Frss%3D1 In angiosperms, spermatozoa go by pair in each pollen grain and fertilize, in addition to the egg cell, one of its sister cells, called the central cell. This "double fertilization" leads to the embryo on the one hand and to its nutritive tissue, the endosperm, on the other hand. In addition, in most flowering plants, the endosperm is triploid because of a doubled maternal genetic contribution in the central cell. Most of the hypotheses trying to explain these eccentricities rest on the assumption of a male/female conflict over seed resource allocation. We investigate an alternative hypothesis on the basis of the masking of deleterious alleles. Using analytical methods, we show that a doubled maternal contribution and double fertilization tend to be favored in a wide range of conditions wh... Genetics journals http://www.medworm.com/rss/comments.php?id=3211050 Tue, 26 Jan 2010 22:34:09 +0100 3211050 http://www.medworm.com/index.php?rid=3211049&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F2%2F429%3Frss%3D1 The coalescent with recombination is a very useful tool in molecular population genetics. Under this framework, genealogies often represent the evolution of the substitution unit, and because of this, the few coalescent algorithms implemented for the simulation of coding sequences force recombination to occur only between codons. However, it is clear that recombination is expected to occur most often within codons. Here we have developed an algorithm that can evolve coding sequences under an ancestral recombination graph that represents the genealogies at each nucleotide site, thereby allowing for intracodon recombination. The algorithm is a modification of Hudson's coalescent in which, in addition to keeping track of events occurring in the ancestral material that reaches the sample, we n... Genetics journals http://www.medworm.com/rss/comments.php?id=3211049 Tue, 26 Jan 2010 22:34:09 +0100 3211049 http://www.medworm.com/index.php?rid=3211048&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F2%2F411%3Frss%3D1 Tetraploid sour cherry (Prunus cerasus) has an S-RNase-based gametophytic self-incompatibility (GSI) system; however, individuals can be either self-incompatible (SI) or self-compatible (SC). Unlike the situation in the Solanaceae, where self-compatibility accompanying polyploidization is often due to the compatibility of heteroallelic pollen, the genotype-dependent loss of SI in sour cherry is due to the compatibility of pollen containing two nonfunctional S haplotypes. Sour cherry individuals with the S4S6S36aS36b genotype are predicted to be SC, as only pollen containing both nonfunctional S36a and S36b haplotypes would be SC. However, we previously found that individuals of this genotype were SI. Here we describe four nonfunctional S36 variants. Our molecular analyses identified a muta... Genetics journals http://www.medworm.com/rss/comments.php?id=3211048 Tue, 26 Jan 2010 22:34:09 +0100 3211048 http://www.medworm.com/index.php?rid=3211047&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F2%2F401%3Frss%3D1 Many studies have demonstrated the rapid diversification of reproductive genes that function after mating but before fertilization. This process might lead to the evolution of postmating, prezygotic barriers between species. Here, I investigate the phenotypic and genetic basis of postmating, prezygotic isolation between two closely related species of Drosophila, Drosophila virilis and D. americana. I show that a strong barrier to interspecific fertilization results in a 99% reduction in progeny production. A genetic interaction among maternal and paternal alleles at only a few loci prevents the fertilization of D. virilis females by D. americana males. These loci are autosomal and isolation acts recessively; the fertilization incompatibility is caused by at least two loci in the maternal D... Genetics journals http://www.medworm.com/rss/comments.php?id=3211047 Tue, 26 Jan 2010 22:34:08 +0100 3211047 http://www.medworm.com/index.php?rid=3211046&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F2%2F393%3Frss%3D1 Epigenetically inherited aggregates of the yeast prion [PSI+] cause genomewide readthrough translation that sometimes increases evolvability in certain harsh environments. The effects of natural selection on modifiers of [PSI+] appearance have been the subject of much debate. It seems likely that [PSI+] would be at least mildly deleterious in most environments, but this may be counteracted by its evolvability properties on rare occasions. Indirect selection on modifiers of [PSI+] is predicted to depend primarily on the spontaneous [PSI+] appearance rate, but this critical parameter has not previously been adequately measured. Here we measure this epimutation rate accurately and precisely as 5.8 x 10–7 per generation, using a fluctuation test. We also determine that genetic "mimics" o... Genetics journals http://www.medworm.com/rss/comments.php?id=3211046 Tue, 26 Jan 2010 22:34:08 +0100 3211046 http://www.medworm.com/index.php?rid=3211045&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F2%2F381%3Frss%3D1 Inbreeding in highly selfing populations reduces effective size and, combined with demographic conditions associated with selfing, this can erode genetic diversity and increase population differentiation. Here we investigate the role that variation in mating patterns and demographic history play in shaping the distribution of nucleotide variation within and among populations of the annual neotropical colonizing plant Eichhornia paniculata, a species with wide variation in selfing rates. We sequenced 10 EST-derived nuclear loci in 225 individuals from 25 populations sampled from much of the geographic range and used coalescent simulations to investigate demographic history. Highly selfing populations exhibited moderate reductions in diversity but there was no significant difference in varia... Genetics journals http://www.medworm.com/rss/comments.php?id=3211045 Tue, 26 Jan 2010 22:34:08 +0100 3211045 http://www.medworm.com/index.php?rid=3211044&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F2%2F363%3Frss%3D1 Most methods for studying divergence with gene flow rely upon data from many individuals at few loci. Such data can be useful for inferring recent population history but they are unlikely to contain sufficient information about older events. However, the growing availability of genome sequences suggests a different kind of sampling scheme, one that may be more suited to studying relatively ancient divergence. Data sets extracted from whole-genome alignments may represent very few individuals but contain a very large number of loci. To take advantage of such data we developed a new maximum-likelihood method for genomic data under the isolation-with-migration model. Unlike many coalescent-based likelihood methods, our method does not rely on Monte Carlo sampling of genealogies, but rather pr... Genetics journals http://www.medworm.com/rss/comments.php?id=3211044 Tue, 26 Jan 2010 22:34:08 +0100 3211044 http://www.medworm.com/index.php?rid=3211043&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F2%2F351%3Frss%3D1 The Neurospora circadian oscillator comprises FREQUENCY (FRQ) and its transcription activator, the White Collar Complex (WCC). Repression of WCC's transcriptional activity by FRQ via negative feedback is indispensable for clock function. An unbiased genetic screen that targeted mutants with defects in negative feedback regulation yielded a fully viable arrhythmic strain bearing a novel allele of FRQ-interacting RNA helicase (frh), an essential gene that encodes a putative exosome component protein. In the allele, frhR806H, clock function is completely disturbed, while roles of FRQ-interacting RNA helicase (FRH) essential for viability are left intact. FRHR806H still interacts with FRQ, but interaction between the FRQ–FRHR806H complex (FFC) and WCC is severely affected. Phosphorylatio... Genetics journals http://www.medworm.com/rss/comments.php?id=3211043 Tue, 26 Jan 2010 22:34:08 +0100 3211043 http://www.medworm.com/index.php?rid=3211042&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F2%2F343%3Frss%3D1 Rice (Oryza sativa L.) inflorescence (panicle) architecture is an important agronomic trait for rice breeding. A number of high-yielding japonica rice strains, characterized by an erect panicle (EP) of their architecture, have been released as commercial varieties in China. But no EP-type indica varieties are released so far. Here, we identified two allelic erect-panicle mutants in indica rice, erect panicle2-1 (ep2-1) and erect panicle2-2 (ep2-2), exhibiting the characteristic erect panicle phenotype. Both mutants were derived from spontaneous mutation. We cloned the EP2 gene by way of a map-based cloning strategy, and a transgenic complementation test rescued the phenotype of ep2-1. Anatomical investigations revealed that the ep2 mutants have more vascular bundles and a thicker stem than... Genetics journals http://www.medworm.com/rss/comments.php?id=3211042 Tue, 26 Jan 2010 22:34:08 +0100 3211042 http://www.medworm.com/index.php?rid=3211041&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F2%2F335%3Frss%3D1 The proteasome homeostasis in Saccharomyces cerevisiae is regulated by a negative feedback loop in which the transcription factor Rpn4 induces the proteasome genes and is rapidly degraded by the assembled proteasome. In addition to the proteasome genes, Rpn4 regulates numerous other genes involved in a wide range of cellular pathways. Therefore, the Rpn4–proteasome negative feedback circuit not only controls proteasome abundance, but also gauges the expression of other Rpn4 target genes. Our previous work has shown that Rpn4-induced gene expression is critical for cell viability under stressed conditions. Here we investigate whether proteasomal degradation of Rpn4 is also important for cell survival in response to stress. To this end, we generate a stabilized Rpn4 mutant (Rpn4*) that... Genetics journals http://www.medworm.com/rss/comments.php?id=3211041 Tue, 26 Jan 2010 22:34:08 +0100 3211041 http://www.medworm.com/index.php?rid=3211040&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F2%2F321%3Frss%3D1 Spt4–Spt5, a general transcription elongation factor for RNA polymerase II, also has roles in chromatin regulation. However, the relationships between these functions are not clear. Previously, we isolated suppressors of a Saccharomyces cerevisiae spt5 mutation in genes encoding members of the Paf1 complex, which regulates several cotranscriptional histone modifications, and Chd1, a chromatin remodeling enzyme. Here, we show that this suppression of spt5 can result from loss of histone H3 lysines 4 or 36 methylation, or reduced recruitment of Chd1 or the Rpd3S complex. These spt5 suppressors also rescue the synthetic growth defects observed in spt5 mutants that also lack elongation factor TFIIS. Using a FLO8 reporter gene, we found that a chd1 mutation caused cryptic initiation of tr... Genetics journals http://www.medworm.com/rss/comments.php?id=3211040 Tue, 26 Jan 2010 22:34:08 +0100 3211040 http://www.medworm.com/index.php?rid=3211039&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F2%2F317%3Frss%3D1 Much of our understanding of how organisms develop and function is derived from the extraordinarily powerful, classic approach of screening for mutant organisms in which a specific biological process is disrupted. Reaping the fruits of such forward genetic screens in metazoan model systems like Drosophila, Caenorhabditis elegans, or zebrafish traditionally involves time-consuming positional cloning strategies that result in the identification of the mutant locus. Whole genome sequencing (WGS) has begun to provide an effective alternative to this approach through direct pinpointing of the molecular lesion in a mutated strain isolated from a genetic screen. Apart from significantly altering the pace and costs of genetic analysis, WGS also provides new perspectives on solving genetic problems... Genetics journals http://www.medworm.com/rss/comments.php?id=3211039 Tue, 26 Jan 2010 22:34:08 +0100 3211039 http://www.medworm.com/index.php?rid=3211038&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F2%2FNP%3Frss%3D1 (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=3211038 Tue, 26 Jan 2010 22:34:08 +0100 3211038 http://www.medworm.com/index.php?rid=3155475&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F1%2F313%3Frss%3D1 Several recent studies have suggested that F1 hybrid male lethality in crosses between Drosophila melanogaster and D. simulans is due to a failure in dosage compensation, caused by incompatibilities between D. simulans dosage compensation proteins and the D. melanogaster X chromosome. Contrary to the predictions of this hypothesis, mutations in four essential D. melanogaster dosage compensation genes are shown here to moderately increase rather than decrease hybrid male viability. (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=3155475 Fri, 08 Jan 2010 22:15:35 +0100 3155475 http://www.medworm.com/index.php?rid=3155474&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F1%2F309%3Frss%3D1 Previously, we observed that heterochromatic 4 and Y chromosomes that had experienced breakage in the male germline were frequently transmitted to progeny. Their behavior suggested that they carried functional telomeres. Here we show that efficient healing by de novo telomere addition is not unique to heterochromatic breaks. (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=3155474 Fri, 08 Jan 2010 22:15:35 +0100 3155474 http://www.medworm.com/index.php?rid=3155473&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F1%2F295%3Frss%3D1 The Y chromosome of Drosophila melanogaster has <20 protein-coding genes. These genes originated from the duplication of autosomal genes and have male-related functions. In 1993, Russell and Kaiser found three Y-linked pseudogenes of the Mst77F gene, which is a testis-expressed autosomal gene that is essential for male fertility. We did a thorough search using experimental and computational methods and found 18 Y-linked copies of this gene (named Mst77Y-1–Mst77Y-18). Ten Mst77Y genes encode defective proteins and the other eight are potentially functional. These eight genes produce ~20% of the functional Mst77F-like mRNA, and molecular evolutionary analysis shows that they evolved under purifying selection. Hence several Mst77Y genes have all the features of functional genes. Mst7... Genetics journals http://www.medworm.com/rss/comments.php?id=3155473 Fri, 08 Jan 2010 22:15:35 +0100 3155473 http://www.medworm.com/index.php?rid=3155472&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F1%2F285%3Frss%3D1 Communities of interdependent microbes, found in diverse natural contexts, have recently attracted the attention of bioengineers. Such consortia have potential applications in biosynthesis, with metabolic tasks distributed over several phenotypes, and in live-cell microbicide therapies where phenotypic diversity might aid in immune evasion. Here we investigate one route to generate synthetic microbial consortia and to regulate their phenotypic diversity, through programmed genetic interconversions. In our theoretical model, genotypes involve ordered combinations of DNA elements representing promoters, protein-coding genes, and transcription terminators; genotypic interconversions are driven by a recombinase enzyme that inverts DNA segments; and selectable phenotypes correspond to distinct ... Genetics journals http://www.medworm.com/rss/comments.php?id=3155472 Fri, 08 Jan 2010 22:15:35 +0100 3155472 http://www.medworm.com/index.php?rid=3155471&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F1%2F277%3Frss%3D1 The objectives of the study were to investigate whether there is support for genetic variation for mortality and to study the quality of fit and predictive properties of the various models. In both breeds, the model that provided the best fit to the data was the standard binomial hierarchical model. The model that performed best in terms of the ability to predict the distribution of stillbirths was the hierarchical zero-inflated negative binomial model. The best fit of the binomial hierarchical model and of the zero-inflated hierarchical negative binomial model was obtained when genetic variation was included as a parameter. For the hierarchical binomial model, the estimate of the posterior mean of the additive genetic variance (posterior standard deviation in brackets) at the level of the... Genetics journals http://www.medworm.com/rss/comments.php?id=3155471 Fri, 08 Jan 2010 22:15:35 +0100 3155471 http://www.medworm.com/index.php?rid=3155470&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F1%2F267%3Frss%3D1 Mammalian coat patterns (e.g., spots, stripes) are hypothesized to play important roles in camouflage and other relevant processes, yet the genetic and developmental bases for these phenotypes are completely unknown. The domestic cat, with its diversity of coat patterns, is an excellent model organism to investigate these phenomena. We have established three independent pedigrees to map the four recognized pattern variants classically considered to be specified by a single locus, Tabby; in order of dominance, these are the unpatterned agouti form called "Abyssinian" or "ticked" (Ta), followed by Spotted (Ts), Mackerel (TM), and Blotched (tb). We demonstrate that at least three different loci control the coat markings of the domestic cat. One locus, responsible for the Abyssinian form (here... Genetics journals http://www.medworm.com/rss/comments.php?id=3155470 Fri, 08 Jan 2010 22:15:35 +0100 3155470 http://www.medworm.com/index.php?rid=3155469&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F1%2F253%3Frss%3D1 Selfish genes, such as meiotic drive elements, propagate themselves through a population without increasing the fitness of host organisms. X-linked (or Y-linked) meiotic drive elements reduce the transmission of the Y (X) chromosome and skew progeny and population sex ratios, leading to intense conflict among genomic compartments. Drosophila simulans is unusual in having a least three distinct systems of X chromosome meiotic drive. Here, we characterize naturally occurring genetic variation at the Winters sex-ratio driver (Distorter on the X or Dox), its progenitor gene (Mother of Dox or MDox), and its suppressor gene (Not Much Yang or Nmy), which have been previously mapped and characterized. We survey three North American populations as well as 13 globally distributed strains and present... Genetics journals http://www.medworm.com/rss/comments.php?id=3155469 Fri, 08 Jan 2010 22:15:35 +0100 3155469 http://www.medworm.com/index.php?rid=3155468&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F1%2F243%3Frss%3D1 Until recently, the use of Bayesian inference was limited to a few cases because for many realistic probability models the likelihood function cannot be calculated analytically. The situation changed with the advent of likelihood-free inference algorithms, often subsumed under the term approximate Bayesian computation (ABC). A key innovation was the use of a postsampling regression adjustment, allowing larger tolerance values and as such shifting computation time to realistic orders of magnitude. Here we propose a reformulation of the regression adjustment in terms of a general linear model (GLM). This allows the integration into the sound theoretical framework of Bayesian statistics and the use of its methods, including model selection via Bayes factors. We then apply the proposed methodo... Genetics journals http://www.medworm.com/rss/comments.php?id=3155468 Fri, 08 Jan 2010 22:15:35 +0100 3155468 http://www.medworm.com/index.php?rid=3155467&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F1%2F233%3Frss%3D1 Most SNPs in the human genome are biallelic; however, there are some sites that are triallelic. We show here that there are approximately twice as many triallelic sites as we would expect by chance. This excess does not appear to be caused by natural selection or mutational hotspots. Instead we propose that a new mutation can induce another mutation either within the same individual or subsequently during recombination. We provide evidence for this model by showing that the rarer two alleles at triallelic sites tend to cluster on phylogenetic trees of human haplotypes. However, we find no association between the density of triallelic sites and the rate of recombination, which leads us to suggest that triallelic sites might be generated by the simultaneous production of two new mutations wi... Genetics journals http://www.medworm.com/rss/comments.php?id=3155467 Fri, 08 Jan 2010 22:15:34 +0100 3155467 http://www.medworm.com/index.php?rid=3155466&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F1%2F221%3Frss%3D1 Evolution at high mutation rates is expected to reduce population fitness deterministically by the accumulation of deleterious mutations. A high enough rate should even cause extinction (lethal mutagenesis), a principle motivating the clinical use of mutagenic drugs to treat viral infections. The impact of a high mutation rate on long-term viral fitness was tested here. A large population of the DNA bacteriophage T7 was grown with a mutagen, producing a genomic rate of 4 nonlethal mutations per generation, two to three orders of magnitude above the baseline rate. Fitness—viral growth rate in the mutagenic environment—was predicted to decline substantially; after 200 generations, fitness had increased, rejecting the model. A high mutation load was nonetheless evident from (i) ma... Genetics journals http://www.medworm.com/rss/comments.php?id=3155466 Fri, 08 Jan 2010 22:15:34 +0100 3155466 http://www.medworm.com/index.php?rid=3155465&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F1%2F213%3Frss%3D1 In this study, we compared a pedigree relatedness method and a relatedness estimator ("molecular relatedness") method using accuracy of estimated breeding values. A commercial data set of common sole, Solea solea, with 51 parents and 1953 offspring ("full data set") was used. Due to missing parents, for 1338 offspring, a pedigree could be reconstructed with 10 microsatellite markers ("reduced data set"). (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=3155465 Fri, 08 Jan 2010 22:15:34 +0100 3155465 http://www.medworm.com/index.php?rid=3155464&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F1%2F199%3Frss%3D1 Generation of an organ of appropriate size and shape requires mechanisms that coordinate growth and patterning, but how this is achieved is not understood. Here we examine the role of the growth regulator dMyc in this process during Drosophila wing imaginal disc development. We find that dMyc is expressed in a dynamic pattern that correlates with fate specification of different regions of the wing disc, leading us to hypothesize that dMyc expression in each region directs its growth. Consistent with this view, clonal analysis of growth in each region demonstrated distinct temporal requirements for dMyc that match its expression. Surprisingly, however, experiments in which dMyc expression is manipulated reveal that the endogenous pattern has only a minor influence on wing shape. Indeed, whe... Genetics journals http://www.medworm.com/rss/comments.php?id=3155464 Fri, 08 Jan 2010 22:15:34 +0100 3155464 http://www.medworm.com/index.php?rid=3155463&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F1%2F185%3Frss%3D1 Members of the Eyes absent (Eya) protein family play important roles in tissue specification and patterning by serving as both transcriptional activators and protein tyrosine phosphatases. These activities are often carried out in the context of complexes containing members of the Six and/or Dach families of DNA binding proteins. eyes absent, the founding member of the Eya family is expressed dynamically within several embryonic, larval, and adult tissues of the fruit fly, Drosophila melanogaster. Loss-of-function mutations are known to result in disruptions of the embryonic head and central nervous system as well as the adult brain and visual system, including the compound eyes. In an effort to understand how eya is regulated during development, we have carried out a genetic screen design... Genetics journals http://www.medworm.com/rss/comments.php?id=3155463 Fri, 08 Jan 2010 22:15:34 +0100 3155463 http://www.medworm.com/index.php?rid=3155462&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F1%2F171%3Frss%3D1 We report here that kcc functions as a K+–Cl– cotransporter when expressed heterologously in Xenopus laevis oocytes: under hypotonic conditions that induce oocyte swelling, oocytes that express Drosophila kcc display robust ion transport activity observed as a Cl–-dependent uptake of the K+ congener 86Rb+. Ectopic, spatially restricted expression of a UAS-kcc+ transgene was used to determine where cotransporter function is required in order to rescue the kccDHS1 BS paralytic phenotype. Interestingly, phenotypic rescue is largely accounted for by targeted, circumscribed expression in the mushroom bodies (MBs) and the ellipsoid body (EB) of the central complex. Intriguingly, we observed that MB induction of kcc+ functioned as a general seizure suppressor in Drosophila. Dros... Genetics journals http://www.medworm.com/rss/comments.php?id=3155462 Fri, 08 Jan 2010 22:15:34 +0100 3155462 http://www.medworm.com/index.php?rid=3155461&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F1%2F155%3Frss%3D1 In this study we present the molecular identification and characterization of F, which acts as the master switch in the housefly pathway. We provide evidence that F corresponds to the transformer ortholog in Musca (Mdtra), which, as a result of alternative processing, expresses functional products only in individuals committed to the female fate. We demonstrate that, once activated, a self-sustaining feedback loop will maintain the female-promoting functions of Mdtra. Absence of Mdtra transcripts in eggs of Arrhenogenic (Ag) mutant females suggests that maternally deployed Mdtra activity initiates this self-sustaining loop in the zygote. When an M factor is paternally transmitted to the zygote, the establishment of the loop is prevented at an early stage before cellularization and splicing... Genetics journals http://www.medworm.com/rss/comments.php?id=3155461 Fri, 08 Jan 2010 22:15:34 +0100 3155461 http://www.medworm.com/index.php?rid=3155460&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F1%2F141%3Frss%3D1 Drosophila translational elongation factor-1 (EF1) interacts in the yeast two-hybrid system with DOA, the LAMMER protein kinase of Drosophila. Analysis of mutant EF1 alleles reveals that the locus encodes a structurally conserved protein essential for both organismal and cellular survival. Although no genetic interactions were detected in combinations with mutations in EF1, an EF1 allele enhanced mutant phenotypes of Doa alleles. A predicted LAMMER kinase phosphorylation site conserved near the C terminus of all EF1 orthologs is a phosphorylation site in vitro for both Drosophila DOA and tobacco PK12 LAMMER kinases. EF1 protein derived from Doa mutant flies migrates with altered mobility on SDS gels, consistent with it being an in vivo substrate of DOA kinase. However, the aberrant mobilit... Genetics journals http://www.medworm.com/rss/comments.php?id=3155460 Fri, 08 Jan 2010 22:15:34 +0100 3155460 http://www.medworm.com/index.php?rid=3155459&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F1%2F129%3Frss%3D1 The wound healing response is an essential mechanism to maintain the integrity of epithelia and protect all organisms from the surrounding milieu. In the "purse-string" mechanism of wound closure, an injured epithelial sheet cinches its hole closed via an intercellular contractile actomyosin cable. This process is conserved across species and utilized by both embryonic as well as adult tissues, but remains poorly understood at the cellular level. In an effort to identify new players involved in purse-string wound closure we developed a wounding strategy suitable for screening large numbers of Drosophila embryos. Using this methodology, we observe wound healing defects in Jun-related antigen (encoding DJUN) and scab (encoding Drosophila PS3 integrin) mutants and performed a forward genetics... Genetics journals http://www.medworm.com/rss/comments.php?id=3155459 Fri, 08 Jan 2010 22:15:34 +0100 3155459 http://www.medworm.com/index.php?rid=3155458&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F1%2F119%3Frss%3D1 Common sequence variants within a gene often generate important differences in expression of corresponding mRNAs. This high level of local (allelic) control—or cis modulation—rivals that produced by gene targeting, but expression is titrated finely over a range of levels. We are interested in exploiting this allelic variation to study gene function and downstream consequences of differences in expression dosage. We have used several bioinformatics and molecular approaches to estimate error rates in the discovery of cis modulation and to analyze some of the biological and technical confounds that contribute to the variation in gene expression profiling. Our analysis of SNPs and alternative transcripts, combined with eQTL maps and selective gene resequencing, revealed that betwee... Genetics journals http://www.medworm.com/rss/comments.php?id=3155458 Fri, 08 Jan 2010 22:15:34 +0100 3155458 http://www.medworm.com/index.php?rid=3155457&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F1%2F107%3Frss%3D1 The Saccharomyces cerevisiae SEN1 gene codes for a nuclear-localized superfamily I helicase. SEN1 is an ortholog of human SETX (senataxin), which has been implicated in the neurological disorders ataxia-ocular apraxia type 2 and juvenile amyotrophic lateral sclerosis. Pleiotropic phenotypes conferred by sen1 mutations suggest that Sen1p affects multiple steps in gene expression. Sen1p is embedded in a protein–protein interaction network involving direct binding to multiple partners. To test whether the interactions occur independently or in a dependent sequence, we examined interactions with the RNA polymerase II subunit Rpb1p, which is required for transcription, and Rnt1p, which is required for 3'-end maturation of many noncoding RNAs. Mutations were identified that impair one of t... Genetics journals http://www.medworm.com/rss/comments.php?id=3155457 Fri, 08 Jan 2010 22:15:34 +0100 3155457 http://www.medworm.com/index.php?rid=3155456&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F1%2F91%3Frss%3D1 The budding yeast Gcn5p is a prototypic histone acetyltransferase controlling transcription of diverse genes. Here we show that Gcn5p is itself regulated by Snf1p and Spt3p. Snf1p likely controls Gcn5p via direct interaction. Mutating four residues in the Gcn5p catalytic domain, T203, S204, T211, and Y212 (TSTY), phenocopies snf1 null cells, including Gcn5p hypophosphorylation, hypoacetylation at the HIS3 promoter, and transcriptional defects of the HIS3 gene. However, overexpressing Snf1p suppresses the above phenotypes associated with the phosphodeficient TSTY mutant, suggesting that it is the interaction with Snf1p important for Gcn5p to activate HIS3. A likely mechanism by which Snf1p potentiates Gcn5p function is to antagonize Spt3p, because the HIS3 expression defects caused by snf1 ... Genetics journals http://www.medworm.com/rss/comments.php?id=3155456 Fri, 08 Jan 2010 22:15:34 +0100 3155456 http://www.medworm.com/index.php?rid=3155455&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F1%2F79%3Frss%3D1 Mutations in the unc-82 locus of Caenorhabditis elegans were previously identified by screening for disrupted muscle cytoskeleton in otherwise apparently normal mutagenized animals. Here we demonstrate that the locus encodes a serine/threonine kinase orthologous to human ARK5/SNARK (NUAK1/NUAK2) and related to the PAR-1 and SNF1/AMP-Activated kinase (AMPK) families. The predicted 1600-amino-acid polypeptide contains an N-terminal catalytic domain and noncomplex repetitive sequence in the remainder of the molecule. Phenotypic analyses indicate that unc-82 is required for maintaining the organization of myosin filaments and internal components of the M-line during cell-shape changes. Mutants exhibit normal patterning of cytoskeletal elements during early embryogenesis. Defects in localizatio... Genetics journals http://www.medworm.com/rss/comments.php?id=3155455 Fri, 08 Jan 2010 22:15:34 +0100 3155455 http://www.medworm.com/index.php?rid=3155454&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F1%2F65%3Frss%3D1 Trinucleotide repeats can form secondary structures, whose inappropriate repair or replication can lead to repeat expansions. There are multiple loci within the human genome where expansion of trinucleotide repeats leads to disease. Although it is known that expanded repeats accumulate double-strand breaks (DSBs), it is not known which DSB repair pathways act on such lesions and whether inaccurate DSB repair pathways contribute to repeat expansions. Using Saccharomyces cerevisiae, we found that CAG/CTG tracts of 70 or 155 repeats exhibited significantly elevated levels of breakage and expansions in strains lacking MRE11, implicating the Mre11/Rad50/Xrs2 complex in repairing lesions at structure-forming repeats. About two-thirds of the expansions that occurred in the absence of MRE11 were d... Genetics journals http://www.medworm.com/rss/comments.php?id=3155454 Fri, 08 Jan 2010 22:15:34 +0100 3155454 http://www.medworm.com/index.php?rid=3155453&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F1%2F53%3Frss%3D1 Active endogenous transposable elements, useful tools for gene isolation, have not been reported from any legume species. An active transposable element was suggested to reside in the W4 locus that governs flower color in soybean. Through biochemical and molecular analyses of several revertants of the w4-m allele, we have shown that the W4 locus encodes dihydroflavonol-4-reductase 2 (DFR2). w4-m has arisen through insertion of Tgm9, a 20,548-bp CACTA-like transposable element, into the second intron of DFR2. Tgm9 showed high nucleic acid sequence identity to Tgmt*. Its 5' and 3' terminal inverted repeats start with conserved CACTA sequence. The 3' subterminal region is highly repetitive. Tgm9 carries TNP1- and TNP2-like transposase genes that are expressed in the mutable line, T322 (w4-m).... Genetics journals http://www.medworm.com/rss/comments.php?id=3155453 Fri, 08 Jan 2010 22:15:34 +0100 3155453 http://www.medworm.com/index.php?rid=3155452&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F1%2F43%3Frss%3D1 The DNA-packaging specificities of phages and 21 depend on the specific DNA interactions of the small terminase subunits, which have support helix-turn-recognition helix-wing DNA-binding motifs. -Terminase with the recognition helix of 21 preferentially packages 21 DNA. This chimeric terminase's ability to package DNA is reduced ~20-fold. Phage with the chimeric terminase is unable to form plaques, but pseudorevertants are readily obtained. Some pseudorevertants have trans-acting suppressors that change codons of the recognition helix. Some of these codons appear to remove an unfavorable base-pair contact; others appear to create a novel nonspecific DNA contact. Helper-packaging experiments show that these mutant terminases have lost the ability to discriminate between and 21 during DNA pa... Genetics journals http://www.medworm.com/rss/comments.php?id=3155452 Fri, 08 Jan 2010 22:15:34 +0100 3155452 http://www.medworm.com/index.php?rid=3155451&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F1%2F27%3Frss%3D1 Translesion synthesis DNA polymerases contribute to DNA damage tolerance by mediating replication of damaged templates. Due to the low fidelity of these enzymes, lesion bypass is often mutagenic. We have previously shown that, in Saccharomyces cerevisiae, the contribution of the error-prone DNA polymerase (Pol) to replication and mutagenesis is greatly enhanced if the normal replisome is defective due to mutations in replication genes. Here we present evidence that this defective-replisome-induced mutagenesis (DRIM) results from the participation of Pol in the copying of undamaged DNA rather than from mutagenic lesion bypass. First, DRIM is not elevated in strains that have a high level of endogenous DNA lesions due to defects in nucleotide excision repair or base excision repair pathways.... Genetics journals http://www.medworm.com/rss/comments.php?id=3155451 Fri, 08 Jan 2010 22:15:34 +0100 3155451 http://www.medworm.com/index.php?rid=3155450&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F1%2F19%3Frss%3D1 Advances in next-generation sequencing technology have facilitated the discovery of single nucleotide polymorphisms (SNPs). Sequenom-based SNP-typing assays were developed for 1359 maize SNPs identified via comparative next-generation transcriptomic sequencing. Approximately 75% of these SNPs were successfully converted into genetic markers that can be scored reliably and used to generate a SNP-based genetic map by genotyping recombinant inbred lines from the intermated B73 x Mo17 population. The quantitative nature of Sequenom-based SNP assays led to the development of a time- and cost-efficient strategy to genetically map mutants via quantitative bulked segregant analysis. This strategy was used to rapidly map the loci associated with several dozen recessive mutants. Because a mutant can... Genetics journals http://www.medworm.com/rss/comments.php?id=3155450 Fri, 08 Jan 2010 22:15:34 +0100 3155450 http://www.medworm.com/index.php?rid=3155449&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F1%2F9%3Frss%3D1 The emergence of recombinant DNA technology occurred via the appropriation of known tools and procedures in novel ways that had broad applications for analyzing and modifying gene structure and organization of complex genomes. Although revolutionary in their impact, the tools and procedures per se were not revolutionary. Rather, the novel ways in which they were applied was what transformed biology. (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=3155449 Fri, 08 Jan 2010 22:15:34 +0100 3155449 http://www.medworm.com/index.php?rid=3155448&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F1%2F3%3Frss%3D1 In January 1910, a century ago, Thomas Hunt Morgan discovered his first Drosophila mutant, a white-eyed male (Morgan 1910). Morgan named the mutant gene white and soon demonstrated that it resided on the X chromosome. This was the first localization of a specific gene to a particular chromosome. Thus began Drosophila experimental genetics. The story of the initial work on white is well known but what is less well appreciated is the multiplicity of ways in which this gene has been used to explore fundamental questions in genetics. Here, I review some of the highlights of a century's productive use of white in Drosophila genetics. (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=3155448 Fri, 08 Jan 2010 22:15:34 +0100 3155448 http://www.medworm.com/index.php?rid=3155447&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F1%2F1%3Frss%3D1 (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=3155447 Fri, 08 Jan 2010 22:15:34 +0100 3155447 http://www.medworm.com/index.php?rid=3155446&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F184%2F1%2FNP%3Frss%3D1 (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=3155446 Fri, 08 Jan 2010 22:15:34 +0100 3155446 http://www.medworm.com/index.php?rid=3070156&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1601%3Frss%3D1 (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=3070156 Tue, 08 Dec 2009 20:05:16 +0100 3070156 http://www.medworm.com/index.php?rid=3070155&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1597%3Frss%3D1 The correlation coefficient is commonly used as a measure of the divergence of gene expression profiles between different species. Here we point out a potential problem with this statistic: if measurement error is large relative to the differences in expression, the correlation coefficient will tend to show high divergence for genes that have relatively uniform levels of expression across tissues or time points. We show that genes with a conserved uniform pattern of expression have significantly higher levels of expression divergence, when measured using the correlation coefficient, than other genes, in a data set from mouse, rat, and human. We also show that the Euclidean distance yields low estimates of expression divergence for genes with a conserved uniform pattern of expression. (Sour... Genetics journals http://www.medworm.com/rss/comments.php?id=3070155 Tue, 08 Dec 2009 20:05:16 +0100 3070155 http://www.medworm.com/index.php?rid=3070154&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1591%3Frss%3D1 Phosphorylation of the Ndc80 kinetochore protein by the Ipl1/Aurora B kinase reduces its microtubule binding activity in vitro. We found that kinetochore-bound Ndc80 is phosphorylated on Ipl1 sites in vivo, but this phosphorylation is not essential. Instead, we show that additional Ipl1 targets contribute to segregation and the spindle checkpoint. (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=3070154 Tue, 08 Dec 2009 20:05:16 +0100 3070154 http://www.medworm.com/index.php?rid=3070153&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1575%3Frss%3D1 Doubly uniparental inheritance (DUI) of mitochondrial DNA in marine mussels (Mytiloida), freshwater mussels (Unionoida), and marine clams (Veneroida) is the only known exception to the general rule of strict maternal transmission of mtDNA in animals. DUI is characterized by the presence of gender-associated mitochondrial DNA lineages that are inherited through males (male-transmitted or M types) or females (female-transmitted or F types), respectively. This unusual system constitutes an excellent model for studying basic aspects of mitochondrial DNA inheritance and the evolution of mtDNA genomes in general. Here we compare published mitochondrial genomes of unionoid bivalve species with DUI, with an emphasis on characterizing unassigned regions, to identify regions of the F and M mtDNA gen... Genetics journals http://www.medworm.com/rss/comments.php?id=3070153 Tue, 08 Dec 2009 20:05:15 +0100 3070153 http://www.medworm.com/index.php?rid=3070152&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1565%3Frss%3D1 Insertional mutagenesis screens play an integral part in the annotating of functional data for all sequenced genes in the postgenomic era. Chemical mutagenesis screens are highly efficient but identifying the causative gene can be a laborious task. Other mutagenesis platforms, such as transposable elements, have been successfully applied for insertional mutagenesis screens in both the mouse and rat. However, relatively low transposition efficiency has hampered their use as a high-throughput forward genetic mutagenesis screen. Here we report the first evidence of germline activity in the mouse using a naturally active DNA transposon derived from the medaka fish called Tol2, as an alternative system for high-throughput forward genetic mutagenesis screening tool. (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=3070152 Tue, 08 Dec 2009 20:05:15 +0100 3070152 http://www.medworm.com/index.php?rid=3070151&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1555%3Frss%3D1 This study was performed in near-isogenic material derived from a cross between the day-neutral European flint inbred line FV286 and the tropical short-day inbred line FV331. Recombinant individuals were identified among a large segregating population and their progenies were scored for flowering time. Combined genotypic characterization led to delimit the QTL to an interval of 170 kb and highlighted an unbalanced recombination pattern. Two bacterial artificial chromosomes (BACs) covering the region were analyzed to identify putative candidate genes, and synteny with rice, sorghum, and brachypodium was investigated. A gene encoding a CCT domain protein homologous to the rice Ghd7 heading date regulator was identified, but its causative role was not demonstrated and deserves further analyse... Genetics journals http://www.medworm.com/rss/comments.php?id=3070151 Tue, 08 Dec 2009 20:05:15 +0100 3070151 http://www.medworm.com/index.php?rid=3070150&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1545%3Frss%3D1 Genomic prediction of future phenotypes or genetic merit using dense SNP genotypes can be used for prediction of disease risk, forensics, and genomic selection of livestock and domesticated plant species. The reliability of genomic predictions is their squared correlation with the true genetic merit and indicates the proportion of the genetic variance that is explained. As reliability relies heavily on the number of phenotypes, combining data sets from multiple populations may be attractive as a way to increase reliabilities, particularly when phenotypes are scarce. However, this strategy may also decrease reliabilities if the marker effects are very different between the populations. The effect of combining multiple populations on the reliability of genomic predictions was assessed for tw... Genetics journals http://www.medworm.com/rss/comments.php?id=3070150 Tue, 08 Dec 2009 20:05:15 +0100 3070150 http://www.medworm.com/index.php?rid=3070149&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1535%3Frss%3D1 Innate immunity is the first line of defense against microbial infections. Although polymorphisms in toll-like receptors (TLRs) and downstream signaling molecules (CD14, TLR2, TLR4, TLR5, and IRAK4) affect the innate immune response, these variants account for only a portion of the ability of the host to respond to bacteria, fungi, and viruses. To identify other genes involved in the innate immune response, we challenged 16 inbred murine strains with lipopolysaccharide (LPS) systemically and measured serum concentrations of pro-inflammatory cytokines IL-1β, IL-6, and TNF, and the chemokine KC 6 hr post-treatment. Loci that segregate with strain phenotypes were identified by whole genome association (WGA) mapping of cytokine concentrations. Published gene expression profiles and quanti... Genetics journals http://www.medworm.com/rss/comments.php?id=3070149 Tue, 08 Dec 2009 20:05:15 +0100 3070149 http://www.medworm.com/index.php?rid=3070148&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1525%3Frss%3D1 The objectives of my research were to (i) investigate by computer simulations the power and type I error rate for detecting quantitative trait loci (QTL) with additive effects using recombinant inbred line (RIL) populations of maize derived from various mating designs, (ii) compare these estimates to those obtained for RIL populations of Arabidopsis thaliana, (iii) examine for both species the optimum number of inbreds used as parents of the NAM populations, and (iv) provide on the basis of the results of these two model species a general guideline for the design of NAM populations in other plant species. The computer simulations were based on empirical data of a set of 26 diverse maize inbred lines and a set of 20 A. thaliana inbreds both representing a large part of the genetic diversity... Genetics journals http://www.medworm.com/rss/comments.php?id=3070148 Tue, 08 Dec 2009 20:05:15 +0100 3070148 http://www.medworm.com/index.php?rid=3070147&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1507%3Frss%3D1 Under drought, substantial genotype–environment (G x E) interactions impede breeding progress for yield. Identifying genetic controls associated with yield response is confounded by poor genetic correlations across testing environments. Part of this problem is related to our inability to account for the interplay of genetic controls, physiological traits, and environmental conditions throughout the crop cycle. We propose a modeling approach to bridge this "gene-to-phenotype" gap. For maize under drought, we simulated the impact of quantitative trait loci (QTL) controlling two key processes (leaf and silk elongation) that influence crop growth, water use, and grain yield. Substantial G x E interaction for yield was simulated for hypothetical recombinant inbred lines (RILs) across diff... Genetics journals http://www.medworm.com/rss/comments.php?id=3070147 Tue, 08 Dec 2009 20:05:15 +0100 3070147 http://www.medworm.com/index.php?rid=3070146&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1493%3Frss%3D1 Codon usage bias (CUB) has been documented across a wide range of taxa and is the subject of numerous studies. While most explanations of CUB invoke some type of natural selection, most measures of CUB adaptation are heuristically defined. In contrast, we present a novel and mechanistic method for defining and contextualizing CUB adaptation to reduce the cost of nonsense errors during protein translation. Using a model of protein translation, we develop a general approach for measuring the protein production cost in the face of nonsense errors of a given allele as well as the mean and variance of these costs across its coding synonyms. We then use these results to define the nonsense error adaptation index (NAI) of the allele or a contiguous subset thereof. Conceptually, the NAI value of a... Genetics journals http://www.medworm.com/rss/comments.php?id=3070146 Tue, 08 Dec 2009 20:05:15 +0100 3070146 http://www.medworm.com/index.php?rid=3070145&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1477%3Frss%3D1 This study quantifies the effects of naturally occurring X-linked variation on immune response in Drosophila melanogaster to assess associations between immunity genotypes and innate immune response. We constructed a set of 168 X-chromosomal extraction lines, incorporating X chromosomes from a natural population into co-isogenic autosomal backgrounds, and genotyped the lines at 88 SNPs in 20 X-linked immune genes. We find that genetic variation in many of the genes is associated with immune response phenotypes, including bacterial load and immune gene expression. Many of the associations act in a sex-specific or sexually antagonistic manner, supporting the theory that with the selective pressures facing genes on the X chromosome, sexually antagonistic variation may be more easily maintaine... Genetics journals http://www.medworm.com/rss/comments.php?id=3070145 Tue, 08 Dec 2009 20:05:15 +0100 3070145 http://www.medworm.com/index.php?rid=3070144&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1453%3Frss%3D1 We consider a population that adapts to a gradually changing environment. Our aim is to describe how ecological and genetic factors combine to determine the genetic basis of adaptation. Specifically, we consider the evolution of a polygenic trait that is under stabilizing selection with a moving optimum. The ecological dynamics are defined by the strength of selection, tilde;, and the speed of the optimum, v; the key genetic parameters are the mutation rate and the variance of the effects of new mutations, . We develop analytical approximations within an "adaptive-walk" framework and describe how selection acts as a sieve that transforms a given distribution of new mutations into the distribution of adaptive substitutions. Our analytical results are complemented by individual-based simulat... Genetics journals http://www.medworm.com/rss/comments.php?id=3070144 Tue, 08 Dec 2009 20:05:15 +0100 3070144 http://www.medworm.com/index.php?rid=3070143&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1443%3Frss%3D1 Sex determination in fish is a labile character in evolutionary terms. The sex-determining (SD) master gene can differ even between closely related fish species. This group is an interesting model for studying the evolution of the SD region and the gonadal differentiation pathway. The turbot (Scophthalmus maximus) is a flatfish of great commercial value, where a strong sexual dimorphism exists for growth rate. Following a QTL and marker association approach in five families and a natural population, we identified the main SD region of turbot at the proximal end of linkage group (LG) 5, close to the SmaUSC-E30 marker. The refined map of this region suggested that this marker would be 2.6 cM and 1.4 Mb from the putative SD gene. This region appeared mostly undifferentiated between males and ... Genetics journals http://www.medworm.com/rss/comments.php?id=3070143 Tue, 08 Dec 2009 20:05:15 +0100 3070143 http://www.medworm.com/index.php?rid=3070142&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1431%3Frss%3D1 Exact conditional tests are often required to evaluate statistically whether a sample of diploids comes from a population with Hardy–Weinberg proportions or to confirm the accuracy of genotype assignments. This requirement is especially common when the sample includes multiple alleles and sparse data, thus rendering asymptotic methods, such as the common 2-test, unreliable. Such an exact test can be performed using the likelihood ratio as its test statistic rather than the more commonly used probability test. Conceptual advantages in using the likelihood ratio are discussed. A substantially improved algorithm is described to permit the performance of a full-enumeration exact test on sample sizes that are too large for previous methods. An improved Monte Carlo algorithm is also propos... Genetics journals http://www.medworm.com/rss/comments.php?id=3070142 Tue, 08 Dec 2009 20:05:15 +0100 3070142 http://www.medworm.com/index.php?rid=3070141&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1421%3Frss%3D1 We present a formalism for unifying the inference of population size from genetic sequences and mathematical models of infectious disease in populations. Virus phylogenies have been used in many recent studies to infer properties of epidemics. These approaches rely on coalescent models that may not be appropriate for infectious diseases. We account for phylogenetic patterns of viruses in susceptible–infected (SI), susceptible–infected–susceptible (SIS), and susceptible–infected–recovered (SIR) models of infectious disease, and our approach may be a viable alternative to demographic models used to reconstruct epidemic dynamics. The method allows epidemiological parameters, such as the reproductive number, to be estimated directly from viral sequence data. We al... Genetics journals http://www.medworm.com/rss/comments.php?id=3070141 Tue, 08 Dec 2009 20:05:15 +0100 3070141 http://www.medworm.com/index.php?rid=3070140&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1397%3Frss%3D1 P granules are non-membrane-bound organelles found in the germ-line cytoplasm throughout Caenorhabditis elegans development. Like their "germ granule" counterparts in other animals, P granules are thought to act as determinants of the identity and special properties of germ cells, properties that include the unique ability to give rise to all tissues of future generations of an organism. Therefore, understanding how P granules work is critical to understanding how cellular immortality and totipotency are retained, gained, and lost. Here we report on a genomewide RNAi screen in C. elegans, which identified 173 genes that affect the stability, localization, and function of P granules. Many of these genes fall into specific classes with shared P-granule phenotypes, allowing us to better under... Genetics journals http://www.medworm.com/rss/comments.php?id=3070140 Tue, 08 Dec 2009 20:05:15 +0100 3070140 http://www.medworm.com/index.php?rid=3070139&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1385%3Frss%3D1 The African fish Nothobranchius furzeri is the shortest-lived vertebrate species that can reproduce in captivity, with a median life span of 9–11 weeks for the shortest-lived strain. Natural populations of N. furzeri display differences in life span, aging biomarkers, behavior, and color, which make N. furzeri a unique vertebrate system for studying the genetic basis of these traits. We mapped regions of the genome involved in sex determination and tail color by genotyping microsatellite markers in the F2 progeny of a cross between a short-lived, yellow-tailed strain and a long-lived, red-tailed strain of N. furzeri. We identified one region linked with the yellow/red tail color that maps close to melanocortin 1 receptor (mc1r), a gene involved in pigmentation in several vertebrate s... Genetics journals http://www.medworm.com/rss/comments.php?id=3070139 Tue, 08 Dec 2009 20:05:15 +0100 3070139 http://www.medworm.com/index.php?rid=3070138&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1373%3Frss%3D1 Enhanced stress response has been suggested to promote longevity in many species. Calorie restriction (CR) and conserved nutrient-sensing target of rapamycin (TOR) and protein kinase A (PKA) pathways have also been suggested to extend life span by increasing stress response, which protects cells from age-dependent accumulation of oxidative damages. Here we show that deleting the yeast 14-3-3 protein, Bmh1, extends chronological life span (CLS) by activating the stress response. 14-3-3 proteins are highly conserved chaperone-like proteins that play important roles in many cellular processes. bmh1-induced heat resistance and CLS extension require the general stress-response transcription factors Msn2, Msn4, and Rim15. The bmh1 mutant also displays a decreased reactive oxygen species level an... Genetics journals http://www.medworm.com/rss/comments.php?id=3070138 Tue, 08 Dec 2009 20:05:15 +0100 3070138 http://www.medworm.com/index.php?rid=3070137&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1357%3Frss%3D1 The nerve-cell cytoskeleton is essential for the regulation of intrinsic neuronal activity. For example, neuronal migration defects are associated with microtubule regulators, such as LIS1 and dynein, as well as with actin regulators, including Rac GTPases and integrins, and have been thought to underlie epileptic seizures in patients with cortical malformations. However, it is plausible that post-developmental functions of specific cytoskeletal regulators contribute to the more transient nature of aberrant neuronal activity and could be masked by developmental anomalies. Accordingly, our previous results have illuminated functional roles, distinct from developmental contributions, for Caenorhabditis elegans orthologs of LIS1 and dynein in GABAergic synaptic vesicle transport. Here, we rep... Genetics journals http://www.medworm.com/rss/comments.php?id=3070137 Tue, 08 Dec 2009 20:05:15 +0100 3070137 http://www.medworm.com/index.php?rid=3070136&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1341%3Frss%3D1 Ammonium channels, called Amt or Mep, concentrate NH4+ against a gradient. Each monomer of the trimer has a pore through which substrate passes and a C-terminal cytoplasmic extension. The importance of the C-terminal extension to AmtB activity remains unclear. We have described lesions in conserved C-terminal residues that inactivate AmtB and here characterize 38 intragenic suppressors upstream of the C terminus (~1/3 of total suppressors). Three that occurred repeatedly, including the previously characterized W148L at the pore entry, restored growth at low NH3 to nearly wild-type levels and hence restored high activity. V116L completely restored function to two of the mutant proteins and, when separated from other lesions, did not damage wild-type AmtB. A179E notably altered folding of Am... Genetics journals http://www.medworm.com/rss/comments.php?id=3070136 Tue, 08 Dec 2009 20:05:15 +0100 3070136 http://www.medworm.com/index.php?rid=3070135&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1327%3Frss%3D1 The Escherichia coli ammonium channel AmtB is a trimer in which each monomer carries a pore for substrate conduction and a cytoplasmic C-terminal extension of ~25 residues. Deletion of the entire extension leaves the protein with intermediate activity, but some smaller lesions in this region completely inactivate AmtB, as do some lesions in its cytoplasmic loops. We here provide genetic evidence that inactivation depends on the essential protease HflB, which appears to cause inactivation not as a protease but as a chaperone. Selection for restored function of AmtB is a positive selection for loss of the ATPase/chaperone activity of HflB and reveals that the conditional lethal phenotype for hflB is cold sensitivity. Deletion of only a few residues from the C terminus of damaged AmtB protein... Genetics journals http://www.medworm.com/rss/comments.php?id=3070135 Tue, 08 Dec 2009 20:05:15 +0100 3070135 http://www.medworm.com/index.php?rid=3070134&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1315%3Frss%3D1 The race-specific resistance gene Pi-ta has been effectively used to control blast disease, one of the most destructive plant diseases worldwide. A single amino acid change at the 918 position of the Pi-ta protein was known to determine resistance specificity. To understand the evolutionary dynamics present, we examined sequences of the Pi-ta locus and its flanking regions in 159 accessions composed of seven AA genome Oryza species: O. sativa, O. rufipogon, O. nivara, O. meridionalis, O. glaberrima, O. barthii, and O. glumaepatula. A 3364-bp fragment encoding a predicted transposon was found in the proximity of the Pi-ta promoter region associated with the resistance phenotype. Haplotype network analysis with 33 newly identified Pi-ta haplotypes and 18 newly identified Pi-ta protein varian... Genetics journals http://www.medworm.com/rss/comments.php?id=3070134 Tue, 08 Dec 2009 20:05:15 +0100 3070134 http://www.medworm.com/index.php?rid=3070133&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1297%3Frss%3D1 Short interfering RNAs (siRNAs) are a class of regulatory effectors that enforce gene silencing through formation of RNA duplexes. Although progress has been made in identifying the capabilities of siRNAs in silencing foreign RNA and transposable elements, siRNA functions in endogenous gene regulation have remained mysterious. In certain organisms, siRNA biosynthesis involves novel enzymes that act as RNA-directed RNA polymerases (RdRPs). Here we analyze the function of a Caenorhabditis elegans RdRP, RRF-3, during spermatogenesis. We found that loss of RRF-3 function resulted in pleiotropic defects in sperm development and that sperm defects led to embryonic lethality. Notably, sperm nuclei in mutants of either rrf-3 or another component of the siRNA pathway, eri-1, were frequently surroun... Genetics journals http://www.medworm.com/rss/comments.php?id=3070133 Tue, 08 Dec 2009 20:05:15 +0100 3070133 http://www.medworm.com/index.php?rid=3070132&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1283%3Frss%3D1 Small regulatory RNAs are key regulators of gene expression. One class of small regulatory RNAs, termed the endogenous small interfering RNAs (endo siRNAs), is thought to negatively regulate cellular transcripts via an RNA interference (RNAi)-like mechanism termed endogenous RNAi (endo RNAi). A complex of proteins composed of ERI-1/3/5, RRF-3, and DICER (the ERI/DICER complex) mediates endo RNAi processes in Caenorhabditis elegans. We conducted a genetic screen to identify additional components of the endo RNAi machinery. Our screen recovered alleles of eri-9, which encodes a novel DICER-interacting protein, and a missense mutation within the helicase domain of DICER [DCR-1(G492R)]. ERI-9(–) and DCR-1(G492) animals exhibit defects in endo siRNA expression and a concomitant failure to... Genetics journals http://www.medworm.com/rss/comments.php?id=3070132 Tue, 08 Dec 2009 20:05:14 +0100 3070132 http://www.medworm.com/index.php?rid=3070131&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1269%3Frss%3D1 Cdc7-Dbf4 is a two-subunit kinase required for initiating DNA replication. The Dbf4 regulatory subunit is required for Cdc7 kinase activity. Previous studies have shown that the C termini of Dbf4 orthologs encode a single (putative) C2H2 zinc (Zn) finger, referred to as "motif C." By mutational analysis we show that the Zn finger is not required for the essential function of Dbf4. However, deletion and point mutants altering conserved Zn-finger residues exhibit a substantially slowed S-phase, DNA damage sensitivity, and a hypo-mutagenic phenotype following UV irradiation. Using two-hybrid and biochemical assays, we show that the Dbf4 Zn finger interacts with Cdc7 and stimulates its kinase activity. However, a separable Dbf4 region also mediates an interaction with Cdc7 such that only the l... Genetics journals http://www.medworm.com/rss/comments.php?id=3070131 Tue, 08 Dec 2009 20:05:14 +0100 3070131 http://www.medworm.com/index.php?rid=3070130&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1261%3Frss%3D1 The plant mitochondrial genome is recombinogenic, with DNA exchange activity controlled to a large extent by nuclear gene products. One nuclear gene, MSH1, appears to participate in suppressing recombination in Arabidopsis at every repeated sequence ranging in size from 108 to 556 bp. Present in a wide range of plant species, these mitochondrial repeats display evidence of successful asymmetric DNA exchange in Arabidopsis when MSH1 is disrupted. Recombination frequency appears to be influenced by repeat sequence homology and size, with larger size repeats corresponding to increased DNA exchange activity. The extensive mitochondrial genomic reorganization of the msh1 mutant produced altered mitochondrial transcription patterns. Comparison of mitochondrial genomes from the Arabidopsis ecotyp... Genetics journals http://www.medworm.com/rss/comments.php?id=3070130 Tue, 08 Dec 2009 20:05:14 +0100 3070130 http://www.medworm.com/index.php?rid=3070129&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1249%3Frss%3D1 Yeast replication checkpoint mutants lose viability following transient exposure to hydroxyurea, a replication-impeding drug. In an effort to understand the basis for this lethality, we discovered that different events are responsible for inviability in checkpoint-deficient cells harboring mutations in the mec1 and rad53 genes. By monitoring genomewide replication dynamics of cells exposed to hydroxyurea, we show that cells with a checkpoint deficient allele of RAD53, rad53K227A, fail to duplicate centromeres. Following removal of the drug, however, rad53K227A cells recover substantial DNA replication, including replication through centromeres. Despite this recovery, the rad53K227A mutant fails to achieve biorientation of sister centromeres during recovery from hydroxyurea, leading to seco... Genetics journals http://www.medworm.com/rss/comments.php?id=3070129 Tue, 08 Dec 2009 20:05:14 +0100 3070129 http://www.medworm.com/index.php?rid=3070128&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1235%3Frss%3D1 Centromeres, because of their repeat structure and lack of sequence conservation, are difficult to assemble and compare across organisms. It was recently discovered that rice centromeres often contain genes. This suggested a method for studying centromere homologies between wheat and rice chromosomes by mapping rice centromeric genes onto wheat aneuploid stocks. Three of the seven cDNA clones of centromeric genes from rice centromere 8 (Cen8), 6729.t09, 6729.t10, and 6730.t11 which lie in the Cen8 kinetochore region, and three wheat ESTs, BJ301191, BJ305475, and BJ280500, with similarity to sequences of rice centromeric genes, were mapped to the centromeric regions of the wheat group-7 (W7) chromosomes. A possible pericentric inversion in chromosome 7D was detected. Genomewide comparison o... Genetics journals http://www.medworm.com/rss/comments.php?id=3070128 Tue, 08 Dec 2009 20:05:14 +0100 3070128 http://www.medworm.com/index.php?rid=3070127&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1227%3Frss%3D1 The bal defect in the Arabidopsis thaliana Columbia strain was spontaneously generated in an inbred ddm1 (decrease in DNA methylation 1) mutant background in which various genetic and epigenetic alterations accumulate. The bal variant displays short stature and curled leaves due to the constitutive activation of defense signaling. These bal phenotypes are metastable and phenotypic suppression is evident in more than one-third of ethyl methanesulfonate (EMS)-treated bal M1 plants. The semidominant bal allele maps to the RPP5 (recognition of Peronospora parasitica 5) locus, which includes a cluster of disease Resistance (R) genes, many of which show an increase in steady-state expression levels in the bal variant. Here, we report that activation of RPP5 locus R genes and dwarfing in the bal ... Genetics journals http://www.medworm.com/rss/comments.php?id=3070127 Tue, 08 Dec 2009 20:05:14 +0100 3070127 http://www.medworm.com/index.php?rid=3070126&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1215%3Frss%3D1 Digestion–ligation–amplification (DLA), a novel adaptor-mediated PCR-based method that uses a single-stranded oligo as the adaptor, was developed to overcome difficulties of amplifying unknown sequences flanking known DNA sequences in large genomes. DLA specifically overcomes the problems associated with existing methods for amplifying genomic sequences flanking Mu transposons, including high levels of nonspecific amplification. Two DLA-based strategies, MuClone and DLA-454, were developed to isolate Mu-tagged alleles. MuClone allows for the amplification of subsets of the numerous Mu transposons in the genome, using unique three-nucleotide tags at the 3' ends of primers, simplifying the identification of flanking sequences that cosegregate with mutant phenotypes caused by Mu i... Genetics journals http://www.medworm.com/rss/comments.php?id=3070126 Tue, 08 Dec 2009 20:05:14 +0100 3070126 http://www.medworm.com/index.php?rid=3070125&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1205%3Frss%3D1 A career of following unplanned observations has serendipitously led to a deep appreciation of the capacity that bacterial cells have for restructuring their genomes in a biologically responsive manner. Routine characterization of spontaneous mutations in the gal operon guided the discovery that bacteria transpose DNA segments into new genome sites. A failed project to fuse sequences to a lacZ reporter ultimately made it possible to demonstrate how readily Escherichia coli generated rearrangements necessary for in vivo cloning of chromosomal fragments into phage genomes. Thinking about the molecular mechanism of IS1 and phage Mu transposition unexpectedly clarified how transposable elements mediate large-scale rearrangements of the bacterial genome. Following up on lab lore about long dela... Genetics journals http://www.medworm.com/rss/comments.php?id=3070125 Tue, 08 Dec 2009 20:05:14 +0100 3070125 http://www.medworm.com/index.php?rid=3070124&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2F1203%3Frss%3D1 (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=3070124 Tue, 08 Dec 2009 20:05:14 +0100 3070124 http://www.medworm.com/index.php?rid=3070123&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F4%2FNP%3Frss%3D1 (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=3070123 Tue, 08 Dec 2009 20:05:14 +0100 3070123 http://www.medworm.com/index.php?rid=3007041&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F1201%3Frss%3D1 (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=3007041 Wed, 18 Nov 2009 16:39:31 +0100 3007041 http://www.medworm.com/index.php?rid=3007040&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F1195%3Frss%3D1 Mei4 is a key sporulation-specific transcription factor in fission yeast. Ectopic expression of Mei4 in vegetative cells caused formation of nucleated membranous compartments, which shared common features with normal forespore membranes, thereby perturbing nuclear division. These results suggest why expression of development-specific transcription factors must be strictly controlled. (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=3007040 Wed, 18 Nov 2009 16:39:31 +0100 3007040 http://www.medworm.com/index.php?rid=3007039&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F1187%3Frss%3D1 Transposable elements are frequently used in Drosophila melanogaster for imprecise excision screens to delete genes of interest. However, these screens are highly variable in the number and size of deletions that are recovered. Here, we show that conducting excision screens in mus309 mutant flies that lack DmBlm, the Drosophila ortholog of the Bloom syndrome protein, increases the percentage and overall size of flanking deletions recovered after excision of either P or Minos elements. (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=3007039 Wed, 18 Nov 2009 16:39:31 +0100 3007039 http://www.medworm.com/index.php?rid=3007038&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F1175%3Frss%3D1 Sexual dimorphism in morphological, physiological, and behavioral traits is pervasive in animals, as is the observation of strong sexual dimorphism in genomewide patterns of gene expression in the few species where this has been studied. Studies of transcriptome divergence show that most interspecific transcriptional divergence is highly sex dependent, an observation consistent with the action of sex-dependent natural selection during species divergence. However, few transcriptome evolution studies have been conducted between recently diverged species (<1 MY). Here, we present analyses of sex-biased transcriptome divergence in sexually mature adults of three recently diverged species of Drosophila: Drosophila pseudoobscura, D. persimilis, and D. pseudoobscura bogotana. Data were collect... Genetics journals http://www.medworm.com/rss/comments.php?id=3007038 Wed, 18 Nov 2009 16:39:31 +0100 3007038 http://www.medworm.com/index.php?rid=3007037&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F1165%3Frss%3D1 RNAi-mediated gene knockdown in Drosophila melanogaster is a powerful method to analyze loss-of-function phenotypes both in cell culture and in vivo. However, it has also become clear that false positives caused by off-target effects are prevalent, requiring careful validation of RNAi-induced phenotypes. The most rigorous proof that an RNAi-induced phenotype is due to loss of its intended target is to rescue the phenotype by a transgene impervious to RNAi. For large-scale validations in the mouse and Caenorhabditis elegans, this has been accomplished by using bacterial artificial chromosomes (BACs) of related species. However, in Drosophila, this approach is not feasible because transformation of large BACs is inefficient. We have therefore developed a general RNAi rescue approach for Dros... Genetics journals http://www.medworm.com/rss/comments.php?id=3007037 Wed, 18 Nov 2009 16:39:31 +0100 3007037 http://www.medworm.com/index.php?rid=3007036&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F1153%3Frss%3D1 This study demonstrates the potential to reveal functional polymorphisms underlying quantitative traits in low LD populations. (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=3007036 Wed, 18 Nov 2009 16:39:31 +0100 3007036 http://www.medworm.com/index.php?rid=3007035&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F1141%3Frss%3D1 Effective pharmacological therapy is often inhibited by variable drug responses and adverse drug reactions. Dissecting the molecular basis of different drug responses is difficult due to complex interactions involving multiple genes, pathways, and cellular processes. We previously found a single nucleotide polymorphism within cystathionine β-synthase (CYS4) that causes multi-drug sensitivity in a vineyard strain of Saccharomyces cerevisiae. However, not all variation was accounted for by CYS4. To identify additional genes influencing drug sensitivity, we used CYS4 as a covariate and conducted both single- and combined-cross linkage mapping. After eliminating numerous false-positive associations, we identified 16 drug-sensitivity loci, only 3 of which had been previously identified. Of... Genetics journals http://www.medworm.com/rss/comments.php?id=3007035 Wed, 18 Nov 2009 16:39:31 +0100 3007035 http://www.medworm.com/index.php?rid=3007034&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F1127%3Frss%3D1 The combination of QTL mapping studies of synthetic lines and association mapping studies of natural diversity represents an opportunity to throw light on the genetically based variation of quantitative traits. With the positional information provided through quantitative trait locus (QTL) mapping, which often leads to wide intervals encompassing numerous genes, it is now feasible to directly target candidate genes that are likely to be responsible for the observed variation in completely sequenced genomes and to test their effects through association genetics. This approach was performed in grape, a newly sequenced genome, to decipher the genetic architecture of anthocyanin content. Grapes may be either white or colored, ranging from the lightest pink to the darkest purple tones according... Genetics journals http://www.medworm.com/rss/comments.php?id=3007034 Wed, 18 Nov 2009 16:39:31 +0100 3007034 http://www.medworm.com/index.php?rid=3007033&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F1119%3Frss%3D1 Genomic Selection (GS) is a newly developed tool for the estimation of breeding values for quantitative traits through the use of dense markers covering the whole genome. For a successful application of GS, accuracy of the prediction of genomewide breeding value (GW-EBV) is a key issue to consider. Here we investigated the accuracy and possible bias of GW-EBV prediction, using real bovine SNP genotyping (18,991 SNPs) and phenotypic data of 500 Norwegian Red bulls. The study was performed on milk yield, fat yield, protein yield, first lactation mastitis traits, and calving ease. Three methods, best linear unbiased prediction (G-BLUP), Bayesian statistics (BayesB), and a mixture model approach (MIXTURE), were used to estimate marker effects, and their accuracy and bias were estimated by usin... Genetics journals http://www.medworm.com/rss/comments.php?id=3007033 Wed, 18 Nov 2009 16:39:31 +0100 3007033 http://www.medworm.com/index.php?rid=3007032&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F1105%3Frss%3D1 Inbreeding depression and mating systems evolution are closely linked, because the purging of deleterious mutations and the fitness of individuals may depend on outcrossing vs. selfing rates. Further, the accumulation of deleterious mutations may vary among genomic regions, especially for genes closely linked to loci under balancing selection. Sporophytic self-incompatibility (SSI) is a common genetic mechanism in angiosperm that enables hermaphrodite plants to avoid selfing and promote outcrossing. The SSI phenotype is determined by the S locus and may depend on dominance relationships among alleles. Since most individuals are heterozygous at the S locus and recombination is suppressed in the S-locus region, it has been suggested that deleterious mutations could accumulate at genes linked... Genetics journals http://www.medworm.com/rss/comments.php?id=3007032 Wed, 18 Nov 2009 16:39:31 +0100 3007032 http://www.medworm.com/index.php?rid=3007031&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F1087%3Frss%3D1 Sampling distributions play an important role in population genetics analyses, but closed-form sampling formulas are generally intractable to obtain. In the presence of recombination, there is no known closed-form sampling formula that holds for an arbitrary recombination rate. However, we recently showed that it is possible to obtain useful closed-form sampling formulas when the population-scaled recombination rate is large. Specifically, in the case of the two-locus infinite-alleles model, we considered an asymptotic expansion of the sampling formula in inverse powers of and obtained closed-form expressions for the first few terms in the expansion. In this article, we generalize this result to an arbitrary finite-alleles mutation model and show that, up to the first few terms in the expa... Genetics journals http://www.medworm.com/rss/comments.php?id=3007031 Wed, 18 Nov 2009 16:39:31 +0100 3007031 http://www.medworm.com/index.php?rid=3007030&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F1079%3Frss%3D1 Much recent work in the theoretical study of adaptation has focused on the so-called strong selection–weak mutation (SSWM) limit, wherein adaptation is due to new mutations of definite selective advantage. This work, in turn, has focused on the first step (substitution) during adaptive evolution. Here we extend this theory to allow multiple steps during adaptation. We find analytic solutions to the probability that adaptation follows a certain path during evolution as well as the probability that adaptation arrives at a given genotype regardless of the path taken. We also consider the probability of parallel adaptation and the proportion of the total increase in fitness caused by the first substitution. Our key assumption is that there is no epistasis among beneficial mutations. (Sou... Genetics journals http://www.medworm.com/rss/comments.php?id=3007030 Wed, 18 Nov 2009 16:39:31 +0100 3007030 http://www.medworm.com/index.php?rid=3007029&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F1065%3Frss%3D1 We have evaluated the extent to which SNPs identified by genomewide surveys as showing unusually high levels of population differentiation in humans have experienced recent positive selection, starting from a set of 32 nonsynonymous SNPs in 27 genes highlighted by the HapMap1 project. These SNPs were genotyped again in the HapMap samples and in the Human Genome Diversity Project–Centre d'Etude du Polymorphisme Humain (HGDP–CEPH) panel of 52 populations representing worldwide diversity; extended haplotype homozygosity was investigated around all of them, and full resequence data were examined for 9 genes (5 from public sources and 4 from new data sets). For 7 of the genes, genotyping errors were responsible for an artifactual signal of high population differentiation and for 2, ... Genetics journals http://www.medworm.com/rss/comments.php?id=3007029 Wed, 18 Nov 2009 16:39:31 +0100 3007029 http://www.medworm.com/index.php?rid=3007028&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F1055%3Frss%3D1 QST is a standardized measure of the genetic differentiation of a quantitative trait among populations. The distribution of QST's for neutral traits can be predicted from the FST for neutral marker loci. To test for the neutral differentiation of a quantitative trait among populations, it is necessary to ask whether the QST of that trait is in the tail of the probability distribution of neutral traits. This neutral distribution can be estimated using the Lewontin–Krakauer distribution and the FST from a relatively small number of marker loci. We develop a simulation method to test whether the QST of a given trait is consistent with the null hypothesis of selective neutrality over space. The method is most powerful with small mean FST, strong selection, and a large number (>10) of ... Genetics journals http://www.medworm.com/rss/comments.php?id=3007028 Wed, 18 Nov 2009 16:39:31 +0100 3007028 http://www.medworm.com/index.php?rid=3007027&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F1041%3Frss%3D1 The capacity for phenotypic evolution is dependent upon complex webs of functional interactions that connect genotype and phenotype. Wrinkly spreader (WS) genotypes arise repeatedly during the course of a model Pseudomonas adaptive radiation. Previous work showed that the evolution of WS variation was explained in part by spontaneous mutations in wspF, a component of the Wsp-signaling module, but also drew attention to the existence of unknown mutational causes. Here, we identify two new mutational pathways (Aws and Mws) that allow realization of the WS phenotype: in common with the Wsp module these pathways contain a di-guanylate cyclase-encoding gene subject to negative regulation. Together, mutations in the Wsp, Aws, and Mws regulatory modules account for the spectrum of WS phenotype-ge... Genetics journals http://www.medworm.com/rss/comments.php?id=3007027 Wed, 18 Nov 2009 16:39:31 +0100 3007027 http://www.medworm.com/index.php?rid=3007026&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F1027%3Frss%3D1 Ovarian follicle formation in Drosophila melanogaster requires stall (stl) gene function, both within and outside the ovary, for follicle individualization, stalk cell intercalation, and oocyte localization. We have identified the stl transcript as CG3622 and confirmed the presence of three alternatively spliced isoforms, contrary to current genome annotation. Here we show that the gene is expressed in both ovarian and brain tissues, which is consistent with previous evidence of an ovary nonautonomous function. On the basis of amino acid sequence, stl encodes a metalloprotease similar to the "a disintegrin and metalloprotease with thrombospondin" (ADAMTS) family. Although stl mutant ovaries fail to maintain the branched structure of the fusome and periodically show improperly localized ooc... Genetics journals http://www.medworm.com/rss/comments.php?id=3007026 Wed, 18 Nov 2009 16:39:31 +0100 3007026 http://www.medworm.com/index.php?rid=3007025&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F1005%3Frss%3D1 The Drosophila melanogaster wing is a model system for analyzing the genetic control of organ size, shape, and pattern formation. The formation of the wing involves a variety of processes, such as cell growth, proliferation, pattern formation, and differentiation. These developmental processes are under genetic control, and many genes participating in specific aspects of wing development have already being characterized. In this work, we aim to identify novel genes regulating wing growth and patterning. To this end, we have carried out a gain-of-function screen generating novel P-UAS (upstream activating sequences) insertions allowing forced gene expression. We produced 3340 novel P-UAS insertions and isolated 300 that cause a variety of wing phenotypes in combination with a Gal4 driver ex... Genetics journals http://www.medworm.com/rss/comments.php?id=3007025 Wed, 18 Nov 2009 16:39:31 +0100 3007025 http://www.medworm.com/index.php?rid=3007024&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F979%3Frss%3D1 Ethylene (C2H4) is a unique plant-signaling molecule that regulates numerous developmental processes. The key enzyme in the two-step biosynthetic pathway of ethylene is 1-aminocyclopropane-1-carboxylate synthase (ACS), which catalyzes the conversion of S-adenosylmethionine (AdoMet) to ACC, the precursor of ethylene. To understand the function of this important enzyme, we analyzed the entire family of nine ACS isoforms (ACS1, ACS2, ACS4-9, and ACS11) encoded in the Arabidopsis genome. Our analysis reveals that members of this protein family share an essential function, because individual ACS genes are not essential for Arabidopsis viability, whereas elimination of the entire gene family results in embryonic lethality. Phenotypic characterization of single and multiple mutants unmasks unique... Genetics journals http://www.medworm.com/rss/comments.php?id=3007024 Wed, 18 Nov 2009 16:39:30 +0100 3007024 http://www.medworm.com/index.php?rid=3007023&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F965%3Frss%3D1 PAR proteins (partitioning defective) are major regulators of cell polarity and asymmetric cell division. One of the par genes, par-1, encodes a Ser/Thr kinase that is conserved from yeast to mammals. In Caenorhabditis elegans, par-1 governs asymmetric cell division by ensuring the polar distribution of cell fate determinants. However the precise mechanisms by which PAR-1 regulates asymmetric cell division in C. elegans remain to be elucidated. We performed a genomewide RNAi screen and identified six genes that specifically suppress the embryonic lethal phenotype associated with mutations in par-1. One of these suppressors is mpk-1, the C. elegans homolog of the conserved mitogen activated protein (MAP) kinase ERK. Loss of function of mpk-1 restored embryonic viability, asynchronous cell d... Genetics journals http://www.medworm.com/rss/comments.php?id=3007023 Wed, 18 Nov 2009 16:39:30 +0100 3007023 http://www.medworm.com/index.php?rid=3007022&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F951%3Frss%3D1 The increasing evidence of fetal developmental effects on postnatal life, the still unknown fetal growth mechanisms impairing offspring generated by somatic nuclear transfer techniques, and the impact on stillbirth and dystocia in conventional reproduction have generated increasing attention toward mammalian fetal growth. We identified a highly significant quantitative trait locus (QTL) affecting fetal growth on bovine chromosome 6 in a specific resource population, which was set up by consistent use of embryo transfer and foster mothers and, thus, enabled dissection of fetal-specific genetic components of fetal growth. Merging our data with results from other cattle populations differing in historical and geographical origin and with comparative data from human whole-genome association ma... Genetics journals http://www.medworm.com/rss/comments.php?id=3007022 Wed, 18 Nov 2009 16:39:30 +0100 3007022 http://www.medworm.com/index.php?rid=3007021&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F941%3Frss%3D1 The polarization of post-mitotic neurons is poorly understood. Preexisting spatially asymmetric cues, distributed within the neuron or as extracellular gradients, could be required for neurons to polarize. Alternatively, neurons might have the intrinsic ability to polarize without any preestablished asymmetric cues. In Caenorhabditis elegans, the UNC-40 (DCC) receptor mediates responses to the extracellular UNC-6 (netrin) guidance cue. For the HSN neuron, an UNC-6 ventral-dorsal gradient asymmetrically localizes UNC-40 to the ventral HSN surface. There an axon forms, which is ventrally directed by UNC-6. In the absence of UNC-6, UNC-40 is equally distributed and the HSN axon travels anteriorly in response to other cues. However, we find that a single amino acid change in the UNC-40 ectodom... Genetics journals http://www.medworm.com/rss/comments.php?id=3007021 Wed, 18 Nov 2009 16:39:30 +0100 3007021 http://www.medworm.com/index.php?rid=3007020&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F929%3Frss%3D1 The [URE3] and [PSI+] prions are the infections amyloid forms of the Saccharomyces cerevisiae proteins Ure2p and Sup35p, respectively. Randomizing the order of the amino acids in the Ure2 and Sup35 prion domains while retaining amino acid composition does not block prion formation, indicating that amino acid composition, not primary sequence, is the predominant feature driving [URE3] and [PSI+] formation. Here we show that Ure2p promiscuously interacts with various compositionally similar proteins to influence [URE3] levels. Overexpression of scrambled Ure2p prion domains efficiently increases de novo formation of wild-type [URE3] in vivo. In vitro, amyloid aggregates of the scrambled prion domains efficiently seed wild-type Ure2p amyloid formation, suggesting that the wild-type and scramb... Genetics journals http://www.medworm.com/rss/comments.php?id=3007020 Wed, 18 Nov 2009 16:39:30 +0100 3007020 http://www.medworm.com/index.php?rid=3007019&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F917%3Frss%3D1 Vertebrate and invertebrate genomes contain scores of small secreted or transmembrane proteins with two immunoglobulin (Ig) domains. Many of them are expressed in the nervous system, yet their function is not well understood. We analyze here knockout alleles of all eight members of a family of small secreted or transmembrane Ig domain proteins, encoded by the Caenorhabditis elegans zig ("zwei Ig Domänen") genes. Most of these family members display the unusual feature of being coexpressed in a single neuron, PVT, whose axon is located along the ventral midline of C. elegans. One of these genes, zig-4, has previously been found to be required for maintaining axon position postembryonically in the ventral nerve cord of C. elegans. We show here that loss of zig-3 function results in simi... Genetics journals http://www.medworm.com/rss/comments.php?id=3007019 Wed, 18 Nov 2009 16:39:30 +0100 3007019 http://www.medworm.com/index.php?rid=3007018&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F905%3Frss%3D1 The meiotic prophase chromosome has a unique architecture. At the onset of leptotene, the replicated sister chromatids are organized along an axial element. During zygotene, as homologous chromosomes pair and synapse, a synaptonemal complex forms via the assembly of a transverse element between the two axial elements. However, due to the limitations of light and electron microscopy, little is known about chromatin organization with respect to the chromosome axes and about the spatial progression of synapsis in three dimensions. Three-dimensional structured illumination microscopy (3D-SIM) is a new method of superresolution optical microscopy that overcomes the 200-nm diffraction limit of conventional light microscopy and reaches a lateral resolution of at least 100 nm. Using 3D-SIM and ant... Genetics journals http://www.medworm.com/rss/comments.php?id=3007018 Wed, 18 Nov 2009 16:39:30 +0100 3007018 http://www.medworm.com/index.php?rid=3007017&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F897%3Frss%3D1 Epithelial polarity is established and maintained by competition between determinants that define the apical and basolateral domains. Cell–cell adhesion complexes, or adherens junctions, form at the interface of these regions. Mutations in adhesion components as well as apical determinants normally lead to an expansion of the basolateral domain. Here we investigate the genetic relationship between the polarity determinants and adhesion and show that the levels of the adhesion protein Armadillo affect competition. We find that in arm mutants, even a modest reduction in the basolateral component lgl leads to a full apical domain expansion or lgl phenotype. By using an allelic series of Armadillo mutations, we show that there is a threshold at which basolateral expansion can be reversed... Genetics journals http://www.medworm.com/rss/comments.php?id=3007017 Wed, 18 Nov 2009 16:39:30 +0100 3007017 http://www.medworm.com/index.php?rid=3007016&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F885%3Frss%3D1 The intraflagellar transport machinery is required for the assembly of cilia. It has been investigated by biochemical, genetic, and computational methods that have identified at least 21 proteins that assemble into two subcomplexes. It has been hypothesized that complex A is required for retrograde transport. Temperature-sensitive mutations in FLA15 and FLA17 show defects in retrograde intraflagellar transport (IFT) in Chlamydomonas. We show that IFT144 and IFT139, two complex A proteins, are encoded by FLA15 and FLA17, respectively. The fla15 allele is a missense mutation in a conserved cysteine and the fla17 allele is an in-frame deletion of three exons. The flagellar assembly defect of each mutant is rescued by the respective transgenes. In fla15 and fla17 mutants, bulges form in the di... Genetics journals http://www.medworm.com/rss/comments.php?id=3007016 Wed, 18 Nov 2009 16:39:30 +0100 3007016 http://www.medworm.com/index.php?rid=3007015&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F873%3Frss%3D1 We describe a fifth yeast CorA homolog (Mnr2) required for Mg homeostasis. MNR2 gene inactivation was associated with an increase in both the Mg requirement and the Mg content of yeast cells. In Mg-replete conditions, wild-type cells accumulated an intracellular store of Mg that supported growth under deficient conditions. An mnr2 mutant was unable to access this store, suggesting that Mg was trapped in an intracellular compartment. Mnr2 was localized to the vacuole membrane, implicating this organelle in Mg storage. The mnr2 mutant growth and Mg-content phenotypes were dependent on vacuolar proton-ATPase activity, but were unaffected by the loss of mitochondrial Mg uptake, indicating a specific dependence on vacuole function. Overexpression of Mnr2 suppressed the growth defect of an alr1 ... Genetics journals http://www.medworm.com/rss/comments.php?id=3007015 Wed, 18 Nov 2009 16:39:30 +0100 3007015 http://www.medworm.com/index.php?rid=3007014&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F861%3Frss%3D1 Maintenance and expression of mitochondrial DNA (mtDNA) are essential for the cell and the organism. In humans, several mutations in the adenine nucleotide translocase gene ANT1 are associated with multiple mtDNA deletions and autosomal dominant forms of progressive external ophthalmoplegia (adPEO). The mechanisms underlying the mtDNA instability are still obscure. A current hypothesis proposes that these pathogenic mutations primarily uncouple the mitochondrial inner membrane, which secondarily causes mtDNA instability. Here we show that the three adPEO-associated mutations equivalent to A114P, L98P, and V289M introduced into the Podospora anserina ANT1 ortholog dominantly cause severe growth defects, decreased reactive oxygen species production (ROS), decreased mitochondrial inner membra... Genetics journals http://www.medworm.com/rss/comments.php?id=3007014 Wed, 18 Nov 2009 16:39:30 +0100 3007014 http://www.medworm.com/index.php?rid=3007013&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F853%3Frss%3D1 This study demonstrates the feasibility of in planta functional analysis of wheat proteins and that the Tryptophan-rich region is the most important region of both PINA and PINB. (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=3007013 Wed, 18 Nov 2009 16:39:30 +0100 3007013 http://www.medworm.com/index.php?rid=3007012&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F831%3Frss%3D1 The large nucleus limited noncoding hsr-n RNA of Drosophila melanogaster is known to associate with a variety of heterogeneous nuclear RNA-binding proteins (hnRNPs) and certain other RNA-binding proteins to assemble the nucleoplasmic omega speckles. In this article, we show that RNAi-mediated depletion of this noncoding RNA dominantly suppresses apoptosis, in eye and other imaginal discs, triggered by induced expression of Rpr, Grim, or caspases (initiator as well as effector), all of which are key regulators/effectors of the canonical caspase-mediated cell death pathway. We also show, for the first time, a genetic interaction between the noncoding hsr transcripts and the c-Jun N-terminal kinase (JNK) signaling pathway since downregulation of hsr transcripts suppressed JNK activation. In a... Genetics journals http://www.medworm.com/rss/comments.php?id=3007012 Wed, 18 Nov 2009 16:39:30 +0100 3007012 http://www.medworm.com/index.php?rid=3007011&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F821%3Frss%3D1 Oxygen is critically important to metazoan life, and the EGL-9/PHD enzymes are key regulators of hypoxia (low oxygen) response. When oxygen levels are high, the EGL-9/PHD proteins hydroxylate hypoxia-inducible factor (HIF) transcription factors. Once hydroxylated, HIF subunits bind to von Hippel-Lindau (VHL) E3 ligases and are degraded. Prior genetic analyses in Caenorhabditis elegans had shown that EGL-9 also acted through a vhl-1-independent pathway to inhibit HIF-1 transcriptional activity. Here, we characterize this novel EGL-9 function. We employ an array of complementary methods to inhibit EGL-9 hydroxylase activity in vivo. These include hypoxia, hydroxylase inhibitors, mutation of the proline in HIF-1 that is normally modified by EGL-9, and mutation of the EGL-9 catalytic core. Rem... Genetics journals http://www.medworm.com/rss/comments.php?id=3007011 Wed, 18 Nov 2009 16:39:30 +0100 3007011 http://www.medworm.com/index.php?rid=3007010&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F811%3Frss%3D1 Drosophila melanogaster males have a well-characterized regulatory system that increases X-linked gene expression. This essential process restores the balance between X-linked and autosomal gene products in males. A complex composed of the male-specific lethal (MSL) proteins and RNA is recruited to the body of transcribed X-linked genes where it modifies chromatin to increase expression. The RNA components of this complex, roX1 and roX2 (RNA on the X1, RNA on the X2), are functionally redundant. Males mutated for both roX genes have dramatically reduced survival. We show that reversal of sex chromosome inheritance suppresses lethality in roX1 roX2 males. Genetic tests indicate that the effect on male survival depends upon the presence and source of the Y chromosome, revealing a germ line i... Genetics journals http://www.medworm.com/rss/comments.php?id=3007010 Wed, 18 Nov 2009 16:39:30 +0100 3007010 http://www.medworm.com/index.php?rid=3007009&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F793%3Frss%3D1 Telomere binding proteins protect chromosome ends from degradation and mask chromosome termini from checkpoint surveillance. In Saccharomyces cerevisiae, Cdc13 binds single-stranded G-rich telomere repeats, maintaining telomere integrity and length. Two additional proteins, Ten1 and Stn1, interact with Cdc13 but their contributions to telomere integrity are not well defined. Ten1 is known to prevent accumulation of aberrant single-stranded telomere DNA; whether this results from defective end protection or defective telomere replication is unclear. Here we report our analysis of a new group of ten1 temperature-sensitive (ts) mutants. At permissive temperatures, ten1-ts strains display greatly elongated telomeres. After shift to nonpermissive conditions, however, ten1-ts mutants accumulate ... Genetics journals http://www.medworm.com/rss/comments.php?id=3007009 Wed, 18 Nov 2009 16:39:30 +0100 3007009 http://www.medworm.com/index.php?rid=3007008&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F779%3Frss%3D1 Pif1, an evolutionarily conserved helicase, negatively regulates telomere length by removing telomerase from chromosome ends. Pif1 has also been implicated in DNA replication processes such as Okazaki fragment maturation and replication fork pausing. We find that overexpression of Saccharomyces cervisiae PIF1 results in dose-dependent growth inhibition. Strong overexpression causes relocalization of the DNA damage response factors Rfa1 and Mre11 into nuclear foci and activation of the Rad53 DNA damage checkpoint kinase, indicating that the toxicity is caused by accumulation of DNA damage. We screened the complete set of ~4800 haploid gene deletion mutants and found that moderate overexpression of PIF1, which is only mildly toxic on its own, causes growth defects in strains with mutations i... Genetics journals http://www.medworm.com/rss/comments.php?id=3007008 Wed, 18 Nov 2009 16:39:30 +0100 3007008 http://www.medworm.com/index.php?rid=3007007&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F773%3Frss%3D1 There is no doubt about the magnitude of Charles Darwin's contributions to science. There has, however, been a long-running debate about how brilliant he was. His kind of intelligence was clearly different from that of the great physicists who are deemed geniuses. Here, the nature of Darwin's intelligence is examined in the light of Darwin's actual style of working. Surprisingly, the world of literature and the field of neurobiology might supply more clues to resolving the puzzle than conventional scientific history. Those clues suggest that the apparent discrepancy between Darwin's achievements and his seemingly pedestrian way of thinking reveals nothing to Darwin's discredit but rather a too narrow and inappropriate set of criteria for "genius." The implications of Darwin's particular cr... Genetics journals http://www.medworm.com/rss/comments.php?id=3007007 Wed, 18 Nov 2009 16:39:30 +0100 3007007 http://www.medworm.com/index.php?rid=3007006&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F767%3Frss%3D1 Most scientific theories, even revolutionary ones, change the practice of a particular science but have few consequences for culture or society at large. But Darwinism, it has often been said, is different in this respect. Since the publication of The Origin of Species, many have claimed that Darwinism has a number of profound social implications. Here, I briefly consider three of these: the economic, the political, and the religious. I suggest that, for the most part, these supposed implications have been misconstrued or exaggerated. Indeed, it is reasonably clear that the chain of implication sometimes primarily ran in the opposite direction—from, for instance, economics and political theory to Darwinism. (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=3007006 Wed, 18 Nov 2009 16:39:30 +0100 3007006 http://www.medworm.com/index.php?rid=3007005&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2F757%3Frss%3D1 Darwin's theory of natural selection lacked an adequate account of inheritance, making it logically incomplete. We review the interaction between evolution and genetics, showing how, unlike Mendel, Darwin's lack of a model of the mechanism of inheritance left him unable to interpret his own data that showed Mendelian ratios, even though he shared with Mendel a more mathematical and probabilistic outlook than most biologists of his time. Darwin's own "pangenesis" model provided a mechanism for generating ample variability on which selection could act. It involved, however, the inheritance of characters acquired during an organism's life, which Darwin himself knew could not explain some evolutionary situations. Once the particulate basis of genetics was understood, it was seen to allow varia... Genetics journals http://www.medworm.com/rss/comments.php?id=3007005 Wed, 18 Nov 2009 16:39:30 +0100 3007005 http://www.medworm.com/index.php?rid=3007004&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2Fix%3Frss%3D1 (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=3007004 Wed, 18 Nov 2009 16:39:30 +0100 3007004 http://www.medworm.com/index.php?rid=3007003&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F3%2FNP%3Frss%3D1 (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=3007003 Wed, 18 Nov 2009 16:39:30 +0100 3007003 http://www.medworm.com/index.php?rid=2937805&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F2%2F756%3Frss%3D1 (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=2937805 Wed, 28 Oct 2009 18:33:17 +0100 2937805 http://www.medworm.com/index.php?rid=2937804&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F2%2F755-a%3Frss%3D1 (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=2937804 Wed, 28 Oct 2009 18:33:17 +0100 2937804 http://www.medworm.com/index.php?rid=2937803&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F2%2F755%3Frss%3D1 (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=2937803 Wed, 28 Oct 2009 18:33:17 +0100 2937803 http://www.medworm.com/index.php?rid=2937802&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F2%2F751%3Frss%3D1 Variation of gene length imposes a challenge on genes requiring coexpression. Using a large human protein complex data set, we show that genes encoding subunits of the same protein complex tend to have similar length. The length uniformity is greater for complexes with stronger coexpression. We also show that the rate of gene length evolution is associated with gene coexpression level within a complex. These results suggest a new angle in understanding the evolution of protein complexes as well as the regulation of gene coexpression. (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=2937802 Wed, 28 Oct 2009 18:33:16 +0100 2937802 http://www.medworm.com/index.php?rid=2937801&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F2%2F747%3Frss%3D1 The point mutation rate of phage X174 was determined using the fluctuation test. After identifying the genetic changes associated with the selected phenotype, we obtained an estimate of 1.0 x 10–6 substitutions per base per round of copying, which is consistent with Drake's rule (0.003 mutations per genome per round of copying in DNA-based microorganisms). (Source: Genetics) Genetics journals http://www.medworm.com/rss/comments.php?id=2937801 Wed, 28 Oct 2009 18:33:16 +0100 2937801 http://www.medworm.com/index.php?rid=2937800&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F2%2F733%3Frss%3D1 Identification of risk alleles for human behavioral disorders through genomewide association studies (GWAS) has been hampered by a daunting multiple testing problem. This problem can be circumvented for some phenotypes by combining genomewide studies in model organisms with subsequent candidate gene association analyses in human populations. Here, we characterized genetic networks that underlie the response to ethanol exposure in Drosophila melanogaster by measuring ethanol knockdown time in 40 wild-derived inbred Drosophila lines. We associated phenotypic variation in ethanol responses with genomewide variation in gene expression and identified modules of correlated transcripts associated with a first and second exposure to ethanol vapors as well as the induction of tolerance. We validate... Genetics journals http://www.medworm.com/rss/comments.php?id=2937800 Wed, 28 Oct 2009 18:33:16 +0100 2937800 http://www.medworm.com/index.php?rid=2937799&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F2%2F723%3Frss%3D1 Flowering time, a critical adaptive trait, is modulated by several environmental cues. These external signals converge on a small set of genes that in turn mediate the flowering response. Mutant analysis and subsequent molecular studies have revealed that one of these integrator genes, FLOWERING LOCUS T (FT), responds to photoperiod and temperature cues, two environmental parameters that greatly influence flowering time. As the central player in the transition to flowering, the protein coding sequence of FT and its function are highly conserved across species. Using QTL mapping with a new advanced intercross-recombinant inbred line (AI-RIL) population, we show that a QTL tightly linked to FT contributes to natural variation in the flowering response to the combined effects of photoperiod a... Genetics journals http://www.medworm.com/rss/comments.php?id=2937799 Wed, 28 Oct 2009 18:33:16 +0100 2937799 http://www.medworm.com/index.php?rid=2937798&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F2%2F709%3Frss%3D1 We assume that quantitative measurements on a considered trait and unphased genotype data at certain marker loci are available on a sample of individuals from a background population. Our goal is to map quantitative trait loci by using a Bayesian model that performs, and makes use of, probabilistic reconstructions of the recent unobserved genealogical history (a pedigree and a gene flow at the marker loci) of the sampled individuals. This work extends variance component-based linkage analysis to settings where the unobserved pedigrees are considered as latent variables. In addition to the measured trait values and unphased genotype data at the marker loci, the method requires as an input estimates of the population allele frequencies and of a marker map, as well as some parameters related ... Genetics journals http://www.medworm.com/rss/comments.php?id=2937798 Wed, 28 Oct 2009 18:33:16 +0100 2937798 http://www.medworm.com/index.php?rid=2937797&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F2%2F693%3Frss%3D1 Ovarioles are the functional unit of the female insect reproductive organs and the number of ovarioles per ovary strongly influences egg-laying rate and fecundity. Social evolution in the honeybee (Apis mellifera) has resulted in queens with 200–360 total ovarioles and workers with usually 20 or less. In addition, variation in ovariole number among workers relates to worker sensory tuning, foraging behavior, and the ability to lay unfertilized male-destined eggs. To study the genetic architecture of worker ovariole number, we performed a series of crosses between Africanized and European bees that differ in worker ovariole number. Unexpectedly, these crosses produced transgressive worker phenotypes with extreme ovariole numbers that were sensitive to the social environment. We used a... Genetics journals http://www.medworm.com/rss/comments.php?id=2937797 Wed, 28 Oct 2009 18:33:16 +0100 2937797 http://www.medworm.com/index.php?rid=2937796&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F2%2F685%3Frss%3D1 The genetic variation present in a species depends on the interplay between mutation, population size, and natural selection. At mutation-(purifying) selection balance (MSB) in a large population, the standing genetic variance for a trait (VG) is predicted to be proportional to the mutational variance for the trait (VM); VM is proportional to the mutation rate for the trait. The ratio VM/VG predicts the average strength of selection (S) against a new mutation. Here we compare VM and VG for lifetime reproductive success ( fitness) and body volume in two species of self-fertilizing rhabditid nematodes, Caenorhabditis briggsae and C. elegans, which the evidence suggests have different mutation rates. Averaged over traits, species, and populations within species, the relationship between VG an... Genetics journals http://www.medworm.com/rss/comments.php?id=2937796 Wed, 28 Oct 2009 18:33:16 +0100 2937796 http://www.medworm.com/index.php?rid=2937795&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F2%2F673%3Frss%3D1 Mutation and recombination are the two main forces generating genetic variation. Most of this variation may be deleterious. Because recombination can reorganize entire genes and genetic circuits, it may have much greater consequences than point mutations. We here explore the effects of recombination on models of transcriptional regulation circuits that play important roles in embryonic development. We show that recombination has weaker deleterious effects on the expression phenotypes of these circuits than mutations. In addition, if a population of such circuits evolves under the influence of mutation and recombination, we find that three key properties emerge: (1) deleterious effects of mutations are reduced dramatically; (2) the diversity of genotypes in the population is greatly increas... Genetics journals http://www.medworm.com/rss/comments.php?id=2937795 Wed, 28 Oct 2009 18:33:16 +0100 2937795 http://www.medworm.com/index.php?rid=2937794&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F2%2F663%3Frss%3D1 Pentatricopeptide repeat (PPR) proteins compose a family of nuclear-encoded transcriptional regulators of cytoplasmic genes. They have shown dramatic expansion in copy number in plants, and although the functional importance of many remains unclear, a subset has been repeatedly implicated as nuclear restorers for cytoplasmic male sterility. Here we investigate the molecular population genetics and molecular evolution of seven single-copy PPR genes in the outcrossing model plant Arabidopsis lyrata. In comparison with neutral reference loci, we find, on average, elevated levels of polymorphism and an excess of high-frequency variants at these PPR genes, suggesting that natural selection is maintaining polymorphism at some of these loci. This elevation in diversity persists when we control fo... Genetics journals http://www.medworm.com/rss/comments.php?id=2937794 Wed, 28 Oct 2009 18:33:16 +0100 2937794 http://www.medworm.com/index.php?rid=2937793&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F2%2F651%3Frss%3D1 Codon usage bias is the nonrandom use of synonymous codons for the same amino acid. Most population genetic models of codon usage evolution assume that the population is at mutation–selection–drift equilibrium. Natural populations, however, frequently deviate from equilibrium, often because of recent demographic changes. Here, we construct a matrix model that includes the effects of a recent change in population size on estimates of selection on preferred vs. unpreferred codons. Our results suggest that patterns of synonymous polymorphisms affecting codon usage can be quite erratic after such a change; statistical methods that fail to take demographic effects into account can then give incorrect estimates of important parameters. We propose a new method that can accurately esti... Genetics journals http://www.medworm.com/rss/comments.php?id=2937793 Wed, 28 Oct 2009 18:33:16 +0100 2937793 http://www.medworm.com/index.php?rid=2937792&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F2%2F639%3Frss%3D1 We present a model in which the genotype is presented as a set folding free energies of cell proteins. Mutations occur upon replication, so stabilities of some proteins in daughter cells differ from those in the parent cell by amounts deduced from the distribution of mutational effects on protein stability. The genotype–phenotype relationship posits that the cell's fitness (replication rate) is proportional to the concentration of its folded proteins and that unstable essential proteins result in lethality. Simulations reveal that lethal mutagenesis occurs at a mutation rate close to seven mutations in each replication of the genome for RNA viruses and at about half that rate for DNA-based organisms, in accord with earlier predictions from analytical theory and experimental results. ... Genetics journals http://www.medworm.com/rss/comments.php?id=2937792 Wed, 28 Oct 2009 18:33:16 +0100 2937792 http://www.medworm.com/index.php?rid=2937791&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F2%2F629%3Frss%3D1 Fluctuations in age structure caused by environmental stochasticity create autocorrelation and transient fluctuations in both population size and allele frequency, which complicate demographic and evolutionary analyses. Following a suggestion of Fisher, we show that weighting individuals of different age by their reproductive value serves as a filter, removing temporal autocorrelation in population demography and evolution due to stochastic age structure. Assuming weak selection, random mating, and a stationary distribution of environments with no autocorrelation, we derive a diffusion approximation for evolution of the reproductive value weighted allele frequency. The expected evolution obeys an adaptive topography defined by the long-run growth rate of the population. The expected fitnes... Genetics journals http://www.medworm.com/rss/comments.php?id=2937791 Wed, 28 Oct 2009 18:33:16 +0100 2937791 http://www.medworm.com/index.php?rid=2937790&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F2%2F619%3Frss%3D1 In this study, we used the Bombyx mori mutant scaleless (sl), which displays a nearly complete loss of wing scales, to explore the mechanism of lepidopteran wing-scale formation. We found that Bm-ASH2, one of four Bombyx achaete-scute homologs, is highly expressed in early pupal wings of wild-type silkworms, but its expression is severely reduced in sl pupal wings. Through molecular characterization of the mutant locus using luciferase and gel shift assays, genetic analysis of recombining populations, and in vivo rescue experiments, we provide evidence that a 26-bp deletion within the Bm-ASH2 promoter is closely linked to the sl locus and leads to loss of Bm-ASH2 expression and the scaleless-wings phenotype. Thus, the Bm-ASH2 appears to play a critical role in scale formation in B. mori. T... Genetics journals http://www.medworm.com/rss/comments.php?id=2937790 Wed, 28 Oct 2009 18:33:15 +0100 2937790 http://www.medworm.com/index.php?rid=2937789&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F2%2F607%3Frss%3D1 Selective protein degradation is a key regulator of neuronal development and synaptogenesis. Complexes that target proteins for degradation often contain F-box proteins. Here we characterize MEC-15, an F-box protein with WD repeats, which is required for the development and function of Caenorhabditis elegans touch receptor neurons (TRNs). Mutations in mec-15 produce defects in TRN touch sensitivity, chemical synapse formation, and cell-body morphology. All mec-15 mutant phenotypes are enhanced by mutations in a MAP kinase pathway composed of the MAPKKK DLK-1, the MAPKK MKK-4, and the p38 MAPK PMK-3. A mutation of the rpm-1 gene, which encodes an E3 ubiquitin ligase that negatively regulates this pathway to promote synaptogenesis, suppresses only the mec-15 cell-body defect. Thus, MEC-15 ac... Genetics journals http://www.medworm.com/rss/comments.php?id=2937789 Wed, 28 Oct 2009 18:33:15 +0100 2937789 http://www.medworm.com/index.php?rid=2937788&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F2%2F595%3Frss%3D1 Studying the development and mechanisms of sensory perception is challenging in organisms with complex neuronal networks. The worm Caenorhabditis elegans possesses a simple neuronal network of 302 neurons that includes 60 ciliated sensory neurons (CSNs) for detecting external sensory input. C. elegans is thus an excellent model in which to study sensory neuron development, function, and behavior. We have generated a genetic rescue system that allows in vivo analyses of isolated CSNs at both cellular and systemic levels. We used the RFX transcription factor DAF-19, a key regulator of ciliogenesis. Mutations in daf-19 result in the complete absence of all sensory cilia and thus of external sensory input. In daf-19 mutants, we used cell-specific rescue of DAF-19 function in selected neurons, ... Genetics journals http://www.medworm.com/rss/comments.php?id=2937788 Wed, 28 Oct 2009 18:33:15 +0100 2937788 http://www.medworm.com/index.php?rid=2937787&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F2%2F581%3Frss%3D1 The microphthalmia-associated transcription factor (Mitf) has emerged as an important model for gene regulation in eukaryotic organisms. In vertebrates, it regulates the development of several cell types including melanocytes and has also been shown to play an important role in melanoma. In vitro, the activity of MITF is regulated by multiple signaling pathways, including the KITL/KIT/B-Raf pathway, which results in phosphorylation of MITF on serine residues 73 and 409. However, the precise role of signaling to MITF in vivo remains largely unknown. Here, we use a BAC transgene rescue approach to introduce specific mutations in MITF to study the importance of specific phospho-acceptor sites and protein domains. We show that mice that carry a BAC transgene where single-amino-acid substitutio... Genetics journals http://www.medworm.com/rss/comments.php?id=2937787 Wed, 28 Oct 2009 18:33:15 +0100 2937787 http://www.medworm.com/index.php?rid=2937786&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F2%2F563%3Frss%3D1 We examined 3 existing and 12 newly generated mutations in the Drosophila type I receptor gene, saxophone (sax), the ortholog of the human Activin Receptor-Like Kinase1 and -2 (ALK1/ACVRL1 and ALK2/ACVR1) genes. Our genetic analyses identified two distinct classes of sax alleles. The first class consists of homozygous viable gain-of-function (GOF) alleles that exhibit (1) synthetic lethality in combination with mutations in BMP pathway components, and (2) significant maternal effect lethality that can be rescued by an increased dosage of the BMP encoding gene, dpp+. In contrast, the second class consists of alleles that are recessive lethal and do not exhibit lethality in combination with mutations in other BMP pathway components. The alleles in this second class are clearly loss-of-functi... Genetics journals http://www.medworm.com/rss/comments.php?id=2937786 Wed, 28 Oct 2009 18:33:15 +0100 2937786 http://www.medworm.com/index.php?rid=2937785&cid=s_33050_50_f&fid=33050&url=http%3A%2F%2Fwww.genetics.org%2Fcgi%2Fcontent%2Fshort%2F183%2F2%2F547%3Frss%3D1 Species-specific regulation of gene expression contributes to the development and maintenance of reproductive isolation and to species differences in ecologically important traits. A better understanding of the evolutionary forces that shape regulatory variation and divergence can be developed by comparing expression differences among species and interspecific hybrids. Once expression differences are identified, the underlying genetics of regulatory variation or divergence can be explored. With the goal of associating cis and/or trans components of regulatory divergence with differences in gene expression, overall and allele-specific expression levels were assayed genomewide in female adult heads of Drosophila melanogaster, D. simulans, and their F1 hybrids. A greater proportion of cis dif... Genetics journals http://www.medworm.com/rss/comments.php?id=2937785 Wed, 28 Oct 2009 18:33:15 +0100 2937785