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Magwire M.M.,University of Cambridge | Fabian D.K.,University of Cambridge | Fabian D.K.,Institute of Population Genetics | Schweyen H.,University of Cambridge | And 4 more authors.
PLoS Genetics | Year: 2012

Variation in susceptibility to infectious disease often has a substantial genetic component in animal and plant populations. We have used genome-wide association studies (GWAS) in Drosophila melanogaster to identify the genetic basis of variation in susceptibility to viral infection. We found that there is substantially more genetic variation in susceptibility to two viruses that naturally infect D. melanogaster (DCV and DMelSV) than to two viruses isolated from other insects (FHV and DAffSV). Furthermore, this increased variation is caused by a small number of common polymorphisms that have a major effect on resistance and can individually explain up to 47% of the heritability in disease susceptibility. For two of these polymorphisms, it has previously been shown that they have been driven to a high frequency by natural selection. An advantage of GWAS in Drosophila is that the results can be confirmed experimentally. We verified that a gene called pastrel-which was previously not known to have an antiviral function-is associated with DCV-resistance by knocking down its expression by RNAi. Our data suggest that selection for resistance to infectious disease can increase genetic variation by increasing the frequency of major-effect alleles, and this has resulted in a simple genetic basis to variation in virus resistance. © 2012 Magwire et al. Source

Kosiol C.,Institute of Population Genetics | Anisimova M.,ETH Zurich | Anisimova M.,Swiss Institute of Bioinformatics
Methods in Molecular Biology | Year: 2012

Populations evolve as mutations arise in individual organisms and, through hereditary transmission, may become "fixed" (shared by all individuals) in the population. Most mutations are lethal or have negative fitness consequences for the organism. Others have essentially no effect on organismal fitness and can become fixed through the neutral stochastic process known as random drift. However, mutations may also produce a selective advantage that boosts their chances of reaching fixation. Regions of genes where new mutations are beneficial, rather than neutral or deleterious, tend to evolve more rapidly due to positive selection. Genes involved in immunity and defense are a well-known example; rapid evolution in these genes presumably occurs because new mutations help organisms to prevail in evolutionary "arms races" with pathogens. In recent years, genome-wide scans for selection have enlarged our understanding of the evolution of the protein-coding regions of the various species. In this chapter, we focus on the methods to detect selection in protein-coding genes. In particular, we discuss probabilistic models and how they have changed with the advent of new genome-wide data now available. © 2012 Springer Science+Business Media, LLC. Source

Heyn P.,University of Edinburgh | Kalinka A.T.,Institute of Population Genetics | Tomancak P.,Max Planck Institute of Molecular Cell Biology and Genetics | Neugebauer K.M.,Yale University
BioEssays | Year: 2015

A gene's "expression profile" denotes the number of transcripts present relative to all other transcripts. The overall rate of transcript production is determined by transcription and RNA processing rates. While the speed of elongating RNA polymerase II has been characterized for many different genes and organisms, gene-architectural features - primarily the number and length of exons and introns - have recently emerged as important regulatory players. Several new studies indicate that rapidly cycling cells constrain gene-architecture toward short genes with a few introns, allowing efficient expression during short cell cycles. In contrast, longer genes with long introns exhibit delayed expression, which can serve as timing mechanisms for patterning processes. These findings indicate that cell cycle constraints drive the evolution of gene-architecture and shape the transcriptome of a given cell type. Furthermore, a tendency for short genes to be evolutionarily young hints at links between cellular constraints and the evolution of animal ontogeny. © 2015 The Authors. Source

Farlow A.,Gregor Mendel Institute of Molecular Plant Biology | Farlow A.,Institute of Population Genetics | Arnoux S.,Gregor Mendel Institute of Molecular Plant Biology | Doak T.G.,Indiana University Bloomington | Nordborg M.,Gregor Mendel Institute of Molecular Plant Biology
Genetics | Year: 2015

The rate at which new mutations arise in the genome is a key factor in the evolution and adaptation of species. Here we describe the rate and spectrum of spontaneous mutations for the fission yeast Schizosaccharomyces pombe, a key model organism with many similarities to higher eukaryotes. We undertook an  1700-generation mutation accumulation (MA) experiment with a haploid S. pombe, generating 422 single-base substitutions and 119 insertion-deletion mutations (indels) across the 96 replicates. This equates to a base-substitution mutation rate of 2.00 3 10210 mutations per site per generation, similar to that reported for the distantly related budding yeast Saccharomyces cerevisiae. However, these two yeast species differ dramatically in their spectrum of base substitutions, the types of indels (S. pombe is more prone to insertions), and the pattern of selection required to counteract a strong AT-biased mutation rate. Overall, our results indicate that GC-biased gene conversion does not play a major role in shaping the nucleotide composition of the S. pombe genome and suggest that the mechanisms of DNA maintenance may have diverged significantly between fission and budding yeasts. Unexpectedly, CpG sites appear to be excessively liable to mutation in both species despite the likely absence of DNA methylation. © 2015 by the Genetics Society of America. Source

Hansen M.,Sanford Burnham Institute for Medical Research | Flatt T.,Institute of Population Genetics | Flatt T.,Institute for Advanced Study | Flatt T.,University of Lausanne | Aguilaniu H.,Ecole Normale Superieure de Lyon
Cell Metabolism | Year: 2013

Reduced reproduction is associated with increased fat storage and prolonged life span in multiple organisms, but the underlying regulatory mechanisms remain poorly understood. Recent studies in several species provide evidence that reproduction, fat metabolism, and longevity are directly coupled. For instance, germline removal in the nematode Caenorhabditis elegans promotes longevity in part by modulating lipid metabolism through effects on fatty acid desaturation, lipolysis, and autophagy. Here, we review these recent studies and discuss the mechanisms by which reproduction modulates fat metabolism and life span. Elucidating the relationship between these processes could contribute to our understanding of age-related diseases including metabolic disorders. © 2013 Elsevier Inc. Source

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