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The independent domestication of local wild boar populations in Asia and Europe about 10,000 years ago led to distinct European and Asian pig breeds, each with very different phenotypic characteristics. During the Industrial Revolution, Chinese breeds were imported to Europe to improve commercial traits in European breeds. Here we demonstrate the presence of introgressed Asian haplotypes in European domestic pigs and selection signatures on some loci in these regions, using whole genome sequence data. The introgression signatures are widespread and the Asian haplotypes are rarely fixed. The Asian introgressed haplotypes are associated with regions harbouring genes involved in meat quality, development and fertility. We identify Asian-derived non-synonymous mutations in the AHR gene that associate with increased litter size in multiple European commercial lines. These findings demonstrate that increased fertility was an important breeding goal for early nineteenth century pig farmers, and that Asian variants of genes related to this trait were preferentially selected during the development of modern European pig breeds. Domestication of wild boar populations has led to phenotypically distinct European and Asian pig breeds. Here, the authors show that Asian haplotypes that have introgressed into European pig breeds harbour genes that control economically important traits such as meat quality, development and fertility.

Population-specific, positive selection promotes the diversity of populations and drives local adaptations in the population. However, little is known about population-specific, recent positive selection in the populations of cultivated cucumber (Cucumis sativus L.). Based on a genomic variation map of individuals worldwide, we implemented a Fisher’s combination method by combining 4 haplotype-based approaches: integrated haplotype score (iHS), number of segregating sites by length (nSL), cross-population extended haplotype homozygosity (XP-EHH), and Rsb. Overall, we detected 331, 2,147, and 3,772 population-specific, recent positive selective sites in the East Asian, Eurasian, and Xishuangbanna populations, respectively. Moreover, we found that these sites were related to processes for reproduction, response to abiotic and biotic stress, and regulation of developmental processes, indicating adaptations to their microenvironments. Meanwhile, the selective genes associated with traits of fruits were also observed, such as the gene related to the shorter fruit length in the Eurasian population and the gene controlling flesh thickness in the Xishuangbanna population. In addition, we noticed that soft sweeps were common in the East Asian and Xishuangbanna populations. Genes involved in hard or soft sweeps were related to developmental regulation and abiotic and biotic stress resistance. Our study offers a comprehensive candidate dataset of population-specific, selective signatures in cultivated cucumber populations. Our methods provide guidance for the analysis of population-specific, positive selection. These findings will help explore the biological mechanisms of adaptation and domestication of cucumber.

Evolutionary changes in enhancers are widely associated with variation in human traits and diseases. However, studies comprehensively quantifying levels of selection on enhancers at multiple evolutionary periods during recent human evolution and how enhancer evolution varies across human tissues are lacking. To address these questions, we integrated a dataset of 41,561 transcribed enhancers active in 41 different human tissues (FANTOM Consortium) with whole genome sequences of 1,668 individuals from the African, Asian, and European populations (1000 Genomes Project). Our analyses based on four different metrics (Tajima’s D, FST, H12, nSL) showed that ∼5.90% of enhancers showed evidence of recent positive selection and that genes associated with enhancers under very recent positive selection are enriched for diverse immune-related functions. The distributions of these metrics for brain and testis enhancers were often statistically significantly different and in the direction suggestive of less positive selection compared to those of other tissues; the same was true for brain and testis enhancers that are tissue-specific compared to those that are tissue-broad and for testis enhancers associated with tissue-enriched and non-tissue-enriched genes. These differences varied considerably across metrics and tissues and were generally in the form of changes in distributions’ shapes rather than shifts in their values. Collectively, these results suggest that many human enhancers experienced recent positive selection throughout multiple time periods in human evolutionary history, that this selection occurred in a tissue-dependent and immune-related functional context, and that much like the evolution of their protein-coding gene counterparts, the evolution of brain and testis enhancers has been markedly different from that of enhancers in other tissues.

Artificial selection has caused rapid evolution in domesticated species. The identification of selection footprints across domesticated genomes can contribute to uncover the genetic basis of phenotypic diversity. Genome wide footprints of pig domestication and selection were identified using massive parallel sequencing of pooled reduced representation libraries (RRL) representing ∼2% of the genome from wild boar and four domestic pig breeds (Large White, Landrace, Duroc and Pietrain) which have been under strong selection for muscle development, growth, behavior and coat color. Using specifically developed statistical methods that account for DNA pooling, low mean sequencing depth, and sequencing errors, we provide genome-wide estimates of nucleotide diversity and genetic differentiation in pig. Widespread signals suggestive of positive and balancing selection were found and the strongest signals were observed in Pietrain, one of the breeds most intensively selected for muscle development. Most signals were population-specific but affected genomic regions which harbored genes for common biological categories including coat color, brain development, muscle development, growth, metabolism, olfaction and immunity. Genetic differentiation in regions harboring genes related to muscle development and growth was higher between breeds than between a given breed and the wild boar. These results, suggest that although domesticated breeds have experienced similar selective pressures, selection has acted upon different genes. This might reflect the multiple domestication events of European breeds or could be the result of subsequent introgression of Asian alleles. Overall, it was estimated that approximately 7% of the porcine genome has been affected by selection events. This study illustrates that the massive parallel sequencing of genomic pools is a cost-effective approach to identify footprints of selection.

Changes in gene expression may represent an important mode of human adaptation. However, to date, there are relatively few known examples in which selection has been shown to act directly on levels or patterns of gene expression. In order to test whether single nucleotide polymorphisms (SNPs) that affect gene expression in cis are frequently targets of positive natural selection in humans, we analyzed genome-wide SNP and expression data from cell lines associated with the International HapMap Project. Using a haplotype-based test for selection that was designed to detect incomplete selective sweeps, we found that SNPs showing signals of selection are more likely than random SNPs to be associated with gene expression levels in cis. This signal is significant in the Yoruba (which is the population that shows the strongest signals of selection overall) and shows a trend in the same direction in the other HapMap populations. Our results argue that selection on gene expression levels is an important type of human adaptation. Finally, our work provides an analytical framework for tackling a more general problem that will become increasingly important: namely, testing whether selection signals overlap significantly with SNPs that are associated with phenotypes of interest. [PUBLICATION ABSTRACT]

Opioid drug response and pain perception differs greatly amongst different individuals. The µµ-opioid receptor (MOR) is the main receptor target for important opioid analgesics. As SNPs may contribute to interindividual differences in drug response, signatures of recent positive selection (RPS) were utilized to seek out potentially functional SNPs in the gene in order to facilitate the prioritization of SNPs for evaluation in genetic association studies. Out of over 1000 SNPs at the locus, 184 high-frequency SNPs were interrogated for signatures of RPS. A total of five SNPs (four noncoding and one nonsynonymous coding) demonstrated evidence of RPS. Significantly, the nonsynonymous E1/A118G SNP, which was previously reported to be functionally important, showed evidence of RPS. This reaffirms the feasibility of utilizing signatures of RPS to identify potentially functionally significant SNPs for association studies. Interestingly, the positively selected G allele of this RPS SNP was also predicted to create a novel exon splice enhancer as well as p53 binding sites.

Different signatures of natural selection persist over varying time scales in our genome, revealing possible episodes of adaptative evolution during human history. Here, we identify genes showing signatures of ancestral positive selection in the human lineage and investigate whether some of those genes have been evolving adaptatively in extant human populations. Specifically, we compared more than 11,000 human genes with their orthologs in chimpanzee, mouse, rat, and dog and applied a branch-site likelihood method to test for positive selection on the human lineage. Among the significant cases, a robust set of 11 genes was then further explored for signatures of recent positive selection using single nucleotide polymorphism (SNP) data. We genotyped 223 SNPs in 39 worldwide populations from the HGDP-CEPH diversity panel and supplemented this information with available genotypes for up to 4,814 SNPs distributed along 2 Mb centered on each gene. After exploring the allele frequency spectrum, population differentiation and the maintenance of long unbroken haplotypes, we found signals of recent adaptative phenomena in only one of the 11 candidate gene regions. However, the signal of recent selection in this region may come from a different, neighboring gene (CD5) rather than from the candidate gene itself (VPS37C). For this set of positively selected genes in the human lineage, we find no indication that these genes maintained their rapid evolutionary pace among human populations. Based on these data, it therefore appears that adaptation for human-specific and for population-specific traits may have involved different genes. [PUBLICATION ABSTRACT]

Opioid drug response and pain perception differs greatly amongst different individuals. The micro-opioid receptor (MOR) is the main receptor target for important opioid analgesics. As SNPs may contribute to interindividual differences in drug response, in silico signatures of recent positive selection (RPS) were utilized to seek out potentially functional SNPs in the MOR gene in order to facilitate the prioritization of SNPs for evaluation in genetic association studies. Out of over 1000 SNPs at the MOR locus, 184 high-frequency SNPs were interrogated for signatures of RPS. A total of five SNPs (four noncoding and one nonsynonymous coding) demonstrated in silico evidence of RPS. Significantly, the nonsynonymous E1/A118G SNP, which was previously reported to be functionally important, showed in silico evidence of RPS. This reaffirms the feasibility of utilizing in silico signatures of RPS to identify potentially functionally significant SNPs for association studies. Interestingly, the positively selected G allele of this RPS SNP was also predicted to create a novel exon splice enhancer as well as p53 binding sites.

Wei Zhang1 and M. Eileen Dolan1,2,3 1Section of Hematology/Oncology, Department of Medicine, 2Committee on Clinical Pharmacology and Pharmacogenomics, 3Cancer Research Center, The University of Chicago, IL 60637, U.S.A. Abstract Though debates exist on the early human evolutionary models such as the \"Out of Africa\" theory, which hypothesizes that modern humans migrated from Africa to Europe about 50,000 to 100,000 years ago, Africans and Europeans were geographically separated with minimal gene flow for tens of thousands of years. The variations between the current European and African populations, therefore, should have evolved during this timeframe. To gain more insights into the evolutionary history of human phenotypes including gene expression, it is critical to tell how recent positive selection has played a role in the variations observed in the current populations. Using the list of differentially expressed genes we previously identified between the HapMap samples derived from individuals of African (from Ibadan, Nigeria) and European (from Utah, USA) ancestry, we searched for evidence of selection among these differential genes. We found that 27 differentially expressed genes (out of 356 tested) between these two European and African populations have been under recent positive selection. Our findings suggest that the variation between these two populations appears to be affected primarily by neutral genetic drift and/or stabilizing selection and to a lesser degree by positive selection. Further annotation enrichment analyses showed that these 27 genes under selection were overrepresented in certain Gene Ontology biological processes, molecular functions and cellular components such as transcription, lipid binding and lysosome. Our results can provide unique insights into the evolutionary history of the variation in the gene expression phenotype between these two human populations.

Type IV pili contribute to virulence in Vibrio vulnificus, the bacterium responsible for the majority of fatal seafood-related infections. Here, we performed within- and between-species evolutionary analysis of the gene that encodes the major structural subunit of the pilus, pilA, by comparing it with pilD and gyrB, the genes encoding the type IV prepilin peptidase and [beta] subunit of DNA gyrase, respectively. Although the diversity in pilD and gyrB is similar to each other and likely to have accumulated after speciation of V. vulnificus, pilA is several times more diverse at both nonsynonymous and synonymous levels. Also, in contrast to pilD and gyrB, there are virtually unrestricted and highly localized horizontal movements of pilA alleles between the major phylogenetic groups of V. vulnificus. The frequent movement of pilA involves homologous recombination of the entire gene with no evidence for intragenic recombination between the alleles. We propose that pilA allelic diversity and horizontal movement is maintained in the population by both diversifying and frequency-dependent selection most likely to escape shellfish innate immunity defense or lytic phages. Other possibilities leading to such selection dynamics of V. vulnificus pilA could involve adaptation to diverse host populations or within-host compartments, or natural DNA uptake and transformation. We show that the history of nucleotide diversification in pilA predates V. vulnificus speciation and this diversification started at or before the time of the last common ancestor for V. vulnificus, Vibrio parahaemolyticus, and Vibrio cholerae. At the same time, it appears that within the various pilA groups of V. vulnificus, there is no positive selection for structural mutations and consequently no evidence for source-sink selection. In contrast, pilD has accumulated a number of apparently adaptive mutations in the regions encoding the membrane-spanning portions of the prepilin peptidase, possibly affecting fimbrial expression and/or function, and is being subjected to source-sink selection dynamics. [PUBLICATION ABSTRACT]