Genome-Wide Footprints of Pig Domestication and Selection Revealed through Massive Parallel Sequencing of Pooled DNA

BackgroundArtificial 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.Methodology/Main FindingsGenome 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.Conclusions/SignificanceThese 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.【背景】人工选择已促使驯化物种发生快速演化。对驯化物种全基因组范围内选择印记的鉴定，有助于揭示表型多样性的遗传基础。【方法与主要发现】本研究针对野猪以及4个以肌肉发育、生长、行为和被毛颜色为强选择目标的家猪品种（大约克夏（Large White）、长白猪（Landrace）、杜洛克（Duroc）和皮特兰（Pietrain）），对占基因组约2%的混合简化基因组文库（pooled reduced representation libraries, RRL）开展大规模平行测序（massive parallel sequencing），以此鉴定猪驯化与选择的全基因组范围印记。研究采用专门开发的、可校正DNA混合、低平均测序深度以及测序误差的统计方法，对猪的全基因组核苷酸多样性（nucleotide diversity）与遗传分化（genetic differentiation）进行了估算。本研究发现了大量暗示正选择（positive selection）与平衡选择（balancing selection）的信号，其中以皮特兰最为显著——该品种是针对肌肉发育进行高强度选择的家猪品种之一。多数选择信号为群体特异性，但受影响的基因组区域所富集的基因，均归属于被毛颜色、脑发育、肌肉发育、生长、代谢、嗅觉与免疫等常见生物学功能类别。在与肌肉发育和生长相关的基因所在区域，品种间的遗传分化程度高于单个品种与野猪之间的遗传分化程度。【结论与意义】本研究结果表明，尽管不同驯化品种经历了相似的选择压力，但选择所靶向的基因并不相同。这一现象可能反映了欧洲家猪的多次独立驯化事件，或是后续亚洲等位基因基因渐渗（introgression）的结果。整体而言，研究估算约有7%的猪基因组受到选择事件的影响。本研究证实，基因组混合样本的大规模平行测序是一种经济高效的选择印记鉴定方法。