Data from: Bottlenecks and selective sweeps during domestication have increased deleterious genetic variation in dogs

Population bottlenecks, inbreeding, and artificial selection can all, in principle, influence levels of deleterious genetic variation. However, the relative importance of each of these effects on genome-wide patterns of deleterious variation remains controversial. Domestic and wild canids offer a powerful system to address the role of these factors in influencing deleterious variation because their history is dominated by known bottlenecks and intense artificial selection. Here, we assess genome-wide patterns of deleterious variation in 90 whole-genome sequences from breed dogs, village dogs, and gray wolves. We find that the ratio of amino acid changing heterozygosity to silent heterozygosity is higher in dogs than in wolves and, on average, dogs have 2–3% higher genetic load than gray wolves. Multiple lines of evidence indicate this pattern is driven by less efficient natural selection due to bottlenecks associated with domestication and breed formation, rather than recent inbreeding. Further, we find regions of the genome implicated in selective sweeps are enriched for amino acid changing variants and Mendelian disease genes. To our knowledge, these results provide the first quantitative estimates of the increased burden of deleterious variants directly associated with domestication and have important implications for selective breeding programs and the conservation of rare and endangered species. Specifically, they highlight the costs associated with selective breeding and question the practice favoring the breeding of individuals that best fit breed standards. Our results also suggest that maintaining a large population size, rather than just avoiding inbreeding, is a critical factor for preventing the accumulation of deleterious variants.从原理上而言，种群瓶颈（population bottleneck）、近交（inbreeding）与人工选择均可对有害遗传变异（deleterious genetic variation）的水平产生影响。然而，上述三类因素对全基因组（genome-wide）有害变异格局的相对重要性仍存在争议。家养与野生犬科动物（canids）为探究这些因素对有害变异的调控作用提供了绝佳的研究体系，因其演化历史以已知的种群瓶颈和强烈的人工选择为主要特征。本研究针对来自品种犬、村落犬与灰狼的90个全基因组序列，分析了全基因组有害变异的分布格局。研究结果显示，犬类的错义变异杂合度与同义变异杂合度的比值高于灰狼，且平均而言犬类的遗传负荷（genetic load）较灰狼高出2%至3%。多维度证据表明，该格局源于驯化与品种培育过程中伴随的种群瓶颈导致的自然选择效率下降，而非近期近交的影响。此外，本研究发现与选择性清除（selective sweep）相关的基因组区域富集错义变异与孟德尔疾病基因。据我们所知，本研究首次对与驯化直接相关的有害变异遗传负担增量进行了定量估算，该结果对人工选育计划以及珍稀濒危物种的保护均具有重要参考价值。具体而言，本研究揭示了人工选育所伴随的代价，并对"优先选择最契合品种标准的个体开展繁育"的实践提出了质疑。本研究结果还表明，维持较大的种群规模而非仅避免近交，是阻止有害变异积累的关键因素。