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.

种群瓶颈（population bottlenecks）、近亲繁殖（inbreeding）与人工选择（artificial selection），原则上均可影响有害遗传变异（deleterious genetic variation）的水平。然而，上述三类因素对全基因组（genome-wide）有害变异模式的相对重要性，至今仍存在争议。家养与野生犬科动物为探究上述因素对有害变异的影响提供了极佳的研究体系，因其演化历史以已知的种群瓶颈和强烈的人工选择为核心特征。本研究针对90组全基因组序列展开分析，样本涵盖纯种犬、乡村犬与灰狼，以此解析全基因组水平的有害变异模式。研究发现，犬类的非同义突变杂合度与同义突变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，该模式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，而非近期的近亲繁殖。此外，本研究发现，受选择性清除（selective sweeps）影响的基因组区域富集非同义突变变异与孟德尔遗传病基因。据我们所知，本研究首次对与驯化直接相关的有害变异负荷增加量进行了定量估算，其结果对人工选育计划以及珍稀濒危物种保护均具有重要启示意义。具体而言，本研究揭示了人工选育所付出的演化代价，并对“优先选择符合品种标准的个体进行繁殖”这一做法提出了质疑。本研究结果同时表明，相较于单纯避免近亲繁殖，维持较大的种群规模才是阻止有害变异积累的关键因素。