Marsden Clare D, Ortega-Del Vecchyo Diego, O'Brien Dennis P, Taylor Jeremy F, Ramirez Oscar, Vilà Carles, Marques-Bonet Tomas, Schnabel Robert D, Wayne Robert K, Lohmueller Kirk E
Department of Ecology and Evolutionary Biology, University of California, Los Angeles, CA 90095;
Interdepartmental Program in Bioinformatics, University of California, Los Angeles, CA 90095;
Proc Natl Acad Sci U S A. 2016 Jan 5;113(1):152-7. doi: 10.1073/pnas.1512501113. Epub 2015 Dec 22.
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、近亲繁殖和人工选择原则上都会影响有害基因变异的水平。然而，这些影响在全基因组有害变异模式中各自的相对重要性仍存在争议。家养和野生犬科动物提供了一个有力的系统来研究这些因素在影响有害变异方面的作用，因为它们的历史主要由已知的瓶颈和强烈的人工选择主导。在这里，我们评估了来自纯种犬、村犬和灰狼的90个全基因组序列中的有害变异全基因组模式。我们发现，犬类中氨基酸改变杂合性与沉默杂合性的比率高于狼，并且平均而言，犬类的遗传负荷比灰狼高2 - 3%。多条证据表明，这种模式是由与驯化和品种形成相关的瓶颈导致的自然选择效率降低所驱动的，而非近期的近亲繁殖。此外，我们发现基因组中与选择性清除相关的区域富含氨基酸改变变异和孟德尔疾病基因。据我们所知，这些结果首次对与驯化直接相关的有害变异增加的负担进行了定量估计，并对选择性育种计划以及珍稀濒危物种的保护具有重要意义。具体而言，它们突出了与选择性育种相关的成本，并对倾向于培育最符合品种标准个体的做法提出了质疑。我们的结果还表明，维持较大的种群规模，而不仅仅是避免近亲繁殖，是防止有害变异积累的关键因素。
