title: Bottlenecks and selective sweeps during domestication have increased deleterious genetic variation in dogs.
abstract: 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.
authors.affiliation: Department of Ecology and Evolutionary Biology, University of California, Los Angeles, CA 90095;
authors.forename: Clare D
authors.initials: CD
authors.lastname: Marsden
authors.affiliation: Interdepartmental Program in Bioinformatics, University of California, Los Angeles, CA 90095;
authors.forename: Diego
authors.initials: D
authors.lastname: Ortega-Del Vecchyo
authors.affiliation: Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO 65211;
authors.forename: Dennis P
authors.initials: DP
authors.lastname: O'Brien
authors.affiliation: Division of Animal Sciences, University of Missouri, Columbia, MO 65211;
authors.forename: Jeremy F
authors.initials: JF
authors.lastname: Taylor
authors.affiliation: Institut Catala de Recerca i Estudis Avançats, Institut de Biologia Evolutiva (Centro Superior de Investigaciones Cientificas-Universitat Pompeu Fabra), 08003 Barcelona, Spain;
authors.forename: Oscar
authors.initials: O
authors.lastname: Ramirez
authors.affiliation: Conservation and Evolutionary Genetics Group, Estación Biológica de Doñana-Consejo Superior de Investigaciones Cientificas, 41092, Seville, Spain;
authors.forename: Carles
authors.initials: C
authors.lastname: Vilà
authors.affiliation: Institut Catala de Recerca i Estudis Avançats, Institut de Biologia Evolutiva (Centro Superior de Investigaciones Cientificas-Universitat Pompeu Fabra), 08003 Barcelona, Spain; Centro Nacional Analasis Genomico, 08023, Barcelona, Spain;
authors.forename: Tomas
authors.initials: T
authors.lastname: Marques-Bonet
authors.affiliation: Division of Animal Sciences, University of Missouri, Columbia, MO 65211; Informatics Institute, University of Missouri, Columbia, MO 65211;
authors.forename: Robert D
authors.initials: RD
authors.lastname: Schnabel
authors.affiliation: Department of Ecology and Evolutionary Biology, University of California, Los Angeles, CA 90095;
authors.forename: Robert K
authors.initials: RK
authors.lastname: Wayne
authors.affiliation: Department of Ecology and Evolutionary Biology, University of California, Los Angeles, CA 90095; Interdepartmental Program in Bioinformatics, University of California, Los Angeles, CA 90095; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095 klohmueller@ucla.edu.
authors.forename: Kirk E
authors.initials: KE
authors.lastname: Lohmueller
mesh_terms: D000818:Animals; D000829:Animals, Domestic / Q000235:genetics*; D066264:Datasets as Topic; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs / Q000235:genetics*; D056727:Endangered Species; D014644:Genetic Variation; D016678:Genome / Q000235:genetics; D006579:Heterozygote; D007178:Inbreeding; D011156:Population Density; D012641:Selection, Genetic; D000068618:Selective Breeding / Q000235:genetics*; D019596:Wolves / Q000235:genetics
keywords: bottleneck; deleterious mutations; domestication; selective sweep