Ancestry-inclusive dog genomics challenges popular breed stereotypes.
Ancestry-inclusive dog genomics challenges popular breed stereotypes.
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DOI：
10.1126/science.abk0639
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发表时间：
2022-04-29
期刊：
影响因子：
56.9
通讯作者：
Karlsson, Elinor K.
中科院分区：
文献类型：
--
作者：
Morrill, Kathleen;Hekman, Jessica;Li, Xue;McClure, Jesse;Logan, Brittney;Goodman, Linda;Gao, Mingshi;Dong, Yinan;Alonso, Marjie;Carmichael, Elena;Snyder-Mackler, Noah;Alonso, Jacob;Noh, Hyun Ji;Johnson, Jeremy;Koltookian, Michele;Lieu, Charlie;Megquier, Kate;Swofford, Ross;Turner-Maier, Jason;White, Michelle E.;Weng, Zhiping;Colubri, Andres;Genereux, Diane P.;Lord, Kathryn A.;Karlsson, Elinor K.
在1800年之前，狗可能主要被选择用于功能性角色，如狩猎，守卫和放牧。现代犬种是一个最近的发明，由符合物理理想和血统的纯度定义。品种通常归因于气质和行为倾向的基础上声称的功能的祖先来源人口。推而广之，个别狗的品种血统被认为是气质和行为的预测。通过我们的社区科学项目达尔文的方舟（darwinsark.org），我们招募了一批不同的宠物狗，以探索遗传学如何在这种特殊的自然模式中塑造复杂的行为特征。狗是研究复杂性状遗传学的自然系统。数以百万计的宠物狗生活在人类的家中，分享我们的环境，并接受先进的医疗护理。行为障碍用人类精神药物治疗，达到相似的反应率，遗传研究表明与一些人类精神疾病有共同的病因。我们开发了达尔文的方舟作为一个开放的数据资源，用于收集所有者报告的表型和遗传数据，并邀请任何狗主人登记他们的狗。我们将其与低通测序配对，以捕获该远交群体中几乎所有常见的变异。我们的包容性方法实现了调查复杂性状所需的大样本。我们调查了18,385只狗的主人（49%是纯种狗），并对2155只狗的DNA进行了测序。大多数行为特征是可遗传的[遗传率（h2）> 25%]，但行为只是微妙地区分品种。品种对个体的预测价值很小，只能解释9%的行为变异。对于更易遗传、更容易与品种区分的特征，如服从性（对方向和命令的反应），了解品种血统可以使行为预测更加准确（见图）。对于遗传性较低、品种差异较小的特征，如激动阈值（狗被可怕或不舒服的刺激物激怒的容易程度），品种几乎没有信息。我们使用混血血统的狗来测试品种血统对行为的遗传影响，并将其与纯种狗主人的调查反应进行比较。对于某些特征，例如投标能力和边境牧羊犬血统，我们确认了品种的遗传效应与调查结果一致。对于其他人，比如人类的社交能力和拉布拉多猎犬的血统，我们没有发现明显的影响。通过全基因组关联，我们发现了11个与行为显著相关的区域，包括嚎叫频率和人类社交性，以及136个暗示性区域。与美学特征相关的区域在品种中异常分化，与选择历史一致，但与行为相关的区域则不然。在我们的祖先不同的队列，我们表明，行为特征归因于现代品种是多基因的，环境的影响，并发现，在不同的患病率，在所有品种。我们认为，现代品种的特征行为来自数千年的多基因适应，早于品种形成，与现代品种主要区别于美学特征。通过拥抱狗的多样性，包括纯种狗，混合品种的狗，目的饲养的工作犬，和乡村狗，我们可以充分认识到狗的长期公认的潜力，作为一个自然的模型，遗传发现。品种对行为的影响(A)竞价能力是调查中定义的八个行为因素之一。SE，标准误。(B)某些品种的狗在这个因素上的得分往往比整体狗高或低。（C和D）边境牧羊犬的投标能力平均得分较低（中位数垂直线），但差异很大（C），包括基因确认的边境牧羊犬（D）。(E)在混血狗中，边境牧羊犬的血统对出价有很小的遗传影响。（图片来源：K。Wirka（Sprocket）; M. Wisniewski（Caboose）; B. Hoadley（Molly）; M.洛格斯登（亨特）; A. Macias（Lily）; S.斯台普斯（TWooie）]行为遗传学在狗集中在现代品种，这是孤立的亚群具有独特的物理和，据称，行为特征。我们通过调查18，385只纯种和混合品种狗的主人和2155只狗的基因分型来询问品种刻板印象。大多数行为特征是可遗传的[遗传率（h2）> 25%]，混种犬的混合模式揭示了品种倾向。品种只解释了9%的个体行为变异。全基因组关联分析确定了11个与行为显著相关的基因座，并且特征性的品种行为表现出遗传复杂性。行为位点在品种中并不存在异常的差异，但品种倾向与祖先的功能一致，尽管很弱。我们认为，现代品种的特征行为来自数千年的多基因适应，早于品种形成，与现代品种主要区别于美学特征。现代家犬品种只有160岁，是特定外观特征选择的结果。为了研究遗传学如何与品种特征相一致，莫里尔等人对2000多只纯种和杂交犬的DNA进行了测序。这些数据，再加上业主调查，被用来映射与行为和身体特征相关的基因。虽然许多身体特征与品种有关，但狗的行为在个体之间变化更大。在一般情况下，身体性状遗传力是一个更大的预测品种，但不一定是一个预测品种血统的杂种。在行为特征中，顺从性--狗对人类方向的反应程度--是最容易遗传的，但在狗的个体之间差异很大。因此，狗的品种通常不能很好地预测个人行为，不应用于指导与选择宠物狗相关的决策。-LMZ
Before the 1800s, dogs were probably primarily selected for functional roles such as hunting, guarding, and herding. Modern dog breeds are a recent invention defined by conformation to a physical ideal and purity of lineage. Breeds are commonly ascribed temperaments and behavioral proclivities based on the purported function of the ancestral source population. By extension, the breed ancestry of individual dogs is assumed to be predictive of temperament and behavior. Through our community science project Darwin’s Ark (darwinsark.org), we enrolled a diverse cohort of pet dogs to explore how genetics shapes complex behavioral traits in this exceptional natural model. Dogs are a natural system for investigating the genetics of complex traits. Millions of pet dogs live in human homes, sharing our environment, and receive sophisticated medical care. Behavioral disorders are treated with human psychiatric drugs, achieving similar response rates, and genetic studies suggest shared etiology with some human psychiatric conditions. We developed Darwin’s Ark as an open data resource for collecting owner-reported phenotypes and genetic data and invited any dog owner to enroll their dog. We paired this with low-pass sequencing to capture nearly all common variation in this outbred population. Our inclusive approach achieved the large samples needed to investigate complex traits. We surveyed owners of 18,385 dogs (49% purebred) and sequenced the DNA of 2155 dogs. Most behavioral traits are heritable [heritability (h2) > 25%], but behavior only subtly differentiates breeds. Breed offers little predictive value for individuals, explaining just 9% of variation in behavior. For more heritable, more breed-differentiated traits, like biddability (responsiveness to direction and commands), knowing breed ancestry can make behavioral predictions somewhat more accurate (see the figure). For less heritable, less breed-differentiated traits, like agonistic threshold (how easily a dog is provoked by frightening or uncomfortable stimuli), breed is almost uninformative. We used dogs of mixed breed ancestry to test the genetic effect of breed ancestry on behavior and compared that to survey responses from purebred dog owners. For some traits, like biddability and border collie ancestry, we confirm a genetic effect of breed that aligns with survey responses. For others, like human sociability and Labrador retriever ancestry, we found no significant effect. Through genome-wide association, we found 11 regions that are significantly associated with behavior, including howling frequency and human sociability, and 136 suggestive regions. Regions associated with aesthetic traits are unusually differentiated in breeds, consistent with a history of selection, but those associated with behavior are not. In our ancestrally diverse cohort, we show that behavioral characteristics ascribed to modern breeds are polygenic, environmentally influenced, and found, at varying prevalence, in all breeds. We propose that behaviors perceived as characteristic of modern breeds derive from thousands of years of polygenic adaptation that predates breed formation, with modern breeds distinguished primarily by aesthetic traits. By embracing the full diversity of dogs—including purebred dogs, mixed-breed dogs, purpose-bred working dogs, and village dogs—we can fully realize dogs’ long-recognized potential as a natural model for genetic discovery. Effect of breed on behavior. (A) Biddability is among eight behavioral factors defined from surveys. SE, standard error. (B) Dogs in some breeds tend to score unusually high or low for this factor compared with dogs overall. (C and D) Border collies score lower on average for biddability (vertical line at median) but vary widely (C), including genetically confirmed border collies (D). (E) In mixed-breed dogs, border collie ancestry has a small genetic effect on biddability. [Photo credits: K. Wirka (Sprocket); M. Wisniewski (Caboose); B. Hoadley (Molly); M. Logsdon (Hunter); A. Macias (Lily); S. Staples (TWooie)] Behavioral genetics in dogs has focused on modern breeds, which are isolated subgroups with distinctive physical and, purportedly, behavioral characteristics. We interrogated breed stereotypes by surveying owners of 18,385 purebred and mixed-breed dogs and genotyping 2155 dogs. Most behavioral traits are heritable [heritability (h2) > 25%], and admixture patterns in mixed-breed dogs reveal breed propensities. Breed explains just 9% of behavioral variation in individuals. Genome-wide association analyses identify 11 loci that are significantly associated with behavior, and characteristic breed behaviors exhibit genetic complexity. Behavioral loci are not unusually differentiated in breeds, but breed propensities align, albeit weakly, with ancestral function. We propose that behaviors perceived as characteristic of modern breeds derive from thousands of years of polygenic adaptation that predates breed formation, with modern breeds distinguished primarily by aesthetic traits. Modern domestic dog breeds are only ~160 years old and are the result of selection for specific cosmetic traits. To investigate how genetics aligns with breed characteristics, Morrill et al. sequenced the DNA of more than 2000 purebred and mixed-breed dogs. These data, coupled with owner surveys, were used to map genes associated with behavioral and physical traits. Although many physical traits were associated with breeds, behavior was much more variable among individual dogs. In general, physical trait heritability was a greater predictor of breed but was not necessarily a predictor of breed ancestry in mutts. Among behavioral traits, biddability—how well dogs respond to human direction—was the most heritable by breed but varied significantly among individual dogs. Thus, dog breed is generally a poor predictor of individual behavior and should not be used to inform decisions relating to selection of a pet dog. —LMZ
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影响因子：
3.8
作者：
Arendt, M.;Cairns, K. M.;Ballard, J. W. O.;Savolainen, P.;Axelsson, E.
通讯作者：
Axelsson, E.
影响因子：
9.8
作者：
Boyko AR;Quignon P;Li L;Schoenebeck JJ;Degenhardt JD;Lohmueller KE;Zhao K;Brisbin A;Parker HG;vonHoldt BM;Cargill M;Auton A;Reynolds A;Elkahloun AG;Castelhano M;Mosher DS;Sutter NB;Johnson GS;Novembre J;Hubisz MJ;Siepel A;Wayne RK;Bustamante CD;Ostrander EA
通讯作者：
Ostrander EA
影响因子：
30.8
作者：
Atkinson EG;Maihofer AX;Kanai M;Martin AR;Karczewski KJ;Santoro ML;Ulirsch JC;Kamatani Y;Okada Y;Finucane HK;Koenen KC;Nievergelt CM;Daly MJ;Neale BM
通讯作者：
Neale BM
影响因子：
4.5
作者：
Auton A;Rui Li Y;Kidd J;Oliveira K;Nadel J;Holloway JK;Hayward JJ;Cohen PE;Greally JM;Wang J;Bustamante CD;Boyko AR
通讯作者：
Boyko AR
影响因子：
9.8
作者：
Ajeawung, Norbert F.;Thi Tuyet Mai Nguyen;Campeau, Philippe M.
通讯作者：
Campeau, Philippe M.