Selection shapes the landscape of functional variation in wild house mice.
Selection shapes the landscape of functional variation in wild house mice.
复制标题
DOI：
10.1186/s12915-021-01165-3
复制
发表时间：
2021-11-19
期刊：
影响因子：
5.4
通讯作者：
Dumont BL
中科院分区：
文献类型：
--
作者：
Lawal RA;Arora UP;Dumont BL
通过过去一万年的人类辅助扩散，家鼠（Mus musculus）最近在全球不同的栖息地中定居，促进了新特征的出现，这些特征在不同的环境中具有适应优势。尽管它们具有首要的哺乳动物模型系统的地位，但这种人口统计和选择历史对野生小鼠种群中疾病相关性状变异的整体模式的影响知之甚少。在这里，我们利用来自不同野生家鼠群体的 154 个全基因组序列来调查功能变异的地理组织并系统地识别正选择信号。我们表明，野生小鼠变异的很大一部分是单一种群所独有的，包括许多预测的功能等位基因。此外，我们报告了与人类复杂疾病和孟德尔疾病相关的许多基因的强烈正选择信号。值得注意的是，我们检测到相对于零期望而言，疾病相关基因的选择信号显着过量，这表明适应在塑造野生小鼠群体功能变异景观中发挥着重要作用。我们还发现了涉及淀粉消化的多个基因的强烈选择信号，包括 Mgam 和 Amy1。我们推测，人鼠共生现象的成功出现可能部分是由于这些位点的饮食适应所促进的。最后，我们的工作揭示了多种神秘的结构变异，这些变异表现为阳性选择的推定信号，强调了全基因组选择扫描中假阳性信号的一个重要且未被充分认识的来源。总的来说，我们的研究结果强调了适应在塑造野生小鼠人类疾病相关基因遗传变异中的作用。我们的工作还强调了野生小鼠遗传多样性的生物医学相关性，并强调了从特定群体中进行有针对性的小鼠采样作为开发罕见和常见人类疾病的有效新小鼠模型的策略的潜力。在线版本包含可在 10.1186/s12915-021-01165-3 获取的补充材料。
Through human-aided dispersal over the last ~ 10,000 years, house mice (Mus musculus) have recently colonized diverse habitats across the globe, promoting the emergence of new traits that confer adaptive advantages in distinct environments. Despite their status as the premier mammalian model system, the impact of this demographic and selective history on the global patterning of disease-relevant trait variation in wild mouse populations is poorly understood. Here, we leveraged 154 whole-genome sequences from diverse wild house mouse populations to survey the geographic organization of functional variation and systematically identify signals of positive selection. We show that a significant proportion of wild mouse variation is private to single populations, including numerous predicted functional alleles. In addition, we report strong signals of positive selection at many genes associated with both complex and Mendelian diseases in humans. Notably, we detect a significant excess of selection signals at disease-associated genes relative to null expectations, pointing to the important role of adaptation in shaping the landscape of functional variation in wild mouse populations. We also uncover strong signals of selection at multiple genes involved in starch digestion, including Mgam and Amy1. We speculate that the successful emergence of the human-mouse commensalism may have been facilitated, in part, by dietary adaptations at these loci. Finally, our work uncovers multiple cryptic structural variants that manifest as putative signals of positive selection, highlighting an important and under-appreciated source of false-positive signals in genome-wide selection scans. Overall, our findings highlight the role of adaptation in shaping wild mouse genetic variation at human disease-associated genes. Our work also highlights the biomedical relevance of wild mouse genetic diversity and underscores the potential for targeted sampling of mice from specific populations as a strategy for developing effective new mouse models of both rare and common human diseases. The online version contains supplementary material available at 10.1186/s12915-021-01165-3.
登录
查看更多内容
影响因子：
4
作者：
Dennis MY;Eichler EE
通讯作者：
Eichler EE
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
1.2
作者：
Cingolani, Pablo;Platts, Adrian;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.
DOI：
10.1073/pnas.1002443107
发表时间：
2010-06-22
影响因子：
11.1
作者：
Beall, Cynthia M.;Cavalleri, Gianpiero L.;Zheng, Yong Tang
通讯作者：
Zheng, Yong Tang
影响因子：
11.4
作者：
Ask, Katrine;Jasencakova, Zuzana;Groth, Anja
通讯作者：
Groth, Anja