Department of Biological Sciences, SUNY at Buffalo.
Genome Biol Evol. 2019 Jun 1;11(6):1679-1690. doi: 10.1093/gbe/evz107.
Polymorphic duplications in humans have been shown to contribute to phenotypic diversity. However, the evolutionary forces that maintain variable duplications across the human genome are largely unexplored. We developed a linkage-disequilibrium based method to detect insertion sites of polymorphic duplications not represented in reference genomes. This method also allows resolution of haplotypes harboring the duplications. Using this approach, we conducted genome-wide analyses and identified the insertion sites of 22 common polymorphic duplications. We found that the majority of these duplications is intrachromosomal and only one of them is an interchromosomal insertion. Further characterization of these duplications revealed significant associations to blood and skin phenotypes. On the basis of population genetics analyses, we found that the duplication of a well-characterized pigmentation-related region, including the HERC2 gene, may be selected against in European populations. We further demonstrated that the haplotype harboring this duplication significantly affects the expression of the HERC2P9 gene in multiple tissues. Our study sheds light onto the evolutionary impact of understudied polymorphic duplications in human populations and presents methodological insights for future studies.
人类中的多态性重复已被证明有助于表型多样性。然而，维持人类基因组中可变重复的进化力量在很大程度上仍未被探索。我们开发了一种基于连锁不平衡的方法来检测参考基因组中未表示的多态性重复的插入位点。该方法还允许解析携带重复的单倍型。使用这种方法，我们进行了全基因组分析，确定了 22 个常见多态性重复的插入位点。我们发现，这些重复的大部分是染色体内的，只有一个是染色体间插入。对这些重复的进一步特征分析显示，它们与血液和皮肤表型存在显著关联。基于群体遗传学分析，我们发现，包括 HERC2 基因在内的一个与色素沉着相关的已充分研究的区域的重复可能在欧洲人群中受到选择压力的影响。我们进一步证明，携带这种重复的单倍型显著影响了多个组织中 HERC2P9 基因的表达。我们的研究揭示了人类群体中研究较少的多态性重复的进化影响，并为未来的研究提供了方法学见解。
