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An evolutionary driver of interspersed segmental duplications in primates
Genome Biology ( IF 12.3 ) Pub Date : 2020-08-10 , DOI: 10.1186/s13059-020-02074-4
Stuart Cantsilieris 1, 2 , Susan M Sunkin 3 , Matthew E Johnson 4 , Fabio Anaclerio 5 , John Huddleston 6, 7 , Carl Baker 1 , Max L Dougherty 1 , Jason G Underwood 8 , Arvis Sulovari 1 , PingHsun Hsieh 1 , Yafei Mao 1 , Claudia Rita Catacchio 5 , Maika Malig 1, 9, 10 , AnneMarie E Welch 1, 11 , Melanie Sorensen 1 , Katherine M Munson 1 , Weihong Jiang 12 , Santhosh Girirajan 13 , Mario Ventura 5 , Bruce T Lamb 14 , Ronald A Conlon 12 , Evan E Eichler 1, 15
Affiliation  

Background The complex interspersed pattern of segmental duplications in humans is responsible for rearrangements associated with neurodevelopmental disease, including the emergence of novel genes important in human brain evolution. We investigate the evolution of LCR16a, a putative driver of this phenomenon that encodes one of the most rapidly evolving human–ape gene families, nuclear pore interacting protein ( NPIP ). Results Comparative analysis shows that LCR16a has independently expanded in five primate lineages over the last 35 million years of primate evolution. The expansions are associated with independent lineage-specific segmental duplications flanking LCR16a leading to the emergence of large interspersed duplication blocks at non-orthologous chromosomal locations in each primate lineage. The intron-exon structure of the NPIP gene family has changed dramatically throughout primate evolution with different branches showing characteristic gene models yet maintaining an open reading frame. In the African ape lineage, we detect signatures of positive selection that occurred after a transition to more ubiquitous expression among great ape tissues when compared to Old World and New World monkeys. Mouse transgenic experiments from baboon and human genomic loci confirm these expression differences and suggest that the broader ape expression pattern arose due to mutational changes that emerged in cis. Conclusions LCR16a promotes serial interspersed duplications and creates hotspots of genomic instability that appear to be an ancient property of primate genomes. Dramatic changes to NPIP gene structure and altered tissue expression preceded major bouts of positive selection in the African ape lineage, suggestive of a gene undergoing strong adaptive evolution.

中文翻译:

灵长类动物分散片段重复的进化驱动力

背景人类节段重复的复杂散布模式是与神经发育疾病相关的重排的原因,包括在人类大脑进化中重要的新基因的出现。我们研究了 LCR16a 的进化,LCR16a 是这种现象的推定驱动因素,它编码进化最快的人类-猿基因家族之一——核孔相互作用蛋白(NPIP)。结果比较分析表明,在过去3500万年的灵长类进化过程中,LCR16a在五个灵长类谱系中独立扩增。这些扩展与 LCR16a 侧翼的独立谱系特异性片段重复相关,导致每个灵长类谱系的非直系同源染色体位置出现大的散布重复块。NPIP 基因家族的内含子-外显子结构在灵长类动物进化过程中发生了巨大变化,不同分支显示出特征基因模型,但仍保持开放阅读框。在非洲猿谱系中,我们检测到与旧世界和新世界猴相比,在类人猿组织中向更普遍的表达转变后发生的正选择特征。来自狒狒和人类基因组位点的小鼠转基因实验证实了这些表达差异,并表明更广泛的猿表达模式是由于顺式出现的突变变化而出现的。结论 LCR16a 促进连续散布重复并产生基因组不稳定热点,这似乎是灵长类动物基因组的古老特性。NPIP 基因结构的巨大变化和组织表达的改变发生在非洲猿谱系的主要正选择之前,这表明该基因正在经历强烈的适应性进化。
更新日期:2020-08-10
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