An evolutionary driver of interspersed segmental duplications in primates
An evolutionary driver of interspersed segmental duplications in primates
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DOI：
10.1186/s13059-020-02074-4
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发表时间：
2020-08-10
期刊：
影响因子：
12.3
通讯作者：
Eichler, Evan E.
中科院分区：
文献类型：
--
作者：
Cantsilieris, Stuart;Sunkin, Susan M.;Eichler, Evan E.
人类片段复制的复杂穿插模式负责与神经发育疾病相关的重排，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被认为是这种现象的驱动因素，它编码了进化最快的人类-类人猿基因家族之一，核孔相互作用蛋白（NPIP）。结果对比分析表明，LCR16a基因在过去3500万年的灵长类进化过程中，在5个灵长类谱系中独立扩展。这种扩增与LCR16a侧翼的独立谱系特异性片段复制有关，导致在每个灵长类谱系的非同源染色体位置出现大的分散复制块。NPIP基因家族的内含子-外显子结构在灵长类动物的进化过程中发生了巨大的变化，不同的分支显示出独特的基因模型，但仍保持开放的阅读框。在非洲猿类谱系中，与旧大陆和新大陆的猴子相比，我们发现了在类人猿组织中向更普遍的表达过渡后发生的积极选择的特征。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cis中出现的突变变化而产生的。结论LCR16a促进了序列的分散重复，并产生了基因组不稳定的热点，这似乎是灵长类基因组的一个古老特性。在非洲猿类谱系中，toNPIPgene结构的剧烈变化和组织表达的改变先于重大的积极选择，表明该基因经历了强烈的适应性进化。
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 toNPIPgene structure and altered tissue expression preceded major bouts of positive selection in the African ape lineage, suggestive of a gene undergoing strong adaptive evolution.