标题： 基因组位点中包含59,732个候选人类特异性调控序列的进化起源分析，确定了大猿进化过程中遗传分化模式 显示英文标题

标题： Analysis of evolutionary origins of genomic loci harboring 59,732 candidate human-specific regulatory sequences identifies genetic divergence patterns during evolution of Great Apes

摘要： 我们对包含各种类型候选人类特异性调控序列（HSRS）的基因组区域的宇宙的认识近年来得到了显著扩展。 为了推断包含HSRS位点的进化起源，已对现代人类、黑猩猩、倭黑猩猩、大猩猩、红毛猩猩、长臂猿和食蟹猴基因组中的59,732个位点的保守性模式进行了分析。 已经确定了两条主要的进化途径，包括数千个序列，这些序列要么是从灭绝的共同祖先（ECAs）继承的，要么是在人类与黑猩猩分裂后在人类中全新产生的。 数千个HSRS似乎是从ECAs遗传下来的，但绕过了我们最近的进化亲属的基因组，可能是由于不完全的谱系排序和/或物种特异性丢失或调控DNA。 这种绕过模式在与人类大脑发育和功能相关的HSRS中尤为明显。 可能在大猿进化过程中促进物种形成的共同基因组位点包括248个非洲大猿特异性逆转录病毒PtERV1的插入位点（45.9%；p = 1.03E-44），这些位点交叠于包含442个HSRS的区域，这些HSRS富集于与脑类器官中人类特异性（HS）基因表达变化相关的HSRS。 在非人灵长类动物（NHP）中，与两种兴奋性神经元（347个位点；67%）和放射状胶质细胞（683个位点；72%）中HS表达变化相关的候选HSRS的最大比例在大猩猩基因组中高度保守。 现代人类获得了独特组合的调控序列，这些序列在六种由3000万年进化分隔的不同NHP物种中高度保守。 同时，从ECAs继承的这一独特调控序列镶嵌体还补充了12,486个全新产生的HSRS。 这些观察结果支持了大猿进化过程中复杂连续的物种形成过程模型，这不太可能作为瞬时事件发生。 显示英文摘要

摘要： Our view of the universe of genomic regions harboring various types of candidate human-specific regulatory sequences (HSRS) has been markedly expanded in recent years. To infer the evolutionary origins of loci harboring HSRS, analyses of conservations patterns of 59,732 loci in Modern Humans, Chimpanzee, Bonobo, Gorilla, Orangutan, Gibbon, and Rhesus genomes have been performed. Two major evolutionary pathways have been identified comprising thousands of sequences that were either inherited from extinct common ancestors (ECAs) or created de novo in humans after human/chimpanzee split. Thousands of HSRS appear inherited from ECAs yet bypassed genomes of our closest evolutionary relatives, presumably due to the incomplete lineage sorting and/or species-specific loss or regulatory DNA. The bypassing pattern is prominent for HSRS associated with development and functions of human brain. Common genomic loci that may contributed to speciation during evolution of Great Apes comprise 248 insertions sites of African Great Ape-specific retrovirus PtERV1 (45.9%; p = 1.03E-44) intersecting regions harboring 442 HSRS, which are enriched for HSRS associated with human-specific (HS) changes of gene expression in cerebral organoids. Among non-human primates (NHP), most significant fractions of candidate HSRS associated with HS expression changes in both excitatory neurons (347 loci; 67%) and radial glia (683 loci; 72%) are highly conserved in Gorilla genome. Modern Humans acquired unique combinations of regulatory sequences highly conserved in distinct species of six NHP separated by 30 million years of evolution. Concurrently, this unique mosaic of regulatory sequences inherited from ECAs was supplemented with 12,486 created de novo HSRS. These observations support the model of complex continuous speciation process during evolution of Great Apes that is not likely to occur as an instantaneous event.