高度保守的序列特异性双链 DNA 结合网络促成了人类和黑猩猩大脑发育的基因组进化差异

Gennadi Glinsky
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摘要

据报道,在哺乳动物的进化过程中,出现了基因组调控网络的一致性和差异性特征,这些网络包括 716 个蛋白质的转录因子结合位点(TFBS)序列阵列,它们无处不在,在质量上几乎相同,但在数量上却各不相同。构成这些网络蛋白质成分的绝大多数 TFs(716 个中的 770 个;98%)似乎具有基因本体(Gene Ontology,GO)的共同特征,即序列特异性双链 DNA 结合(GO:1990837)。对 17,935 个 ATAC-seq 定义的脑发育调控区(BDRRs)进行的全基因组和单个染色体水平的分析表明,这些网络中的 TF 成分的 TFBS 几乎具有普遍的代表性,与黑猩猩相比,现代人的数千个 BDRRs 中的 TFBS 密度似乎一直较高。包括LTR/HERV、SINE/Alu、SVA和LINE家族在内的可转座元件(TE)似乎包藏并传播着这里所发现的高度保守的序列特异性双链DNA结合网络的全基因组共识调控节点,其中的TFBS面板选择表现出个体染色体特异性特征和物种特异性分化模式。总之,本研究报告中的观察结果突显了由 TE 编码的人类基因组 DNA 序列在提供全基因组高度保守序列特异性双链 DNA 结合网络的调控种子模板方面具有以前未曾认识到的重要功能,这很可能有助于人类和黑猩猩大脑发育的持续差异基因组进化。
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Highly conserved sequence-specific double-stranded DNA binding networks contributing to divergent genomic evolution of human and chimpanzee brain development
Emergence during mammalian evolution of concordant and divergent traits of genomic regulatory networks encompassing ubiquitous, qualitatively nearly identical yet quantitatively distinct arrays of sequences of transcription factor binding sites (TFBS) for 716 proteins is reported. A vast majority of TFs (770 of 716; 98%) comprising protein constituents of these networks appear to share common Gene Ontology (GO) features of sequence-specific double-stranded DNA binding (GO: 1990837). Genome-wide and individual chromosome-level analyses of 17,935 ATAC-seq-defined brain development regulatory regions (BDRRs) revealed nearly universal representations of TFBS for TF-constituents of these networks, TFBS densities of which appear consistently higher within thousands BDRRs of Modern Humans compare to Chimpanzee. Transposable elements (TE), including LTR/HERV, SINE/Alu, SVA, and LINE families, appear to harbor and spread genome-wide consensus regulatory nodes of identified herein highly conserved sequence-specific double-stranded DNA binding networks, selections of TFBS panels of which manifest individual chromosome-specific profiles and species-specific divergence patterns. Collectively, observations reported in this contribution highlight a previously unrecognized essential function of human genomic DNA sequences encoded by TE in providing genome-wide regulatory seed templates of highly conserved sequence-specific double-stranded DNA binding networks likely contributing to continuing divergent genomic evolution of human and chimpanzee brain development.
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