Highly conserved sequence-specific double-stranded DNA binding networks contributing to divergent genomic evolution of human and chimpanzee brain development

Abstract

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.