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Our view of the universe of genomic regions harboring various types ofcandidate human-specific regulatory sequences (HSRS) has been markedly expandedin 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. Twomajor evolutionary pathways have been identified comprising thousands ofsequences that were either inherited from extinct common ancestors (ECAs) orcreated de novo in humans after human/chimpanzee split. Thousands of HSRSappear inherited from ECAs yet bypassed genomes of our closest evolutionaryrelatives, presumably due to the incomplete lineage sorting and/orspecies-specific loss or regulatory DNA. The bypassing pattern is prominent forHSRS associated with development and functions of human brain. Common genomicloci that may contributed to speciation during evolution of Great Apes comprise248 insertions sites of African Great Ape-specific retrovirus PtERV1 (45.9%; p= 1.03E-44) intersecting regions harboring 442 HSRS, which are enriched forHSRS associated with human-specific (HS) changes of gene expression in cerebralorganoids. Among non-human primates (NHP), most significant fractions ofcandidate HSRS associated with HS expression changes in both excitatory neurons(347 loci; 67%) and radial glia (683 loci; 72%) are highly conserved in Gorillagenome. Modern Humans acquired unique combinations of regulatory sequenceshighly conserved in distinct species of six NHP separated by 30 million yearsof evolution. Concurrently, this unique mosaic of regulatory sequencesinherited from ECAs was supplemented with 12,486 created de novo HSRS. Theseobservations support the model of complex continuous speciation process duringevolution of Great Apes that is not likely to occur as an instantaneous event.

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