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