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• W2894902147 startingPage "432625" @default.
• W2894902147 abstract "Nearly sixty thousand genomic regions harboring various types of candidate human-specific regulatory sequences (HSRS) have been identified using high-resolution sequencing technologies and methodologically diverse comparative analyses of human and non-human primates reference genomes. Here, the systematic analysis of evolutionary origins of 59,732 genomic loci harboring candidate HSRS has been performed to identify genomic sequences that were either inherited from extinct common ancestors (ECAs) or created de novo in human genomes after the split of human and chimpanzee lineages. Present analyses revealed thousands of HSRS that appear inherited from ECAs yet bypassed genomes of our closest evolutionary relatives, Chimpanzee and Bonobo, presumably due to the incomplete lineage sorting and/or species-specific loss or regulatory DNA. The bypassing pattern is particularly prominent for HSRS putatively associated with development and functions of human brain. Significant fractions of retrotransposon-derived loci that are transcriptionally-active in human dorsolateral prefrontal cortex are highly conserved in genomes of Gorilla, Orangutan, Gibbon, and Rhesus (1,688; 1,371; 1,148; and 1,045 loci, respectively), yet they are absent in genomes of both Chimpanzee and Bonobo. These observations were independently corroborated by common evolutionary patterns of 248 insertions sites of African ape-specific retrovirus PtERV1 (45.9%; p = 1.03E-44) intersecting genomic regions harboring 442 HSRS, which are enriched for HSRS that have been associated with human-specific (HS) changes of gene expression in cerebral organoid models of brain development. A prominent majority of genomic regions harboring HS mutations associated with HS gene expression changes during brain development is highly conserved in Chimpanzee, Bonobo, and Gorilla genomes. Among non-human primates (NHP), most significant fractions of candidate HSRS associated with HS gene expression changes in both excitatory neurons (347 loci; 67%) and radial glia (683 loci; 72%) are highly conserved in the Gorilla genome. Present analyses revealed that Modern Humans captured unique combinations of regulatory sequences, divergent subsets of which are highly conserved in distinct species of six NHP separated by 30 million years of evolution. Concurrently, this unique-to-human mosaic of genomic regulatory patterns inherited from ECAs was supplemented with 12,486 created de novo HSRS. Evidence of multispecies evolutionary origins of HSRS support the model of complex continuous speciation process during evolution of Great Apes that is not likely to occur as an instantaneous event." @default.
• W2894902147 created "2018-10-12" @default.
• W2894902147 creator A5083792252 @default.
• W2894902147 date "2018-10-03" @default.
• W2894902147 modified "2023-09-25" @default.
• W2894902147 title "Multi-species mosaicism of evolutionary origins of genomic loci harboring 59,732 human-specific regulatory sequences reflects a complex continuous speciation process of the human lineage" @default.
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