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• W2988902862 abstract "Extensive searches for genomic regions harboring various types of candidate human-specific regulatory sequences (HSRS) identified thousands' HSRS using high-resolution next-generation sequencing technologies and methodologically diverse comparative analyses of human and nonhuman primates' (NHPs) reference genomes. In this study, a comprehensive catalogue of 59,732 genomic loci harboring candidate HSRS has been assembled to facilitate the systematic analyses of genomic sequences that were either inherited from extinct common ancestors (ECAs) or created de novo in human genomes. These analyses identified thousands of candidate HSRS and HSRS-harboring loci that appear inherited from ECAs, yet absent in genomes of our closest evolutionary relatives, chimpanzee and bonobo, presumably due to the incomplete lineage sorting and/or species-specific loss or regulatory DNA. This pattern is particularly prominent for HSRS-harboring loci that have been putatively associated with human-specific gene expression changes in cerebral organoid models. A prominent majority of regions harboring human-specific mutations associated with human-specific expression changes during brain development is highly conserved in chimpanzee, bonobo, and gorilla genomes. Among NHPs, dominant fractions of HSRS-harboring loci associated with human-specific gene expression in both excitatory neurons (347 loci; 67%) and radial glia (683 loci; 72%) are highly conserved in the gorilla genome. Analysis of 4433 genes encoding virus-interacting proteins (VIPs) revealed that 95.9% of human VIPs are components of human-specific regulatory networks that appear to operate in distinct types of human cells from preimplantation embryos to adult dorsolateral prefrontal cortex. These analyses demonstrate that modern humans captured unique genome-wide 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. Genes encoding VIPs appear to represent a principal genomic target during evolution of human-specific regulatory networks, which contribute to fitness of Homo sapiens and affect a functionally diverse spectrum of biological and cellular processes controlled by VIP-containing liquid-liquid phase-separated condensates." @default.
• W2988902862 created "2019-11-22" @default.
• W2988902862 creator A5083792252 @default.
• W2988902862 date "2020-01-01" @default.
• W2988902862 modified "2023-09-23" @default.
• W2988902862 title "A Catalogue of 59,732 Human-Specific Regulatory Sequences Reveals Unique-to-Human Regulatory Patterns Associated with Virus-Interacting Proteins, Pluripotency, and Brain Development" @default.
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• W2988902862 doi "https://doi.org/10.1089/dna.2019.4988" @default.
• W2988902862 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31730374" @default.
• W2988902862 hasPublicationYear "2020" @default.
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