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Comparative 3D genomic architectures elucidate the function of the adaptive human-specific inversions in human brain evolution


ABSTRACT: Structural variation (SV) is a class of genetic variants involving long stretches of DNA and provides substantial innovations for adaptation and evolution. Investigation of SV profiles and turnover in nonhuman primates can help answer fundamental questions, such as what makes us uniquely human. Here, we present the high-resolution comparative 3D genome organizations of prefrontal cortex (PFC) of adult human and rhesus macaque. Based on a comprehensive SV atlas in rhesus macaque populations, we found that inversions are selectively constrained from the perspective of 3D genome, those inducing dramatic changes in chromosomal conformation tends to be purged by the action of purifying selection, implying the inconspicuous adaptive roles of inversions associated with strong effects. Furthermore, by integrating comparative genomics and multi-omics data across human and rhesus macaque, such as gene structures, regulatory elements and 3D genomic organizations, we highlighted a category of human-specific inversions with strong effects and found that they had undergone rapid fixation and caused significant changes in gene expression in human brain development, which may represent a driving force in human brain evolution. Overall, our findings reveal the great value of comparative 3D Hi-C maps in elucidating the adaptive functions of structural variants.

ORGANISM(S): Homo sapiens Macaca mulatta

PROVIDER: GSE213693 | GEO | 2024/05/22

REPOSITORIES: GEO

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