Genomic structural variations distinguishing archaic and modern humans are associated with neurodevelopment.

Understanding the divergence in neurodevelopment between extinct archaic hominins and modern humans is a central goal in evolutionary biology. Structural variants (SVs) are key genomic drivers of phenotypic change. Here, we identified a set of SVs present in archaic humans by screening fixed SV events from diverse non-human primate (NHP) lineages, termed archaic hominin structural variants (AHSVs). AHSVs are significantly enriched in genes governing brain development and function, many of which are implicated in neuropsychiatric disorders. We found that several AHSVs overlap with brain cis-regulatory elements (CREs). Furthermore, in three neural-related genes (PDE10A, RAPGEF4, and DCTN4), modern human-specific chromatin loop anchors coincide with deletions shared by archaic hominins, suggesting that AHSVs may have influenced three-dimensional chromatin architecture. Overall, this study expands our understanding of the adaptive evolution of the modern human brain.