The 12th International Symposium on 3D Genomics

50 / 2026-03-31 19:39:30

Introgressed mitochondrial fragments from archaic hominins alter nuclear genome function in modern humans

NUMT, archaic admixture, positive selection, evolution, 3D genome architecture

Archaic introgression introduced functionally relevant variants into modern humans, yet small-scale insertions remain understudied. Here, we leverage 2,519 modern human genomes and four high-coverage archaic hominin genomes to systematically characterize nuclear mitochondrial DNA segments (NUMTs). We uncover 483 polymorphic NUMTs across globally diverse human populations and 10 in archaic genomes. By combining overlap with Neanderthal- and Denisovan-derived haplotypes, phylogenetic analyses, insertion time estimates, and haplotype co-localization, we identify five NUMTs introduced into modern humans via archaic hominin introgression. Functional analyses reveal that introgressed NUMTs can modulate gene expression, including allele-specific upregulation of the immune-related gene RASGRP3, and reshape 3D chromatin structure at loci such as SCD5 and HNRNPD. These findings highlight an underappreciated mechanism by which archaic mitochondrial fragments shape nuclear genome function and evolution. Our study reframes NUMTs not as passive genomic fossils but as dynamic elements influencing modern human diversity and adaptation.