Reconstructing the 3D genome organization of Neanderthals reveals that chromatin folding shaped phenotypic and sequence divergence.

ABSTRACT: Changes in gene regulation were a major driver of the divergence of archaic hominins (AHs)-Neanderthals and Denisovans-and modern humans (MHs). The three-dimensional (3D) folding of the genome is critical for regulating gene expression; however, its role in recent human evolution has not been explored because the degradation of ancient samples does not permit experimental determination of AH 3D genome folding. To fill this gap, we apply novel deep learning methods for inferring 3D genome organization from DNA sequence to Neanderthal, Denisovan, and diverse MH genomes. Using the resulting 3D contact maps across the genome, we identify 167 distinct regions with diverged 3D genome organization between AHs and MHs. We show that these 3D-diverged loci are enriched for genes related to the funct

SUBMITTER: McArthur E 

PROVIDER: S-EPMC12424642 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature