Fixed human pangenome sequences reveal origins of common human traits

Humans possess human-specific traits ^1,2 such as spoken language and lineage-specific traits such as ape-specific taillessness ^3,4 . Previous efforts to identify the DNA sequences responsible for such human traits were limited by necessary accommodations for poor genome assembly quality and lack of population genomic sampling ^5–16 . Here, we implement new algorithms that combine the near-complete human reference pangenome alignment with a new near-complete simian cross-species alignment to define human- and lineage-specific DNA sequences fixed across human haplotypes. Previously reported FOXP2/NOVA1 ^17,18 amino acid substitutions linked to human spoken language and TBXT transposable element insertion contributing to ape taillessness ^3,4 were unique to their respective clades and fixed in sampled humans. In contrast, widely used sets of candidate human-mutated loci showed limited enrichment for either human specificity or fixation. Integration with candidate cis -regulatory elements ^19–22 identified putative regulatory sequences specific to humans and linked to human-specific traits like hair reduction ^23,24 and brain transcriptome patterning ²⁵ . Although brain-associated fixed regulatory changes were present in all lineages, enrichment for spoken language was human-specific and enrichment for receptive language was ape-specific. This study provides a new pangenome-aware comparative framework and catalogs of candidate genomic loci to trace the evolutionary origins of common human traits and disease risks.