Intraspecific sequence variation and complete genomes refine the identification of rapidly evolved regions in humans.

Alignment of 20 complete great ape genomes reveals 1,596 rapidly evolved human-specific regions enriched in disease loci and active in brain and heart development.

• Why it matters: Pinpointing genetic changes underlying human phenotypic differences from great apes has been hindered by incomplete reference genomes and reliance on single assemblies, limiting understanding of human evolution.
• What they did: The study aligned 20 telomere-to-telomere assemblies to define Consensus HAQERs, incorporating population variation to distinguish true interspecies divergence from intraspecies variation, and used multiplex single-cell enhancer assays to assess activity.
• The result: Consensus HAQERs show elevated mutation rates, ancient positive selection, and regulatory activity in developing tissues, suggesting they contribute to human-specific gene regulation and disease susceptibility.