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Adaptive introgression in Tibetans spans focal and distributed architectures

S.-A. Liang, Q. Zhu, X. Gao, Y. Xiao, K. Liu, Z. Xie, L. Deng, X. Ge, B. Su, Q. Fu, Y. Zheng, Y. He, S. Xu, L. Chen

Preprint

In the authors' words

The Denisovan-derived EPAS1 haplotype is a paradigmatic example of adaptive introgression, but whether archaic ancestry contributed beyond such large-effect loci remains unclear. We analyzed genomes from 1,039 Tibetans, Han Chinese, archaic hominins and ancient Tibetan Plateau individuals. Denisovan-derived adaptive variation was highly localized around EPAS1, whereas Neanderthal-derived variation was distributed across the genome; temporal and elevational patterns reinforced this contrast. Despite individual-level heterogeneity, Neanderthal-introgressed gene repertoires repeatedly converged on immune, metabolic and signal-transduction pathways. A Tibetan-enriched Neanderthal PPARGC1A haplotype was associated with lower fasting glucose and showed concordant support from an independent East Asian type 2 diabetes GWAS. These findings reveal that adaptive introgression can contribute to complex human adaptation through functionally convergent combinations of archaic variants, rather than only through shared large-effect haplotypes.

Main resultThe abstract does not state a limitation.

Appeared: Tuesday, September 22. bioRxiv. Preprint, not yet peer-reviewed.

DOI: 10.64898/2026.09.18.752559