| Title: | Ten millennia of purifying selection on HLA-B27 reveals an ancient epidemic-scale burden of Spondyloarthritis in West Eurasia |
| Journal: | Autoimmunity Reviews |
| Published: | 13 Jul 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42442590/ |
| DOI: | https://doi.org/10.1016/j.autrev.2026.104140 |
Publication 20800
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Abstract
HLA-B27 exemplifies an evolutionary trade-off between protection against infection and susceptibility to inflammatory disease. To investigate its long-term population history, this study examined three HLA-B27-tagging variants-rs116488202, rs4349859, and rs116666910-in present-day populations from UK biobank, 1000 Genomes Project, and the 15,836 ancient West Eurasian individuals. The principal tagging allele reached an estimated frequency of 49.0% approximately 8500 years before present, then declined progressively to 3.9% in the present-day reference population. Comparison with ankylosing spondylitis genome-wide association data showed that HLA-B27-linked alleles conferring increased disease risk had negative selection coefficients, indicating sustained selection against this haplotype over the past 10,000 years. The decline coincided with major Holocene changes in settlement, subsistence, microbial exposure, and enteric infection, which may have increased the inflammatory costs of HLA-B27-associated immunity. Because paleopathology detects mainly advanced skeletal disease, ancient genetic evidence may provide the most sensitive population-level record of this otherwise poorly visible burden. These findings support the hypothesis that HLA-B27-associated spondyloarthritis was sufficiently prevalent and severe to contribute to human genetic evolution in prehistoric West Eurasia.</p>
1 Author
- Ming Zheng
Enabling scientific discoveries that improve human health