Aghikyan, L. | bioRxiv Science

bioRxiv2026

Plague-driven selection enriched familial Mediterranean fever mutations in Armenia

The discovery that positive selection due to resistance to malarial infection maintained the prevalence of sickle cell and other disease alleles was a landmark in evolution, genetics and epidemiology. Mutations in the MEFV gene causing familial Mediterranean fever with high frequency in Eastern Mediterranean populations give the only other strong candidates for a similar process. Here we estimate a pathogenic MEFV mutation burden in Armenians with a carrier rate of ~41%: a worldwide maximum. By combining these data with regional ancient MEFV genotypes spanning more than 60 centuries, we establish that the allele frequencies of three mutations M694V, M680I, and V726A underwent recent rapid increases, indicating positive selection with an onset consistent with the first Yersinia pestis plague pandemic, ~541 CE to 767 CE or even earlier in time, echoing functional data implying resistance to this infection as the selective agent. This extends to three the number of MEFV variants for which there is evidence for strong concurrent selection at this locus in the Eastern Mediterranean, making it unlikely that this geographic peak resulted from chance alone. Although bubonic plague was extremely widespread, the restricted geography of this selection points toward the Eastern Mediterranean as a longstanding enzootic centre with continuous recycling of outbreaks.

genomics↗

bioRxiv2025

Palaeoproteomic and genetic insights into millennial-scale dairy consumption in Armenia

Dairy products are a key component of the diet in Armenia today, yet the origins of milk consumption, its historical development, and genetic adaptations related to milk digestion in the region remain understudied. Here, we investigate the co-evolution of dairying practices and lactase persistence in Armenia through combined palaeoproteomic and genetic analyses spanning from prehistory to the present. Our palaeoproteomic results provide direct evidence for milk consumption in prehistoric Armenia and, in conjunction with existing regional data, indicate that dairying was an established component of the South Caucasus subsistence economy from at least the late fourth millennium BCE. We found evidence of milk consumption from multiple species across archaeological periods, with cattle milk representing the earliest confirmed evidence from the Chalcolithic period. Notably, milk proteins were predominantly recovered from high-altitude sites, suggesting that dairy consumption served as an adaptive strategy for harsh highland environmental conditions. In contrast to the widespread evidence for milk consumption, our genetic findings indicate that the lactase persistence-associated variants never reached high frequencies throughout Armenian prehistory. This pattern suggests that the relatively low frequency of lactase persistence may reflect a predominant cultural adaptation to the fermentation of dairy products, which reduces lactose content and enables dairy use even in genetically lactose-intolerant populations.

evolutionary biology↗