Plague-driven selection enriched familial Mediterranean fever mutations in Armenia
- 1Trinity College Dublin
Abstract
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.
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BibTeX
@misc{hovhannisyan2026plaguedriven,
title = {{Plague-driven selection enriched familial Mediterranean fever mutations in Armenia}},
author = {A. Hovhannisyan and M. Antonosyan and A. Bobokhyan and H. Simonyan and L. Aghikyan and P. Avetisyan and M. Badalyan and H. Simonyan and M. Safaryan and A. Gnuni and A. Piliposyan and A. Grigoryan and M. Simonyan and A. Zaqyan and M. Zardaryan and H. Simonian and L. Mkrtchyan and I. Jackson and E. Breslin and B. Ariano and V. Mattiangeli and Z. Khachatryan and L. M. Cassidy and L. Yepiskoposyan and D. G. Bradley and A. Manica},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.10.750633},
url = {https://www.biorxiv.org/content/10.64898/2026.09.10.750633v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Plague-driven selection enriched familial Mediterranean fever mutations in Armenia
AU - A. Hovhannisyan
AU - M. Antonosyan
AU - A. Bobokhyan
AU - H. Simonyan
AU - L. Aghikyan
AU - P. Avetisyan
AU - M. Badalyan
AU - H. Simonyan
AU - M. Safaryan
AU - A. Gnuni
AU - A. Piliposyan
AU - A. Grigoryan
AU - M. Simonyan
AU - A. Zaqyan
AU - M. Zardaryan
AU - H. Simonian
AU - L. Mkrtchyan
AU - I. Jackson
AU - E. Breslin
AU - B. Ariano
AU - V. Mattiangeli
AU - Z. Khachatryan
AU - L. M. Cassidy
AU - L. Yepiskoposyan
AU - D. G. Bradley
AU - A. Manica
PY - 2026
DA - 2026/09/10
PB - bioRxiv
DO - 10.64898/2026.09.10.750633
UR - https://www.biorxiv.org/content/10.64898/2026.09.10.750633v1
AB - 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.
ER -