Adapting to bubonic plague

 

Rash associated with familial Mediterranean fever (Wikicommons – Dr. H.J. Lachman)

 

In the eastern Mediterranean, people were likelier to survive bubonic plague if they had stronger inflammatory responses to infection in their lungs, gut, and other tissues. Today, that natural selection is attested by a high incidence of familial Mediterranean fever.

 

Familial Mediterranean fever is due to mutations that increase the body’s production of pyrin, a protein that assists inflammatory responses to infection of the lungs, gut, and other tissues. It’s common among eastern Mediterranean peoples, like Jews, Syrians, Armenians, Turks, Greeks, and Italians. The most common symptoms are inflammation of the abdominal lining, the joints, and the chest. Some kind of natural selection seems likely because different mutations have evolved independently to produce the same disease within the same geographic region.

 

Several years ago, Greg Cochran suggested this fever might be an adaptation to trypanosome parasites (Leishmaniasis). Recent research now suggests an adaptation to bacteria of the genus Yersinia. Y. pestis causes bubonic plague, whereas Y. pseudotuberculosis and Y. enterocolitica cause gastroenteritis. These pathogens are highly infectious because they decrease the body’s production of pyrin and thus reduce its ability to fight infection. To compensate for this underproduction of pyrin, there seems to have been selection for mutations that cause overproduction of pyrin, hence the high incidence of familial Mediterranean fever in populations that have coexisted with Yersinia bacteria (Loeven et al. 2020).

 

Yepiskoposyan and Harutyunyan (2007) argue that selection for familial Mediterranean fever must have begun more than 2,500 years ago, since one of the alleles responsible for it is found in different communities of the Jewish diaspora, notably Iraqi and North African Jews. That argument doesn’t convince me, since diaspora communities were not reproductively isolated. The mutation could have arisen in one community and then been spread to others by Jewish individuals moving from one place to another.

 

I’m inclined to believe that selection for this fever began with the earliest recorded outbreak of bubonic plague: the Plague of Justinian (541-549 AD), which killed an estimated 25 million people throughout the Mediterranean Basin and the Middle East. An earlier date is nonetheless possible, since Y. pestis has been attested in archaeological finds as far back as 5,000 years ago (Wikipedia 2022).

 

 

References

 

Chung, L.K., Y.H. Park, Y. Zheng, I.E. Brodsky, P. Hearing, D.L. Kastner, J.J. Chae, and J.B. Bliska. (2016). The Yersinia Virulence Factor YopM Hijacks Host Kinases to Inhibit Type III Effector-Triggered Activation of the Pyrin Inflammasome. Cell Host Microbe 20(3):296-306. https://doi.org/10.1016%2Fj.chom.2016.07.018

 

Cochran, G. (2015). Familial Mediterranean fever. West Hunter, January 9. https://westhunt.wordpress.com/2015/01/09/familial-mediterranean-fever/

 

Loeven, N.A., N.P. Medici, and J.B. Bliska. (2020). The pyrin inflammasome in host-microbe interactions. Curr Opin Microbiol 54:77-86. https://doi.org/10.1016/j.mib.2020.01.005

 

Wikipedia (2022). Bubonic plague. https://en.wikipedia.org/wiki/Bubonic_plague#History

 

Yepiskoposyan, L., and A. Harutyunyan. (2007) Population genetics of familial Mediterranean fever: a review. Eur J Hum Genet 15: 911–916. https://doi.org/10.1038/sj.ejhg.5201869