Evolution of immune genes is associated with the Black Death 2022 Klunk et al

Abstract
Infectious diseases are among the strongest selective pressures driving human evolution1,2. This includes the single greatest mortality event in recorded history, the first outbreak of the second pandemic of plague, commonly called the Black Death, which was caused by the bacterium Yersinia pestis3. This pandemic devastated Afro-Eurasia, killing up to 30–50% of the population4.

To identify loci that may have been under selection during the Black Death, we characterized genetic variation around immune-related genes from 206 ancient DNA extracts, stemming from two different European populations before, during and after the Black Death. Immune loci are strongly enriched for highly differentiated sites relative to a set of non-immune loci, suggesting positive selection.

We identify 245 variants that are highly differentiated within the London dataset, four of which were replicated in an independent cohort from Denmark, and represent the strongest candidates for positive selection. The selected allele for one of these variants, rs2549794, is associated with the production of a full-length (versus truncated) ERAP2 transcript, variation in cytokine response to Y. pestis and increased ability to control intracellular Y. pestis in macrophages. Finally, we show that protective variants overlap with alleles that are today associated with increased susceptibility to autoimmune diseases, providing empirical evidence for the role played by past pandemics in shaping present-day susceptibility to disease.

Open access, https://www.nature.com/articles/s41586-022-05349-x

 

Selection of Human Immune-Related Genes Was Driven by the Black Death

"In the study, thanks to recent advances in sequencing technology, the scientists examined ancient DNA samples from the bones of over 200 individuals from London and Denmark who died before, during, and after the Black Death plague swept through the region in the late 1340s.

Using targeted sequencing for a set of 300 immune-related genes, they identified four genes that, depending on the variant, either protected against or increased susceptibility to Y. pestis."

"The team further concluded that the selection for rs2549794 is part of the balancing act evolution places upon our genome; while ERAP2 is protective against the Black Death, in modern populations, the same variant is associated with an increased susceptibility to autoimmune diseases, including acting as a known risk factor for Crohn’s disease."

https://neurosciencenews.com/immune-disease-black-death-21678/

 

I read the guardian article about this y'day. Very interesting. https://www.theguardian.com/society/2022/oct/19/gene-black-death-survivors-linked-autoimmune-disease