Nature: How the Black Death changed people's immune systems

A new study published in Nature reveals how the immune system of Europeans was affected
by the Black Death.
The Black Death, also known as plague, was a virulent infectious disease
caused by infection with Yersinia pestis.
In the 14th century, about one-third to half of the people in Europe, the Middle East and North Africa died from
the Black Death.

Luis Barreiro of the University of Chicago and Hendrik Poinar of McMaster University in Canada and colleagues write in the paper: "Our study provides strong empirical evidence that the Black Death was an important selective force that shaped the genetic diversity
around certain immune locus.
" ”

The researchers first screened more than 500 ancient samples, which were taken in several cemeteries in and around London or across Denmark
.
It then focused on 206 ancient samples spanning various time points
before, during, and after the Black Death.

Next, they used targeted enrichment capture sequencing to analyze 356 immune-related genes, nearly 500 sites associated with immune diseases as previously identified by GWAS studies, and 250 genome fragments
considered immune "neutral.
"

Of the nearly 250 loci where genetic differentiation occurred, the researchers narrowed it down even further, focusing on the four most differentiated loci in samples before and after the Black Death, which contained genes and variants
associated with Crohn's disease, rheumatoid arthritis and other autoimmune diseases.

"The associated selective advantage is the strongest ever seen in humans, showing how a single pathogen can have a strong impact on the evolution of the human immune system," Barreiro said
.

The researchers specifically mentioned a version of the ERAP2 gene that appeared to be consistent with higher survival rates during the Black Death pandemic
.
They estimated that individuals carrying two copies of the protective ERAP2 allele (rs2549794) had a 40 to 50 percent
higher survival rate after Yersinia pestis infection.

They note, however, that the same variant is associated
with increased susceptibility to Crohn's disease.
"An overactive immune system may have been remarkable in the past, but it may not be as useful
in today's environment.
"

They speculate that the improved survival rate comes from the immune system's ability to more effectively recognize and neutralize the deadly bacteria, as evidenced by
subsequent cell line experiments.
They used macrophage cell lines
expressing rs2549794 or alternative variants.

"When a macrophage encounters a bacterium, it cuts the bacterium into pieces and presents it to other immune cells, indicating the presence of an infection," Barreiro explains
.
"Having this version of the gene seems to create an advantage that strengthens the immune system's ability to
sense invading pathogens.
"

David Enard, an ecology researcher at the University of Arizona in Tucson, published an opinion piece
in the journal Nature.
He noted that even with smaller populations and long intervals between generations, it was possible to adapt at an astonishing rate, but "riding evolutionary high-speed trains comes at a cost.
"

"Going forward, in-depth study of ancient DNA may contribute to a better understanding of the origins of autoimmune diseases," Enard explains, noting that "population migration may shape the risk of
these diseases through 'founder' events.
" ”

Original text search

Klunk, J.
, Vilgalys, T.
P.
, Demeure, C.
E.
et al.
Evolution of immune genes is associated with the Black Death.
Nature (2022).
https://doi.
org/10.
1038/s41586-022-05349-x