Past pandemics and disease susceptibility

The COVID-19 pandemic will certainly leave deep traces in the collective conscience. But it may have modified our organisms at a much more microscopic level, as other pandemics seem to have done… Little historical flashback ...

Indeed, a study published at the end of October has studied the impact of various pandemics throughout history on the human genome. Unsurprisingly, infectious diseases are one of the most powerful selection pressures. According to evolutionary theory, selection pressure is defined as “a phenomenon resulting in the evolution of living species under certain environmental constraints”. Genes involved in the immune response would have allowed a positive selection of individuals carrying specific alleles during major pandemics. The scientists behind this article chose to study the most devastating pandemic in human history: the Black Death, which decimated 30 to 50% of the Afro-Eurasian population between 1346 and 1350.
This disease, caused by the bacterium Yersinia pesti, reappeared during the next 400 years in waves, with a mortality generally lower than during Black Death’s first appearance. This phenomenon could be due to a modification of the bacterium, or an adaptation of human organisms! By studying the DNA of individuals who died before, during and after the Black Death, the researchers concluded that four genes would have had "protective" alleles, in particular the ERAP2 gene, coding for endoplasmic reticulum aminopeptidase 2. Individuals homozygous for the protective ERAP2 allele were 40% more likely to survive the Black Death than those homozygous for the other alleles, because it gave them a better ability to limit bacterial proliferation thanks to macrophages.
However, even if this ERAP2 allele protected against the Black Death, it is nowadays a risk factor for autoimmune diseases such as Crohn's disease and rheumatoid arthritis... It seems that an extremely efficient immune system in the Middle Ages would not be adapted today, showing the great importance of the adaptation of organisms to environmental changes throughout history. The next step in this research will be to study the whole genome, not just the genes involved in the immune system... This field of research is a great way to study the mechanisms that have contributed to our survival until today!