Our Genes May Have Mutated to Prevent the Plague, but It May Not Be a Good Thing

Last Week in Medicine

Melih Gönenli
4 min readOct 23, 2022
Y. pestis isolated by Ricardo Jorge during the 1899 Porto plague outbreak — António Plácido da Costa (1848–1916), Public domain, via Wikimedia Commons

The disease caused by Yersinia pestis, which caused more than 50 million deaths in the 14th century, is called the “Black Death” today. Plague, one of the deadliest pandemics with smallpox and measles, still causes 600 cases a year.

This major biological event led to changes in our immune system, and as a result, deaths from plague were significantly prevented. A new study published in Nature has discovered that these mutations led to the largest natural selection in human history.

Klunk et al. have characterized 206 ancient DNA extracts that lived before, during and after the Black Death. They found 245 variants that they thought were associated with the immune system trained for plague. 4 of these 245 variants underwent selection at an unprecedented rate and intensity.

In particular, they showed that these 4 variants are more protective from the plague than those who do not have the variant, cause fewer deaths, and thus cause the inheritance of these variants for generations.

Bubonic plague victims-mass grave in Martigues, France 1720–1721 — S. Tzortzis, Public domain, via Wikimedia Commons

Natural Selection vs. Gene Drift

Natural selection is a process that develops as a result of the occurrence of some genes in populations more than the genes they are superior to over time and the inheritance of these superior genes to new generations. So it takes a long time. For example, peacocks choose their mates based on their tail lengths. Long and shiny tails attract more attention and these mates get ahead of the others in perpetuating their lineage. That’s why male peacocks with short, non-glossy tails are very rare today.

Gene drift is the variation of a gene in a population due to random chance. In other words, it can develop suddenly, unlike natural selection. For example, consider a garden of yellow and blue flowers. If a fire in this garden affects the part of the yellow flowers and only the blue flowers remain, we will see blue dominance in the newly blooming flowers. Gene drift has occurred in the flowers in this garden.

If we compare it to a fire in the garden, the 14th century plague may have caused a gene drift in Europe, leading to the dominance of the genes protecting from the plague.

The Triumph of Death by Pieter Bruegel the Elder — Pieter Brueghel the Elder, Public domain, via Wikimedia Commons

The Exchange: Plague or Other Autoimmune Diseases

Cystic fibrosis (CF) is a genetic disease that develops as a result of the mutation of a protein that enables the glands, tissues and cells that produce secretions such as mucus and sweat in our body to function. Carriage of the gene that causes cystic fibrosis is more common in the Caucasian population. One hypothesis developed as to why this is the case is that the protein mutation seen in CF patients confers a protective feature for tuberculosis disease, therefore it was selected evolutionarily.

Sickle cell anemia is a disease that affects the shape of oxygen-carrying red blood cells. The red blood cells that move away from the disc shape become sickle, cannot pass to small vessels and cannot provide oxygen distribution. This disease is caused by a mutation in the hemoglobin protein found in red blood cells. The onset of sickle cell anemia correlates with malaria disease. For malaria, which causes disease through the bloodstream, intact red blood cells are required. In places where malaria is common, such as Africa, South America, and South Asia, populations have found a way to protect themselves from this disease by developing sickle cell anemia. In other words, they exchanged malaria with sickle cell anemia.

In this article, Klunk et al. also showed that these genes, which were naturally selected for protection from plague, overlap with alleles that currently cause autoimmune diseases such as Crohn’s Disease, Rheumatoid Arthritis, and SLE.

We do not yet know whether other infectious diseases we experienced in the past caused current diseases, but we were able to see this in the case of plague. Cystic fibrosis to ward off tuberculosis, sickle cell anemia to ward off malaria, and other autoimmune diseases to ward off plague. It’s up to you whether it’s a fair trade-off.