Throughout human history, our species has come into contact with both harmless and infectious microbes that have changed us, like gut bacteria and retroviruses. But more recent infectious disease outbreaks have also left their mark on human biology. New research reported in the American Journal of Human Genetics has suggested that tuberculosis (TB) has had a variety of influences on human biology, including the genome.
"Present-day humans are the descendants of those who have survived many things: climate changes and big epidemics, including the Black Death, Spanish flu, and tuberculosis," noted senior study author Lluis Quintana-Murci of the Institut Pasteur in France. "This work uses population genetics to dissect how natural selection has acted on our genomes."
In this research, the investigators focused on changes in one gene called TYK2, which has been associated with the function of the immune system. Previous work has indicated that a homozygous variant in that gene called P1104A is linked to an increase in the risk of a serious illness due to Mycobacterium tuberculosis.
By assessing a dataset containing genomic information from 1,000 ancient Europeans, the researchers determined that the P1104A variant emerged over 30,000 years ago. Further study that went beyond genomes suggested that the variant became far less frequent around 2,000 years ago. At about that same time, current forms of pathogenic strains of Mycobacterium tuberculosis became prevalent. The P1104A variant has not been linked to other infectious microbes.
"If you carry two copies of this variant in your genome and you encounter Mycobacterium tuberculosis, you are very likely to become sick," said first study author and graduate student Gaspard Kerner. "During the Bronze Age, this variant was much more frequent, but we saw that it started to be negatively selected at a time that correlated with the start of the tuberculosis epidemic in Europe." People that carried this variant were more likely to get TB and die; the variant was therefore less likely to be passed on to children.
"The beauty of this work is that we're using a population genetics approach to reconstruct the history of an epidemic," Quintana-Murci explained. "We can use these methods to try to understand which immune gene variants have increased the most over the last 10,000 years, indicating that they are the most beneficial, and which have decreased the most, due to negative selection."
The tools used in this work may provide insight into other genetic variants that play a role in other infectious diseases.