Tuberculosis is one of the most deadly infectious diseases in the world, and it is the most deadly disease in Europe's history. It is generally caused by the Mycobacterium tuberculosis bacterium. Scientists have studied the impact of tuberculosis outbreaks on the human genome over the past 10,000 years.
Our genome is partly shaped by natural selection. Genes that increase our chances of survival become proportionally more widespread in the population, and those that are harmful for our health gradually decrease and sometimes even disappear altogether. Population genetics is the study of genetic diversity and its evolution in a given population. "In this case, we used population genetics to piece together the history of an epidemic," explains Lluis Quintana-Murci, Head of the Human Evolutionary Genetics Unit at the Institut Pasteur.
Epidemiology and population genetics
"The generations that went before us survived a great number of threats, including major epidemics such as the Black Death, the Spanish flu and tuberculosis," continues Lluis Quintana-Murci. "We used population genetics to understand the impact of natural selection on our genomes."
Reduction in the frequency of a variant implicated in the response to tuberculosis
The team of scientists studied the evolution of the P1104A variant of the TYK2 gene in Europe. This variant (mutated gene), implicated in the immune response, is associated with an increased risk of falling ill after being infected with Mycobacterium tuberculosis. Using a database of more than a thousand genomes of Europeans that lived over the past 10,000 years, the scientists were able to determine that the variant emerged more than 30,000 years ago. "If an individual with two copies of this variant in their genome came into contact with Mycobacterium tuberculosis, they were highly likely to fall ill," explains Gaspard Kerner, a scientist in the unit and lead author of the study. Surprisingly, around 2,000 years ago, in the Bronze Age, the frequency of the high-risk variant declined sharply. This negative selection, which the scientists believe is one of the most marked in the human genome, correlates with the beginning of the tuberculosis outbreaks in Europe, a period when the current form of Mycobacterium tuberculosis strains became prevalent.
Evolutionary genetics and infectious diseases
As well as advancing knowledge on evolutionary genetics and shedding light on how natural selection and genetics influence the variability of the immune system, these findings also serve as a useful complement to other types of immunological research and provide a basis for studying the role of variants in infectious diseases.
Human ancient DNA analyses reveal the high burden of tuberculosis in Europeans over the last 2,000 years, The American Journal of Human Genetics, March 4, 2021
Gaspard Kerner1,2,3, Guillaume Laval1, Etienne Patin1, Stéphanie Boisson-Dupuis2,3,4, Laurent Abel2,3,4, Jean-Laurent Casanova2,3,4,5,6,8, and Lluis Quintana-Murci1,7,8
1Human Evolutionary Genetics Unit, Institut Pasteur, UMR2000, CNRS, 75015 Paris, France;
2Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Necker Hospital for Sick Children, 75015 Paris, France;
3Paris University, Imagine Institute, 75015 Paris, France;
4St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY 10065, USA;
5Pediatric Hematology-Immunology Unit, Necker Hospital for Sick Children, AP-HP, 75015 Paris, France;
6Howard Hughes Medical Institute, New York, NY 10065, USA;
7Chair of Human Genomics and Evolution, Collège de France, 75005 Paris, France.
8These authors contributed equally