Researchers have traced the evolution of a gene variant that makes people more susceptible to tuberculosis and have been able to document the rise and fall of the disease throughout history.
“We are [all] the descendants of people who survived past epidemics,” says author Lluis Quintana-Murci, a population geneticist at the Pasteur Institute and the College of France. This paper helps identify “which are the true pathogens that have changed our DNA and made us more resilient.”
The earliest evidence of TB comes from skeletons buried in the Middle East 9000 years ago, soon after the invention of agriculture. But the variant that kills humans today—Mycobacterium tuberculosis—emerged 2000 years ago, when people lived in denser settlements alongside domesticated animals, often reservoirs for TB.
Two years ago, University of Paris graduate student Gaspard Kerner discovered people were at much higher risk of getting severely ill when infected with TB if they inherited two copies of a rare variant of the immune gene TKY2, called P1104A. He realized that by tracing the frequency of that variant in 1013 European genomes from the past 10,000 years, he had a “golden” tool to detect how the immune gene coevolved with TB, says Quintana-Murci, who hired Gaspard as a postdoc at the Pasteur Institute.
The researchers found that the P1104A mutation was ancient—they spotted it in DNA from a farmer who lived 8500 years ago in Anatolia (what is now Turkey) and calculated that the mutation arose at least 30,000 years ago. Anatolian farmers and Yamnaya herders spread this gene variant as they moved into Central Europe. By studying changes in the frequency of the variant over time, the researchers estimated that about 3% of the population carried the gene until about 5000 years ago. By the middle of the Bronze Age, about 3000 years ago, 10% of Europeans had the trait. But since then, its frequency plummeted to 2.9%—the same rate as among today’s Europeans.