Tuberculosis has killed more people than any other disease in the last 2000 years, and it has become much more debilitating, including these patients resting in 1936 opposite the Houses of Parliament of the United Kingdom.
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By Ann Gibbons
Think of the worst plagues of mankind, and the Black Death, the Spanish flu, and COVID-19 all come to mind. Millions of people have died in the deadly pandemics, but their toll has faded compared to that of tuberculosis (TB), which has killed more than 1 billion people over the past 2000 years – and still kills 1.5 million people worldwide. But how and when TB had to become so deadly has long been a mystery.
By detecting the evolution of a gene variant that makes people more susceptible to the disease, researchers have been able to detect the rise and fall of TB over the past 10,000 years – and have shown how it affects the immune system of people living in Iron Age Europe. “We are [all] the descendants of people who survived in the past, ”says author Lluis Quintana-Murci, population geneticist at the Pasteur Institute and the College of France. This paper helps identify “what the real pathogens are 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, shortly after the invention of agriculture. But the variant that kills people today –Mycobacterium tuberculosis—Then 2000 years, when people lived in denser settlements next to domestic animals, reservoirs for TB often emerged.
Two years ago, Gaspard Kerner, a graduate student at the University of Paris, discovered that people are at risk of becoming seriously ill if they become infected with TB if they inherit two copies of a rare variant of the immune gene. TKY2, called P1104A. He realized that by detecting the frequency of the variant in 1013 European genomes of the last 10,000 years, he had a ‘golden’ tool to detect how the immune system develops with TB, says Quintana-Murci, who told Gaspard as a postdoc at the Pasteur Institute.
The researchers found that the P1104A mutation was old – they noticed it in the DNA of a farmer who lived in Anatolia 8500 years ago (which is now Turkey) and calculated that the mutation originated at least 30,000 years ago. has. Anatolian farmers and Yamnaya herdsmen spread this gene variant when they moved to Central Europe. By studying the 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 property. But since then its frequency has dropped to 2.9% – the same rate as among today’s Europeans.
According to ancient DNA studies, the steep jump coincides with the modern variant of TB. Quintana-Murci and his team performed computer simulations on how population size and migration affected the frequency of the gene. They suggest that TB killed a fifth of the two with two specimens of the variant or seriously ill, of which few had 2000 offspring that survived to the end of the Bronze Age. As a result, natural selection has acted strongly and rapidly to eradicate the deadly gene variant to low levels, the researchers reported today in The American Journal of Human Genetics.
“Infectious diseases are the strongest evolutionary pressure humans face,” says Quintana-Murci. Arizona State University, Tempe, molecular anthropologist Anne Stone agrees. The two specimens of the gene variant, she said, “were not good if TB was in the city.”
Stone and other outside researchers say the timing for choosing people and the rise of modern TB fits well. “It’s cool and exciting to see two different lines of data that yield similar results,” says paleogeneticist Kirsten Bos of the Max Planck Institute for Evolutionary Anthropology.
Given new databases such as the UK Biobank and additional ancient DNA samples worldwide, this may be ‘just the beginning’ of studies that track the frequency of variants to understand how our immune systems evolved with specific pathogens, says Sebastien Gagneux, a microbiologist from the Swiss Tropical. and Public Health Institute that were not involved in the study.
But today there is an urgent need to know how wide the P1104A variant is, Kerner says. It is rare in populations tested in India, Indonesia, China and parts of Africa where TB is endemic. But about one in every 600 Britons in the UK Biobank database contains two specimens of the variant. They are at high risk for serious illness or death if exposed to TB, Kerner says.