Ancient DNA Reveals How Tuberculosis Shaped the Human Immune System

A new study employing ancient human DNA reveals how tuberculosis has affected European populations over the past 2,000 years.

A 1966 chest x-ray of a tuberculosis patient. (Image courtesy of CDC)

(CN) — While Covid-19 has changed modern life as we know it, infectious diseases have stalked people since modern humans first appeared in Africa 200,000 years ago.

Now a team of scientists are utilizing 21st-century technology to reveal the impact on the human genome of the deadliest killer humans have ever faced: tuberculosis. Employing ancient human DNA, the research reveals how tuberculosis has impacted European populations since the time of Jesus.

Published in the American Journal of Human Genetics, the study has implications for studying not only evolutionary genetics, but also how genetics can influence the immune system.

“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,” said senior author Lluis Quintana-Murci of the Institut Pasteur in France.

Using population genetics to dissect how natural selection has acted on human genomes, scientists focused on a variant of the gene TYK2, called P1104A, which researcher Gaspard Kerner had previously found to be associated with an increased risk of illness after infection with Mycobacterium tuberculosis. 

The results showed which genes predicted who among the population was likely to develop TB, the first infectious disease to spread globally and the deadliest in the common era, killing more than one billion people in the past 2,000 years.

“TB appears to have been more lethal than malaria in the common era,” the study found.

In the 21st century, TB remains a lethal force responsible for more than 1.5 million deaths each year, according to the World Health Organization.

Despite its prevalence, scientists still don’t know the mode and tempo with which TB threatens the human population. The first common, monogenic predisposition resulting from a single defective gene to this deadly pathogen was only identified in 2018.

By studying a dataset of more than 1,000 European ancient human genomes, researchers determined that the P1104A variant first emerged more than 30,000 years ago. DNA evidence suggests a more recent dispersal of M. tuberculosis coinciding with the growth of agricultural communities and human-caused environmental changes that may have helped transmit infectious diseases like TB.

However, the frequency of the genetic variant drastically decreased about 2,000 years ago around the time that present-day forms of infectious Mycobacterium tuberculosis became prevalent.

“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,” Kerner explained.

Researchers hope their use of population genetics to reconstruct the history of an epidemic can advance the study of epidemiology in the future.

“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,” Quintana-Murci said.

Researchers said this type of research can be complementary to other types of immunology studies and also can be used to study the history and implications of genetic variants for other infectious diseases.

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