A study led by researchers at the USC Dornsife College of Letters, Arts and Sciences and Howard University suggests that some genes involved in the body's immune response today bear marks from ancient battles with infectious diseases, according to an Aug. 3 report.
The research identified rare genetic variants that may help explain why some people developed more severe COVID-19 than others. The findings connect human evolution and infectious disease, fields rarely studied together. By tracing the evolutionary history of four immune system genes previously linked to respiratory or inflammatory diseases across global populations, the team examined whether changes in those genes were linked to severe COVID-19 in nearly 4,000 people in Italy using data from the Italian GEN-COVID study.
Michael Campbell, associate professor of biological sciences at USC Dornsife and senior author of the study, said understanding how evolution shaped the immune system over thousands of years offers a new way to think about why people respond differently to disease today. To explore this history, scientists analyzed four genes—IL-4, TLR2, CCL2 and SLC11A1—using genetic data from more than 2,000 individuals representing populations from Africa, Europe and Asia. They found evidence that all four genes had been shaped by natural selection but not uniformly across populations.
Some gene variants were also found in DNA from Neanderthals or Denisovans. In some cases these similarities likely reflect inherited DNA from a shared ancestor; in others they point to ancient interbreeding between early modern humans and extinct relatives. Campbell said these evolutionary changes happened long before coronavirus emerged: "The signals we found weren't created by COVID-19," he said. "They reflect much older evolutionary pressures, probably from infectious diseases our ancestors faced over thousands of years."
Researchers then looked for links between these immune genes and severe COVID-19 outcomes using clinical information from nearly 4,000 Italians who tested positive for COVID-19. They identified two rare changes in the TLR2 gene: one was more common among patients who had received organ transplants; another was associated with more severe forms of illness.
The authors caution that their findings should be interpreted carefully, since genetic associations need confirmation in larger independent groups as well as laboratory validation. They also note future studies should include more genetically diverse populations worldwide.
