A new study led by researchers at the USC Dornsife College of Letters, Arts and Sciences provides a fresh perspective on why people respond differently to infectious diseases. By mapping the history of four specific immune system genes across diverse global populations, the research team found that our modern immune response bears the physical marks of ancient interactions with pathogens from thousands of years ago.
These four genes—IL-4, TLR2, CCL2, and SLC11A1—show signs of natural selection, but the patterns of change differ significantly based on geographic ancestry. Some of these variants even trace back to interbreeding with Neanderthals and Denisovans. This indicates that the traits we rely on today to fight off current illnesses were shaped by ancestral battles with long-forgotten infectious agents.
The team further examined how these genetic signatures relate to COVID-19 by analyzing clinical data from nearly 4,000 patients in Italy. They discovered that rare mutations in the TLR2 gene appear to correlate with more severe cases of the disease. One specific variant was identified more frequently in patients who had previously undergone an organ transplant, which suggests a potential biological link between existing medical risks and genetic susceptibility.
While this research offers a new way to understand individual variations in immune response, the authors emphasize that these results require further validation in larger, more diverse populations. The findings highlight the value of bridging evolutionary biology with clinical research. By understanding how the human immune system evolved, scientists hope to develop better strategies for disease prevention and treatment that account for the unique genetic history of the individual.