According to a study published in BMC Biology, researchers at the USC Dornsife College of Letters, Arts and Sciences and Howard University have discovered that modern human immune responses bear genetic marks of ancient battles with infectious diseases, while also identifying rare variants linked to severe COVID-19. The findings bridge human evolution and infectious disease.
How Ancient Pathogens Shaped Modern Immune Genes
Every time a virus invades a person, it collides with thousands of years of human history. A collaborative study involving USC Dornsife, Howard University, Yale University, and Columbia University traced the evolutionary history of four key immune system genes: IL-4, TLR2, CCL2, and SLC11A1.
Using genetic data from more than 2,000 people representing populations across Africa, Europe, and Asia, researchers analyzed how natural selection favored particular versions of these genes over time. According to the findings, all four genes show signs of natural selection, though pressures varied across geographic populations.
“SARS-CoV-2, the coronavirus that causes COVID-19, may be new, but the immune system it encountered isn’t,” said Michael Campbell, associate professor of biological sciences at USC Dornsife and the study’s senior author. “Our immune genes have been shaped by thousands of generations of encounters with pathogens.”
Did you know? Some of the gene variants identified in modern populations also appear in the DNA of Neanderthals and Denisovans, pointing to ancient interbreeding and shared evolutionary ancestry.
Rare Genetic Variants and Severe COVID-19 Risks
Moving beyond ancient evolutionary markers, the research team investigated whether these immune genes help explain severe COVID-19. Utilizing genetic and clinical information from nearly 4,000 people in Italy from the Italian GEN-COVID study, scientists isolated specific mutations within the TLR2 gene.
The analysis revealed two rare changes in the TLR2 gene. One variant appeared more frequently in COVID-19 patients who had previously received an organ transplant, while the second variant was associated with more severe forms of the disease.
Unlike the common variants shaped by thousands of years of human evolution, these TLR2 variations are rare and appear to be recent genetic mutations. Campbell and his colleagues caution that while organ transplant recipients already face a higher risk of severe illness, these genetic associations require confirmation through larger, independent populations and laboratory validations.
Future Directions in Evolutionary Medicine
Connecting human evolution with infectious disease susceptibility opens new pathways for medical research. By pinpointing genes like TLR2, researchers can better understand the biological basis of infectious disease susceptibility.
“By tracing that evolutionary history, we can better understand why people respond differently to infectious diseases today and identify biological pathways that may inform new strategies for disease prevention and treatment,” Campbell stated.
Alongside Campbell, the study authors include Alessandro Lisi and Marisol Fermin Flores of USC Dornsife; Thomas Heinbockel and Kareem Washington of Howard University; Christopher N. Cross of Howard University and Yale University; and Faith C. Simmonds of Columbia University. The research was supported by the National Institutes of Health, the National Science Foundation, and the National Geographic Society.
Frequently Asked Questions
Did the COVID-19 pandemic create these genetic immune signals?
What genes were analyzed in the study?
The research team analyzed four specific immune genes: IL-4, TLR2, CCL2, and SLC11A1.
How do rare variants differ from common evolutionary variants?
Common variants were shaped over thousands of years by natural selection, whereas the TLR2 variants linked to severe COVID-19 are rare and appear to be recent genetic mutations.
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