USC Dornsife and Howard University Study Links Ancient Genes to Severe Covid

Connecting Human Evolution and Infectious Disease

The study integrates the fields of infectious disease and human evolution, two areas that are rarely examined together. According to USC Dornsife, this multidisciplinary approach allowed scientists to uncover clues that might have been missed if the fields were studied in isolation.

To investigate how ancient diseases shaped the immune system, scientists from USC Dornsife and Howard collaborated with researchers from Columbia and Yale universities. The team analyzed four specific genes that regulate the body’s immune response:

• SLC11A1
• CCL2
• TLR2
• IL-4

The researchers analyzed genetic data from more than 2,000 people from Asia, Europe, and Africa to find evidence of natural selection favoring specific versions of these genes over time. They determined that all four genes had been shaped by natural selection, though the effects varied across different global populations.

Ancient DNA and Extinct Human Relatives

The research revealed that some of these gene variants are present in the DNA of Denisovans or Neanderthals, extinct human relatives from tens of thousands of years ago. The study notes that these similarities may result from inherited DNA from a shared ancestor or from ancient interbreeding between early modern humans and these extinct relatives.

Michael Campbell, the study’s senior author and associate professor of biological sciences at USC Dornsife, stated that these evolutionary changes occurred long before the emergence of the coronavirus. The signals we found weren’t created by COVID-19, Campbell said, noting that they reflect older evolutionary pressures from diseases ancestors faced over thousands of years.

Rare Variants and COVID-19 Severity

The research team used the Italian GEN-COVID study to examine whether changes in these genes linked to severe COVID-19, analyzing genetic and clinical data from nearly 4,000 people in Italy who tested positive for the virus. Through this process, researchers identified two rare changes in the TLR2 gene.

According to Miragenews, these TLR2 variants differ from common variants shaped over millennia because they appear to be much more recent genetic mutations. The study found that:

• One rare variant was more frequent in COVID-19 patients who had previously undergone an organ transplant compared to other patients.
• A second variant was associated with more severe forms of COVID-19, suggesting it may contribute to why some people become more seriously ill.

Implications for Future Research

Campbell observed that while SARS-CoV-2 is a new virus, the immune system it encounters has been shaped by thousands of generations of encounters with pathogens. He stated, The pathogens our ancestors encountered thousands of years ago helped shape the immune system we carry today.

By identifying immune genes like TLR2 that were shaped by ancient diseases, scientists may find new clues regarding the biological basis of susceptibility to infectious diseases. The researchers emphasized the necessity of including more genetically diverse populations in future studies to improve the global understanding of disease risk.