“The question is, how did this adaptive immunity evolve?” Safonova said. “For the very first time, we analyzed five types of gene clusters that control various aspects of immune system production — specifically the building of antibodies and the receptors on another immune cell type known as the T-cell — across 46 mammals to better understand how genetic variation could affect immune function.”
Using an improved version of a computational tool, IgDetective, which Safonova and her coauthors first developed in 2022, researchers scanned, aligned and compared publicly available DNA sequences of 46 mammals of 13 taxonomic orders, such as primates, rodents, bats, carnivores and marsupials, to draw conclusions about how their immune systems evolved.
Researchers found that a decline in adaptive immunity, and possible vulnerability to certain diseases among mammals as a result, was likely caused by genetic bottlenecks: a stark decrease in population over certain periods in history due to factors such as habitat loss or disease.
“Bottlenecks happened during medieval times when humanity was devastated by various diseases like the Black Plague, or when animals suffered widespread habitat loss due to forest fire,” Safonova said. “Species with these past population bottlenecks include felines, aquatic mammals, seals, some primates and ruminants, which are mammals that adapted a special stomach for digesting tough plants.”
Genetic bottlenecks result in limited gene pool diversity for these animals, Safonova explained, which led to possible declining of adaptive immunity.
“Our study showed that the species that underwent population reduction in the past have less diverse adaptive immune genes compared to species with stable populations,” Safonova said. “Studies have suggested that species with less diverse immune genes generate less versatile adaptive immune responses. If this is true, current population bottlenecks may have negative impacts on the survivability of a species in the future.”
In addition to Safonova, the Penn State-affiliated co-authors include Anton Bankevich, assistant professor of computer science; and Anton Zamyatin and Mariia Pospelova, doctoral students in computer science. The other co-authors include Katalin Voss and Matt Pennell of the Department of Computational Biology at Cornell University; Corey Watson of the Department of Computational and Molecular Biology of the Louisville School of Medicine; and Klaus-Peter Koepfli of the Smithsonian-Mason School of Conservation at George Mason University.
The National Institutes of Health’s National Institute of General Medical Sciences supported this research.
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