We Owe Our Immunity Boost to Extinct Human Species

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A gene variant has recently been discovered by Australian researchers that indicates our immunity derives from an extinct human species: the Denisovans.

The findings were discovered by teams from the Garvan Institute of Medical Research, Flinders University, and other scientists, who found out our immune system adapts to new and changing environments.

The study was published in Nature Immunology and is the first to point toward one single DNA sequence variant from the Denisovans. This single sequence is responsible for changing the activity of our current human immune system.

Who were the Denisovans?

The Denisovans are an extinct human species that interbred with modern-day humans around 50,000 years ago while the humans were migrating from Africa to Papua New Guinea and Australia.

Today, around five percent of Papua New Guinean blood derives from Denisovan decent.

Thanks to this intermixing of species, we have acquired a gene variant that builds up and increases a range to our immune reactions and inflammation, which include reactions that protect us from microbes.

We Owe Our Immunity Boost to Extinct Human Species and a Gene Variant — This map shows the frequency of the Denisovan TNFAIP3 gene variant in modern human populations of Island South East Asia and Oceania. It is found to be common east of the Wallace Line. *Source: Owen Siggs/Flinders University's College of Medicine and Public Health.*

Associate Professor, Shane Gray, from Garvan, said: "Previous research has found collections of gene variants from extinct human species that appear to have provided an advantage to humans living at high altitudes or to resist viruses, but have been unable to pinpoint which if any were actually functional."

Now, the gene, called TNFAIP3, has been pinpointed. The TNFAIP3 gene creates a protein called A20, which serves to cool our immune system as it reduces immune reactions for molecules and microbes.

How did the team make this discovery?

Working together with the Sydney Children’s Hospital at Randwick, the Children’s Hospital at Westmead, and the Clinical Immunogenomics Research Consortium of Australasia, the Garvan-led study analyzed the genomes of families where a child suffered from an unusual autoimmune or inflammatory condition.

Professor Chris Goodnow, the executive director of the Garvan Institute and co-senior author of the study, said: "Four separate families had the same DNA variant in the TNFAIP3 gene, changing one amino acid in the A20 protein from an isoleucine to a leucine (I207L)."

Ancient human ancestors the Denisovans passed us a key gene that boosted our immune system - Daily Mail https://t.co/AMeJrr3p8x #Denisovan #Denisovans #Asia pic.twitter.com/7YRgaKkZC3
— NUS Trivia | tech news (@NusTrivia) September 19, 2019

Goodnow continued, "However, the presence of this variant in healthy family members indicated it was not sufficient to cause inflammatory disease on its own."

By extracting immune cells from these families' blood samples, the researchers found that these cells created a more powerful inflammatory response that the immune cells of others.

Going back in time

Dr. Owen Siggs, the study's co-first author from Flinders University's College of Medicine and Public Health, studied the TNFAIP3 gene variant on a global scale.

Studying genome sequence data from hundreds of different human populations around the world, the researchers were able to find that the I207L variant was common in people throughout Oceania.

Furthermore, the team also found the I207L variant in the 50,000-year old finger bone of a Denisovan girl in a cave in Siberia.

Dr. Siggs commented that "Making that connection was extremely exciting."

The reason the gene can be attributed to the Denisovans, and not the Neanderthals, for instance, is because the I207L variant was absent from Neanderthals remains from the same cave.