When you get infected with a virus, some of the first weapons your body deploys to fight it were passed down from microbial ancestors billions of years ago. According to new research from The University of Texas at Austin, two key elements of our innate immune system came from a group of microbes called Asgard archaea.
Specifically, viperins and argonautes, two proteins that play important roles in the immune systems of all complex life—from insects to plants to humans—originated from the Asgard archaea. Versions of these defense proteins are also present in bacteria, but those in complex life forms are most closely related to those in Asgard archaea, according to a study published in Nature Communications.
This research supports the idea that all complex life, known as eukaryotes, arose from a symbiotic relationship between bacteria and Asgard archaea.
“It adds more support to the fact that the Asgards are our microbial ancestors,” said Brett Baker, associate professor of integrative biology and marine science and senior author. “It says that not only did eukaryotes get all these rich structural proteins that we’ve seen before in Asgards; now it’s saying that even some of the defense systems in eukaryotes came from Asgards.”
The researchers identified for the first time a large arsenal of defense systems in archaea previously known only in bacteria.
When viperins detect foreign DNA indicating a dangerous virus, they edit the DNA so that the cell can no longer replicate it, stopping viral spread. When argonautes detect foreign DNA, they chop it up, halting viral activity. In more complex organisms, argonautes can block viruses from making proteins through RNA silencing.
“Viral infections are one of the evolutionary pressures we have had since life began, and it is critical always to have some sort of defense,” said Pedro Leão, now an assistant professor at Radboud University in the Netherlands and a recent postdoctoral researcher in Baker’s lab. “When bacteria and archaea discovered tools that worked, they were passed down and are still part of our first line of defense.”
The researchers compared immunity-related proteins across various life forms and found many closely related ones. They used an AI tool called ColabFold to predict whether similar amino acid sequences had similar three-dimensional shapes. This analysis showed that variations of viperin likely maintained consistent structure and function across different species. They then created a phylogeny showing evolutionary relationships among these proteins.
Finally, they took viperins from Asgard archaea genomes, cloned them into bacteria (so they would express these proteins), challenged them with viruses, and demonstrated that Asgard viperins provided protection. These modified bacteria survived better than those without these immune proteins.
“This research highlights the integral role cellular defenses must have played from the beginning of both prokaryotic and eukaryotic life,” said Emily Aguilar-Pine, a former undergraduate researcher who contributed to the project. “It also inspires questions about how our modern understanding of eukaryotic immunity can benefit from unraveling some of its most ancient origins.”
“It’s undeniable at this point that Asgard archaea contributed significantly to the complexity we see in eukaryotes today,” Leão said. “So why wouldn’t they also be involved in the origin of the immune system? We have strong evidence now that this is true.”
Other authors include Mary Little, Kathryn Appler, Daphne Sahaya, Kathryn Currie, Ilya Finkelstein and Valerie De Anda—all affiliated with UT Austin.
This work was supported by Simons Foundation and Moore Foundation (via Moore-Simons Project on Origin Eukaryotic Cell) as well as The Welch Foundation.
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