When you are infected by a virus, the initial defenses your body activates are inherited from our microbial ancestors from billions of years ago. A recent study from The University of Texas at Austin reveals that two essential components of our innate immune system originated from a group of microbes known as Asgard archaea.
When you are infected by a virus, the initial defenses your body activates are inherited from our microbial ancestors from billions of years ago. A recent study from The University of Texas at Austin reveals that two essential components of our innate immune system originated from a group of microbes known as Asgard archaea.
Specifically, two proteins called viperins and argonautes, which are vital in the immune systems of all complex organisms—from insects to plants to humans—originate from Asgard archaea. While bacteria also have versions of these protective proteins, those found in more complex lifeforms are most similar to the ones present in Asgard archaea, according to the recent study published in Nature Communications.
This research supports the theory that all complex life forms, referred to as eukaryotes, evolved from a symbiotic relationship between bacteria and Asgard archaea.
“This strengthens the idea that Asgards are our microbial ancestors,” said Brett Baker, an associate professor of integrative biology and marine science and the senior author. “It shows that not only did eukaryotes inherit many structural proteins from Asgards, but that some of their defense mechanisms also came from Asgards.”
The team discovered a significant array of defense mechanisms in archaea that were previously believed to exist only in bacteria.
When viperins recognize foreign DNA, which may suggest the presence of a harmful virus, they modify the DNA so that the cell can no longer replicate it, effectively preventing the virus from spreading. Similarly, argonautes can cut up foreign DNA, also stopping the virus in its tracks. Moreover, in more complex organisms, argonautes can inhibit the virus from producing proteins through a process known as RNA silencing.
“Viral infections have been an evolutionary challenge since the dawn of life, making the need for some defense strategy essential,” 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 successful defense tools, these were passed down and remain part of our primary defenses.”
The researchers examined immunity-related proteins across various life forms, finding many closely related variations. They employed an AI tool known as ColabFold to predict if proteins with similar amino acid sequences shared similar three-dimensional shapes (essential for their function). This analysis indicated that different versions of the viperin protein likely preserved the same structure and function throughout evolution. They constructed a phylogenetic tree to illustrate the evolutionary connections among these amino acid sequences and their structures.
Lastly, the researchers extracted viperins from Asgard archaea genomes, cloned them into bacteria (to express the proteins), and challenged these bacteria with viruses to demonstrate that Asgard viperins do provide protection. The modified bacteria fared better than those lacking these immune proteins.
“This research underscores the essential role cellular defenses have played since the earliest forms of both prokaryotic and eukaryotic life,” remarked Emily Aguilar-Pine, a former undergraduate researcher involved in the project. “It raises questions about how our current understanding of eukaryotic immunity might be informed by exploring its ancient origins.”
“At this point, it’s clear that Asgard archaea contributed significantly to the complexity observed in modern eukaryotes,” Leão added. “So, it’s reasonable to assume they were also involved in the development of the immune system. We now have strong evidence supporting this assertion.”
Other contributors from UT include Mary Little, Kathryn Appler, Daphne Sahaya, Kathryn Currie, Ilya Finkelstein, and Valerie De Anda.
This research was funded by the Simons and Moore foundations (through the Moore-Simons Project on the Origin of the Eukaryotic Cell) as well as The Welch Foundation.
