Searching for clues to the origins of the eukaryotic immune system

CCurrent hypotheses suggest that all life on Earth evolved from a common ancestor and diversified into the variety of organisms seen today. Scientists have proposed that the eukaryotic branch of this family tree was formed by the fusion of two prokaryotes: ancient bacteria and archaeal cells. symbiotic relationship It is maintained over time.¹

I said, “If this is true.” Pedro Lean“We need to understand what kind of feature this is,” said Archaeobiologist at Radboud University. [archaeal] The host gave rise to the first eukaryotes. ” as a postdoctoral researcher Brett Baker’s In my lab at the University of Texas at Austin, I studied the archaeal origin of eukaryotes, or eukaryotic development.

Leão made the discovery by accident after discovering prokaryotic defense systems with colleagues. Viruses that infect archaea.² He reasoned that archaea, like bacteria, have antiviral mechanisms and that these may be conserved in modern eukaryotes. He began searching the literature for information on the origins of archaeal defense systems and eukaryotic immunity, and made a discovery. perspective paper That piqued his interest. It stated that the immune component of eukaryotes is primarily bacterial, and only briefly mentioned the presence of archaeal defense proteins.³

Leão realized that one reason for this neglect of archaea is that archaeal genomes are poorly represented in the world. the study studied prokaryotes origin Description of eukaryotic defense systems.^4,5 “I thought, ‘Okay, this is an easy job for us to do.’ We can curate a great dataset of archaeal genomes and look for exactly the same thing,” Leão said. I remembered.

He and his colleagues investigated the archaeal defense systems of Asgardian archaea, the closest modern prokaryotes to eukaryotes, and compared their homologies to those of eukaryotes. In a paper published in nature communicationsthe team demonstrated two classes: defense system proteins Those found in archaea are related to those in eukaryotes.⁶ Survey results Provides deeper insight into the origins of the early immune system and its function.

Mr. Leão and his team database Research on prokaryotic defense systems to study the distribution of complete systems in archaeal and bacterial genomes, including Asgardian archaea.⁷ The researchers identified two groups of proteins that are more common in Asgardian archaea than in other archaea and bacteria. They are Argonaute, a protein from the RNA-induced silencing complex, and Viperin (short for viral suppressor protein, endoplasmic reticulum-associated protein, interferon-inducible protein). .

Viper and argonauts Since both are abundant in eukaryotic antiviral defense systems, the researchers compared the similarities of these proteins with those found in Asgard archaea.^8,9 They used the genomes of eukaryotes, archaea, and bacteria to construct a phylogenetic tree and showed that both eukaryotic viperin and argonaute proteins share ancestry with those of Asgardian archaea. was shown. They further confirmed that the structural homology of both proteins, including important functional domains, is conserved between archaea and eukaryotes.

While the common sequence and structural homology of these proteins is promising, Leão sought to further demonstrate that these archaeal proteins function similarly to their eukaryotic counterparts. The research team expressed 48 different Asgard viperin genes. Escherichia coli before introducing bacteriophages to assess viperin activity. Of the proteins generated, 9 were protected Escherichia coli For virus infection prevention. Because some of the sequences are more similar to eukaryotic sequences, the researchers optimized the viperin genes encoding these nine proteins for expression in eukaryotes. Escherichia coliand one additional archaeal viperin showed antiphage activity.

The researchers also found that, on average, Asgardian archaea have a similar number of defense systems per genome as other archaea and bacteria. However, some classes had much lower ratios, such as the genus Heimdallarchia, which is most similar to eukaryotes.

“In my opinion, this is a good hint that there may be a defense system specific to archaea in general,” Léan said. He plans to further investigate archaeal-specific defense systems in his lab. “If we keep looking for archaeal defense systems through homologues of already described bacterial defense systems, we won’t find them.”

buzz baumA cell biologist who studies archaea at the Medical Research Council Institute of Molecular Biology and was not involved in the study, shared this idea. “There may be a lot of things in Asgard that actually work, although we don’t know what they do. [an] Immunology context. ‘He is also excited to learn more about how the archaeal immune system works. “It would be great in the next few years to be able to see in real time how cells use these systems for self-defense.”