Ancient Asgard Archaea May Have Shaped Human Immune Systems

Microbes that appeared billions of years ago may have helped shape the immune systems we possess today.

Fresh research from the University of Texas (UT) indicates that complex organisms such as humans might be less capable of resisting viruses without contributions inherited from our single-celled forebears.

Asgard archaea and the origins of complex life

Before multicellular organisms evolved, Earth was inhabited by a widely distributed group of ancestral microbes.

Scientists first identified the living descendants of these ancient organisms in 2015, using DNA traces collected from the deep ocean between Greenland and Norway. Five years later, researchers succeeded in cultivating these elusive lifeforms in the laboratory for the first time: a superphylum of archaea known as Asgard.

Viewed under a microscope, they initially resemble bacteria. Evolutionarily, however, archaeal cells are more closely related to eukaryotes, including animals and plants, than to their less complex microbial relatives.

Genome evidence has led some researchers to propose that Asgard archaea and the ancestors of eukaryotes diverged roughly 2 billion years ago. That separation ultimately opened the way for all complex life on Earth, including animals, plants, fungi, protists and most algae.

Whatever their shared ancestor was like, it must eventually have acquired a nucleus as part of its basic organisation. Some scientists believe Asgard ancestors may have obtained one from a virus, which created a protective compartment called a viral factory. Mitochria, meanwhile, may have originated when a bacterial ancestor was engulfed.

Little is currently understood about the ways living archaea defend themselves against threats such as bacteria and viruses, making these ideas difficult to investigate in depth.

Asgard archaea immune systems reveal ancient defences

UT researchers have used an artificial intelligence programme to examine a newly enlarged collection of Asgard genomes in search of ancient immune defences.

Their analysis showed that, compared with bacteria, Asgard archaea have developed a diverse range of defence systems, including some that are innate to eukaryotes.

Around 2 percent of all defence systems identified in the analysed Asgard archaea genomes were associated with an immune protein called viperin. This protein counters a broad range of viral infections, apparently by 'silencing' viral reproduction.

Viperin now contributes to the immune systems of every form of complex life on Earth, suggesting that it existed in the last common ancestor shared by archaea and eukaryotes.

The new results indicate that eukaryotic viperins and Asgard viperins are "sister proteins and share a common ancestor".

"It says that not only did eukaryotes get all these rich structural proteins that we've seen before in Asgards," explains integrative biologist Brett Baker from UT, "now it's saying that even some of the defense systems in eukaryotes came from Asgards."

Viperin and argonautes as antiviral tools

Beyond viperin, almost 8 percent of the analysed Asgard archaea defence genes were linked to argonautes. These immune proteins cut up DNA, preventing a virus from spreading.

Across every domain of life on Earth, from archaea and bacteria to eukaryotes, argonautes function as "programmable immune systems".

To assess how these proteins work inside living cells, the researchers cloned genetic instructions for viperins from Asgard archaea genomes into E. coli bacteria. After a virus was introduced, the bacterial cells displayed some evidence of protection.

"Viral infections are one of the evolutionary pressures that we have had since life began, and it is critical to always have some sort of defense," explains Pedro Leão, who carried out the research while working in Baker's laboratory at UT.

"When bacteria and archaea discovered tools that worked, they were passed down and are still part of our first line of defense."

We have microbes to thank.

The study appeared in Nature Communications.