Our microbial ancestors developed virus defenses one billion years ago

Next time you manage to dodge a viral attack, you might want to extend a note of gratitude to our ancestors, not the human ones though, but the microbial ones.

It seems the roots of human immunity have been quietly existing for billions of years in the form of two critical defenses, laying its foundation even before complex life birthed itself.

Microbial ancestors with macro roles

The microscopic bodyguards, known as viperins and argonautes, have been functioning as the primary shield against viruses not only in humans but across all complex life forms — from plants to insects.

Tracing their origin back, these proteins have been bestowed upon us by a group of microbes termed Asgard archaea, as per a study from The University of Texas at Austin.

It’s rather intriguing that variations of these defense proteins can also be spotted in bacteria. However, the proteins present in complex life forms have the closest resemblance to those in Asgard archaea.

How Viperins and Argonautes work

How do these microscopic entities fight off giant viruses to keep life forms healthy?

When viperins detect foreign DNA, a hallmark of a potentially harmful virus, they amend the DNA inhibiting the cell from creating more DNA copies, halting the virus in its tracks.

Argonautes, on the other hand, seize foreign DNA and chop it up, effectively limiting the virus.

Beyond that, in more complex organisms, argonautes can obstruct the virus from generating proteins through a process termed RNA silencing.

Whew! Now that’s one impressive microbial defense strategy, isn’t it?

Understanding the microbial ancestors

The game-changing study was headed by Brett Baker, an associate professor of integrative biology and marine science at UT Austin.

“It adds more support to the fact that the Asgards are our microbial ancestors,” Baker noted.

It further substantiates that these Asgard archaea contributed not only to the structural proteins in complex life forms but even some of its defense systems.

The team, for the first time, identified a vast set of defense mechanisms in archaea, previously known only in bacteria. They compared proteins involved in immunity across the tree of life and found several closely related ones.

Using an AI tool named ColabFold, they predicted whether proteins with similar amino acid sequences also boasted similar three-dimensional structures, essential to determining its function.

The findings suggested that variations of the viperin protein likely maintained consistent structures and functions across the tree of life.

Role of Asgard viperins in immunity

The researchers took an extra step to illustrate the effectiveness of Asgard viperins.

They cloned Asgard archaea genomes into bacteria, induced the bacteria to express the proteins, and then exposed the bacteria to viruses.

What they found was truly remarkable — the bacteria with the immune proteins survived better than those without.

Implications for future research

The insights gleaned from the study on viperins and argonautes not only illuminate the ancient origins of our immune defenses but also pave the way for innovative applications in biotechnology and medicine.

Understanding the mechanisms by which these proteins function opens the door to harnessing their capabilities for novel antiviral therapies.

By mimicking or enhancing the action of viperins and argonautes, scientists could potentially develop new strategies to combat viral infections, offering more effective treatment options that are rooted in our own evolutionary history.

Furthermore, the evolutionary continuity of these proteins across diverse life forms suggests that future research may lead to the discovery of additional microbial-derived molecules that could bolster our immune responses, revealing an untapped reservoir of natural defenses waiting to be explored.

As we deepen our comprehension of these ancient mechanisms, we not only honor the legacy of our microbial ancestors but also unlock the potential for transformative advancements in health and medicine.

Viperins, argonautes, and future immunology

All this research points to an exciting possibility – the key to understanding modern eukaryotic immunity might just lie in uncovering its most ancient origins.

“It’s undeniable at this point that Asgard archaea contributed a lot to the complexity that we see in eukaryotes today,” said Pedro Leão, a former postdoctoral researcher in Baker’s lab and now an assistant professor at Radboud University in the Netherlands.

So, next time you escape a dreaded viral attack, you know who to thank! Fascinating isn’t it, how our complex immune system has inherited such powerful defenses from these ancient microorganisms?

Now let the thought marinate and who knows, you might be the next person to uncover another intriguing piece of the colossal immunity puzzle.

This work was supported by the Simons and Moore foundations (via the Moore-Simons Project on the Origin of the Eukaryotic Cell) and The Welch Foundation.

The study is published in the journal Nature Communications.

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