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Abdeali Jivaji: Why humans wouldn’t exist without giant viruses

Biologist, Abdeali Jivaji from Virginia Tech.
Abdeali Jivaji grows Amoeba to use them to find giant viruses from the environment. Photo courtesy of Abdeali Jivaji.

The following story was written by Abdeali Jivaji as part of Dana Hawley’s Outreach in Biology course.

As a biologist, I am fascinated by the unhinged, no-rules way of nature and by how we are all interconnected in this web of life. I chose to pursue a Ph.D. in Dr. Frank Aylward’s lab in the Department of Biological Sciences at Virginia Tech to learn more about these extraordinary connections of nature.

    I am also fascinated by music, and one of my favorite songs is “Cotton Eyed Joe.” The chorus goes something like this: “Where did you come from, where did you go? Where did you come from, Cotton-Eyed Joe?” These lyrics led me down a path of asking where did WE come from, which has led me to a fascinating theory that has me hooked.

    This is the story about giant viruses and how they led to the emergence of a new type of cell on earth, a cell that had far-reaching consequences for life and led to the creation of both McDonald’s and computers. I am, of course, talking about the eukaryotic cell.

    Life on Earth is generally classified into two groups: prokaryotes and eukaryotes. Prokaryotes include bacteria and archaea, which are primitive, single-celled organisms not visible with just our eyes. Eukaryotes are more modern forms of life that originated after prokaryotes and include everything from single-celled amoeba, to algae, plants, fish, animals, and, of course, humans.

    Life has existed on Earth for more than 3 billion years. Bacteria and archaea are believed to be the first life forms; they dominated the planet for the initial 2 billion years (and still do, in my opinion, but we digress).

    Viruses, although not considered alive by many standards, have grown up on Earth alongside the other living beings. They have influenced us for as long as life has existed. The appearance of giant viruses, however, was the primer for life to really blast.

A picture of different virus size comparisons. Humans having the highest in E. Coli bacterium.
Comparison of giant viruses (blue) with humans, bacteria, and other viruses. Credit: Russell Chun for Quanta Magazine (used with permission).

    Roughly 2 billion years ago, a special type of archaea, called Asgard archaea, engulfed a specific type of bacterial cell. The archaeal cell and bacterial cell both lost their individual identities to become interdependent on each other. This led to the rise of the eukaryotic cell. The archaeal cell became the mothership, whereas the bacterial cell evolved into the powerhouse of the cell: the mitochondria.

    We have multiple lines of scientific evidence that back up this theory. However, the details reveal a lot of inconsistencies that are hard to explain just by the marriage of two cells.

    For starters, both partners lack a nucleus, the compartment inside the modern eukaryotic cell where the genetic material (DNA) is stored. The inconsistencies don’t stop there. The presence of a nucleus presents additional challenges, like having to move materials across the walls. This requires a very large set of specialized proteins; think of it as FedEx for the cell.

    Typically, bacteria and archaea make their proteins in the same general soup of the cell where their DNA is located. That is, the DNA that stores the genetic information is converted to RNA, which acts as the set of directions for ribosomes to make proteins. All of this happens in proximity and in the same space, a process called coupled transcription and translation.

    The presence of a nucleus, which all eukaryotic cells have, forces the cell to decouple this process. The ribosomes (the protein-making factory) are present outside the nucleus, but the RNA is only made inside the nucleus — and then FedEx’d outside.

    These are important innovations in the story of life that are difficult to produce out of thin air. Hmm. . . if only the baby eukaryotic cell did not have to evolve everything from scratch. If only it could just borrow the nucleus and the FedEx machinery from something else. Life would be so easy. . .

    Enter the giant viruses! Well, not exactly, but the great, great ancestors of giant viruses that infected the archaea. A new theory proposed by Philip J. Bell in 2022 in the journal Frontiers of Microbiology addresses the problems posed by the previous theory. We still believe that eukaryotic cells originated from an Asgard archaea and that the mitochondria emerged from the bacteria that entered into a relationship with the baby eukaryotic cell.

    The protagonist in this theory, however, is the virus that infected the Asgard archaea. This was no ordinary infection; it is this infection that gave rise to the nucleus. You see, giant viruses are special and different from other viruses because they contain a lot more of the genes required for day-to-day cellular processes. This makes giant viruses less reliant on the host proteins and able to just use the host cell like a grocery store. Some giant viruses can also create membrane-bound structures, called viral factories, in the cell. These viral factories contain the viral DNA, but transport the directions (the RNA) to make proteins outside of the viral factory. If this sounds familiar, that’s because this is also exactly what a nucleus is responsible for in the modern eukaryotic cell.

    This peculiar infection of a giant virus in an Asgard archaea is believed to have persisted, eventually leading to the merging of the viral and archaeal genome. Thus, the archaeal cell did not have to completely invent its FedEx system from scratch; rather, it simply adopted the FedEx system of the virus for its own purpose. The joining of the bacterium completed the transformation, which enabled me to write this article on an infection 2 billion years later.

    Is this theory final? Like all scientific theories, it requires a lot more evidence to gather momentum — evidence that I, hopefully, will be able to contribute humbly through my research isolating giant viruses from the environment. The only thing of certainty is that giant viruses have been, and will continue to be, extremely important players in the story of life as we know it.

    They may even be able to answer a version of the question posed in Cotton-Eyed Joe: “Where do you come from, where do you go? Where do you come from, Eukaryote?”