Ancient viruses that infected vertebrates hundreds of millions of years ago played a key role in the evolution of our advanced brains and large bodies, a study said Thursday.
The study, published in the journal Cell, examines the origins of myelin, an insulating layer of fatty tissue that forms around nerves and allows electrical impulses to travel faster.
According to the authors, a gene sequence acquired by retroviruses—viruses that invade their host’s DNA—is crucial for the production of myelin, and this code is now found in modern mammals, amphibians and fish.
“The thing that I find most remarkable is that all the diversity of modern vertebrates that we know of and the size that they have reached: elephants, giraffes, anacondas, bullfrogs, condors, would not have happened,” senior author and neuroscientist Robin Franklin of Altos Labs-Cambridge Science Institute told AFP.
A team led by Tanai Ghosh, a computational biologist and geneticist at the Franklin Lab, searched genomic databases to try to find the genetics likely to be related to the cells that make myelin.
In particular, he was interested in studying mysterious “non-coding regions” of the genome that have no obvious function and were once dismissed as junk but are now recognized to have evolutionary significance.
Ghosh’s search focused on a specific sequence derived from an endogenous retrovirus that has long lurked in our genes, which the team named “RetroMyelin.”
To test their discovery, the researchers conducted experiments in which they knocked out the RetroMyelin sequence in rat cells and found that they no longer produced an essential protein needed for myelin formation.
Faster reactions, bigger bodies
They then looked for RetroMyelin-like sequences in the genomes of other species, finding similar code in jawed vertebrates—mammals, birds, fish, reptiles, and amphibians—but not in jawless vertebrates or invertebrates.
This led them to believe that the sequence appeared in the tree of life around the same time as jaws, which first evolved about 360 million years ago in the Devonian period called the Age of Fishes.
“There has always been an evolutionary pressure to make nerve fibers conduct electrical impulses faster,” Franklin said. “If they do it faster, then you can act faster,” he added, which is useful for both predators trying to catch things and prey trying to escape.
Myelin allows impulses to be conducted quickly without expanding the diameter of the nerve cells, allowing them to be packed closer together.
It also provides structural support, meaning nerves can grow longer, allowing for longer limbs.
In the absence of myelin, invertebrates have found other ways to transmit signals more quickly—for example, giant squid have evolved wider nerve cells.
Finally, the team wanted to learn whether the retroviral infection happened once, in one ancestral species, or if it happened more than once.
They used computational methods to analyze the RetroMyelin sequences of 22 jawed vertebrate species, finding that the sequences were more similar within than between species, suggesting multiple waves of infection.
Are more discoveries expected?
“One tends to think of viruses as pathogens or disease-causing agents,” Franklin said.
But the reality is more complicated, he said: At various points in history, retroviruses have entered genomes and integrated into the reproductive cells of species, allowing them to be passed on to future generations.
One of the best-known examples is the placenta — one of the defining characteristics of most mammals — which we acquired from a pathogen embedded in our genome in the deep past — and there are likely many more discoveries waiting to be made, Ghosh said.
Brad Zuccero, a neuroscientist at Stanford University who was not associated with the study, said it “fills in a major piece of the puzzle of how myelin arose during evolution,” calling the paper “exciting and insightful.”
