The researchers report February 15 in the journal. Cell that ancient viruses may be responsible for myelin and, by extension, our large, complex brains. The team discovered that a retrovirus-derived genetic element or “retrotransposon” is essential for myelin production in mammals, amphibians and fish. The sequence of the gene, which they called “Retromyelin,” is probably the result of an ancient viral infection, and comparisons of Retromyelin in mammals, amphibians, and fish suggest that retroviral infection and genome invasion events occurred separately in each of these groups.
“Retroviruses were necessary to get vertebrate evolution off the ground,” says lead author and neuroscientist Robin Franklin of Altos Labs-Cambridge Institute of Science. “If we didn't have retroviruses pasting their sequences into the vertebrate genome, then myelination would not have occurred, and without myelination, all vertebrate diversity as we know it would never have happened.”
Myelin is a complex fatty tissue that surrounds the nerve axons of vertebrates. It allows rapid conduction of impulses without the need to increase axonal diameter, meaning nerves can be packed closer together. It also provides metabolic support to the nerves, meaning the nerves can last longer. Myelin first appeared in the tree of life around the same time as jaws, and its importance in vertebrate evolution has long been recognized, but until now it was unclear what molecular mechanisms triggered its appearance.
The researchers noticed RetromyelinThe role of in myelin production when they examined the genetic networks used by oligodendrocytes, the cells that produce myelin in the central nervous system. Specifically, the team was investigating the role of non-coding regions, including retrotransposons, in these genetic networks, something that had not been previously explored in the context of myelin biology.
“Retrotransposons make up about 40% of our genomes, but nothing is known about how they might have helped animals acquire specific characteristics during evolution,” says first author Tanay Ghosh, a computational biologist at Altos Labs-Cambridge Institute of Technology. Science. “Our motivation was to know how these molecules are helping evolutionary processes, specifically in the context of myelination.”
In rodents, the researchers found that RNA transcription of Retromyelin regulates the expression of myelin basic protein, one of the key components of myelin. When they experimentally inhibited Retromyelin In oligodendrocytes and oligodendrocyte progenitor cells (the stem cells from which oligodendrocytes are derived), the cells could no longer produce myelin basic protein.
To examine whether Retromyelin is present in other vertebrate species, the team looked for similar sequences in the genomes of jawed vertebrates, jawless vertebrates, and several invertebrate species. They identified analogous sequences in all other classes of jawed vertebrates (birds, fish, reptiles, and amphibians), but did not find a similar sequence in jawless vertebrates or invertebrates.
“There has been an evolutionary push to make the impulse conduction of our axons faster because having faster impulse conduction means you can catch things or run away from them more quickly,” Franklin says.
Next, the researchers wanted to know if Retromyelin was incorporated once in the ancestor of all jawed vertebrates or whether there were separate retroviral invasions in different branches. To answer these questions, they constructed a phylogenetic tree from 22 species of jawed vertebrates and compared their Retromyelin sequences. The analysis revealed that Retromyelin The sequences were more similar within species than between them, suggesting that Retromyelin It was acquired several times through the process of convergent evolution.
The team also showed that Retromyelin It plays a functional role in myelination in fish and amphibians. When they experimentally altered the Retromyelin genetic sequence in the fertilized eggs of zebrafish and frogs, they found that the developing fish and tadpoles produced significantly less myelin than usual.
The researchers say the study highlights the importance of non-coding regions of the genome for physiology and evolution. “Our findings open a new avenue of research to explore how retroviruses more generally participate in directing evolution,” says Ghosh.