Ancient retroviruses played a key role in the evolution of vertebrate brains

“Retroviruses were required for vertebrate evolution,” says Robin Franklin, senior author and neuroscientist at Altus Labs-Cambridge Institute of Science. “If we didn’t have retroviruses sticking their sequences into the vertebrate genome, myelination wouldn’t happen, and without myelination, the whole diversity of vertebrates as we know them would never have happened.”

Myelin is a complex, fatty tissue that connects spinal nerve axons. This enables rapid impulse conduction without the need to increase the axonal diameter, which means that the nerve can be closely packed. It also provides metabolic support to nerves, which means nerves can lengthen. Myelin first appeared in the tree of life at the same time as jaws, and its importance in vertebrate evolution has long been recognized, but until now, it was unclear what molecular mechanisms led to its appearance. Activated the shape.

The researchers observed RetroMyelinHis role in myelin production came when he was examining the gene networks used by oligodendrocytes, the cells that produce myelin in the central nervous system. In particular, the team was investigating the role of non-coding regions, including retrotransposons, in these gene networks – something that had not previously been explored in the context of myelin biology.

“Retrotransposons make up about 40 percent of our genomes, but little is known about how they allowed animals to acquire specific traits during evolution,” says first author Tanay Ghosh, a computational biologist at Altos Labs-Cambridge Institute of Science. How can I help?” “Our motivation was to learn how these molecules are supporting evolutionary processes, particularly in the context of myelination.”

In mice, researchers found that RNA replication RetroMyelin Regulates the expression of myelin basic protein, one of the main components of myelin. When they stopped experimentally. RetroMyelin In oligodendrocytes and oligodendrocyte progenitor cells (the stem cells from which oligodendrocytes are derived), the cells can no longer produce myelin basic protein.

To check whether RetroMyelin Present in other vertebrate species, the team looked for similar sequences within the genomes of jawed vertebrates, jawless vertebrates, and several invertebrate species. They identified similar sequences in all other classes of jawed vertebrates (birds, fish, reptiles, and amphibians) but did not find similar sequences in jawed vertebrates or invertebrates.

“There’s an evolutionary drive to speed up the impulse transmission of our axons because faster impulses mean you can grab things or run away from things faster,” Franklin says.

Next, the researchers wanted to know whether RetroMyelin The ancestors of all jawed vertebrates were included once or had separate retroviral invasions in different branches. To answer these questions, they constructed a phylogenetic tree from 22 jawed vertebrate species and compared them. RetroMyelin This was revealed by continuity analysis RetroMyelin Sequences were more similar between species, suggesting that RetroMyelin was achieved multiple times through a process of convergent evolution.

The team also showed that RetroMyelin Plays an active role in myelination in fish and amphibians. When they experimentally disrupted RetroMyelin By sequencing genes in fertilized eggs of zebrafish and frogs, they found that the developing fish and tadpoles produced significantly less myelin than normal.

The study highlights the importance of non-coding regions of the genome for physiology and evolution, the researchers say. “Our findings open a new avenue of research to explore how retroviruses are generally involved in directing evolution,” says Ghosh.