Scientists have uncovered a fascinating link between ancient viruses and the development of myelination, the biological process crucial for the advanced functioning of the nervous system in vertebrates, including humans. This discovery sheds light on the evolutionary puzzle of how complex brains and sophisticated nervous systems evolved in animals.
The researchers have identified a genetic element, named “RetroMyelin,” derived from retroviruses, as essential for the production of myelin in a broad range of vertebrates, including mammals, amphibians, and fish. This finding, published in the journal Cell, suggests that the intrusion of viral sequences into the genomes of early vertebrates was a pivotal step in the evolution of myelination, thereby enabling the development of complex brains and diverse vertebrate life.
Myelination is the process by which nerve fibers are wrapped in a fatty insulating sheath called myelin. This sheath is critical for the rapid transmission of electrical signals along nerve cells, facilitating efficient communication within the nervous system. Myelin not only speeds up signal transmission but also provides metabolic support to nerve fibers, allowing them to extend over long distances without losing signal strength.
The advent of myelination was a significant evolutionary development, coinciding with the emergence of jaws in vertebrates. This evolutionary milestone enabled the compact packing of nerve fibers and the emergence of complex nervous systems, underpinning the vast diversity and adaptability of vertebrate species.
Driven by curiosity about how myelination first emerged in vertebrates, a team led by neuroscientist Robin Franklin at Altos Labs-Cambridge Institute of Science embarked on a journey to explore the molecular underpinnings of this process.
“Retroviruses were required for vertebrate evolution to take off,” Franklin explained. “If we didn’t have retroviruses sticking their sequences into the vertebrate genome, then myelination wouldn’t have happened, and without myelination, the whole diversity of vertebrates as we know it would never have happened.”
They focused on the role of retrotransposons, fragments of DNA derived from ancient viruses that have integrated into the genome of host organisms over millions of years. These genetic elements, making up a significant portion of the genome, have long been speculated to play a role in evolutionary development, yet their contribution to specific physiological traits like myelination remained unexplored until now.
“Retrotransposons compose about 40% of our genomes, but nothing is known about how they might have helped animals acquire specific characteristics during evolution,” said first author Tanay Ghosh, a computational biologist at Altos Labs-Cambridge Institute of Science. “Our motivation was to know how these molecules are helping evolutionary processes, specifically in the context of myelination.”
By analyzing gene networks in oligodendrocytes, the cells responsible for producing myelin in the central nervous system, the researchers discovered the critical role of RetroMyelin. In rodents, inhibiting RetroMyelin resulted in the failure to produce myelin basic protein, a key component of the myelin sheath.
The team extended their analysis across the animal kingdom, finding similar genetic sequences in other jawed vertebrates but not in jawless vertebrates or invertebrates. This pattern suggested a repeated evolutionary theme: the integration of RetroMyelin into the genomes of different vertebrate lineages through separate viral invasion events.
The presence of RetroMyelin in all examined jawed vertebrates and its essential role in myelination indicate that ancient viral infections were not merely random events but were instrumental in shaping the complex nervous systems of today’s vertebrates. By comparing RetroMyelin sequences across 22 species, the researchers demonstrated that these sequences were more similar within species than between them, supporting the theory of convergent evolution through separate viral invasions.
“There’s been an evolutionary drive to make impulse conduction of our axons quicker because having quicker impulse conduction means you can catch things or flee from things more rapidly,” Franklin explained.
Functional experiments in zebrafish and frogs further validated the importance of RetroMyelin in myelination, showing a significant reduction in myelin production when RetroMyelin was disrupted. This highlights the universal role of RetroMyelin in vertebrate myelination and opens new avenues for understanding the molecular mechanisms of myelin production and its evolutionary origins.
“Our findings open up a new avenue of research to explore how retroviruses are more generally involved in directing evolution,” Ghosh said.
The study, “A retroviral link to vertebrate myelination through retrotransposon-RNA-mediated control of myelin gene expression,” was authored by Tanay Ghosh, Rafael G. Almeida, Chao Zhao, Abdelkrim Mannioui, Elodie Martin, Alex Fleet, Civia Z. Chen, Peggy Assinck, Sophie Ellams, Ginez A. Gonzalez, Stephen C. Graham, David H. Rowitch, Katherine Stott, Ian Adams, Bernard Zalc, Nick Goldman, David A. Lyons, and Robin J.M. Franklin.
