In a recent study published in Cell, scientists have revealed the pivotal role of ancient viruses in the development of myelin, a critical component for the complexity of vertebrate brains. The research team, led by Robin Franklin at Altos Labs-Cambridge Institute of Science, discovered a retrovirus-derived genetic element, named "RetroMyelin," which is crucial for myelin production across mammals, amphibians, and fish. This finding suggests that the integration of viral sequences into the vertebrate genome was a significant factor in the evolution of vertebrates.
Robin Franklin elucidated the critical role of retroviruses in vertebrate evolution, stating, "Retroviruses were required for vertebrate evolution to take off. 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."
Myelin, a complex, fatty tissue surrounding nerve axons, is essential for rapid impulse conduction and metabolic support to nerves. Its evolutionary origin has been a mystery until the identification of RetroMyelin's role in its production. The discovery came while examining gene networks in oligodendrocytes, the central nervous system cells responsible for myelin production, with a particular focus on noncoding regions including retrotransposons.
Tanay Ghosh, a computational biologist, and the study's first author, emphasized the novelty of their approach, saying, "Retrotransposons compose about 40% of our genomes, but nothing is known about how they might have helped animals acquire specific characteristics during evolution. Our motivation was to know how these molecules are helping evolutionary processes, specifically in the context of myelination."
The team's research showed that in rodents, the RNA transcript of RetroMyelin regulates the expression of myelin basic protein, a crucial myelin component. Inhibition of RetroMyelin in oligodendrocytes led to a failure in producing this protein. Further investigations revealed the presence of RetroMyelin sequences across various jawed vertebrates but not in jawless vertebrates or invertebrates, pointing to a jawed vertebrate-specific evolutionary event.
Exploring the evolutionary trajectory of RetroMyelin, the researchers constructed a phylogenetic tree and found evidence suggesting multiple acquisitions of RetroMyelin through convergent evolution, rather than a single integration event in the ancestor of all jawed vertebrates.
Functional assays in zebrafish and frogs confirmed RetroMyelin's role in myelination, with disruptions leading to reduced myelin production. Franklin highlighted the evolutionary advantage conferred by myelin, stating, "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."
This study not only sheds light on the genetic and molecular underpinnings of myelination but also underscores the significant impact of retroviruses and non-coding genomic regions on vertebrate evolution. Ghosh concluded, "Our findings open up a new avenue of research to explore how retroviruses are more generally involved in directing evolution," marking a significant step forward in understanding the complex interplay between viral elements and evolutionary processes.
Original Publication
Ghosh, T., Almeida, R. G., Zhao, C., Mannioui, A., Martin, E., Fleet, A., Chen, C. Z., Assinck, P., Ellams, S., Gonzalez, G. A., Graham, S. C., Rowitch, D. H., Stott, K., Adams, I., Zalc, B., Goldman, N., Lyons, D. A., & Franklin, R. J. M. (2024). A retroviral link to vertebrate myelination through retrotransposon-RNA-mediated control of myelin gene expression. Cell, 187(4), 814–830.e23. https://doi.org/10.1016/j.cell.2024.01.011