The evolutionary appearance of myelin (the lipid rich sheath surrounding axons) in vertebrate bestowed a spectrum of selective advantages: it facilitates accelerated nerve impulse propagation allowing complex brain structures and enhanced morphological diversity. Our research has unveiled a critical link between myelination and the RNA level expression of RNLTR12-int, a retrotransposon of retroviral origin, demonstrating its indispensable role in this process. We have identified a mechanism whereby SOX10 binding to this RNA regulates transcription of myelin basic protein (Mbp, the major constituent of myelin) in rodents. Furthermore, global analysis of gene expression revealed that inhibition of RNLTR12-int specifically perturbed myelination network.

The temporal coincidence of myelin emergence with vertebrate jaw development is striking; jawless vertebrates notably lack both Mbp and compacted myelin. We identified RNLTR12- int like sequences (which we termed RetoMyelin) in all jawed vertebrates and demonstrated their functions in two disparate vertebrate classes (fish and frogs). Our study suggests that the acquisition of these sequences in species likely occurred through convergent evolution and co-opted for myelination function, positing retroviral endogenization is a seminal event in the origin of myelin.