Parallel Evolution and Coexpression of the Proteolipid Proteins and Protein Zero in Vertebrate Myelin

Vertebrate myelin contains two proteins that mediate compaction: protein zero (P0), an immunoglobulin gene superfamily member, or proteolipid proteins, 4-hydrophobic domain-motif proteins biogenetically unrelated to P0. The prevailing view has been that expression of P0 and proteolipid proteins is mutually exclusive; P0, which mediates myelin compaction in fish, is thought to be completely replaced by the newer proteolipid proteins in the terrestrial vertebrate CNS. However, we now find that proteolipid proteins are actually major myelin constituents in bony fish and amphibia, and so are coexpressed with P0. Clearly, myelin proteolipids are not new additions to the myelin protein repertoire, but instead were ancestral sheath components, expressed approximately 440 million years ago in the first myelinated fish that existed at least approximately 100 million years before the origin of amphibians. In conclusion, P0 and the proteolipid proteins are evolving in parallel in myelinating cells of most vertebrate species.