Evolution of myelin proteolipid proteins: Gene duplication in teleosts and expression pattern divergence

The coevolution of neurons and their supporting glia to the highly specialized axon-myelin unit included the recruitment of proteolipids as neuronal glycoproteins (DMβ, DMγ) or myelin proteins (DMα/PLP/DM20). Consistent with a genome duplication at the root of teleosts, we identified three proteolipid pairs in zebrafish, termed DMα1 and DMα2, DMβ1 and DMβ2, DMγ1 and DMγ2. The paralogous amino acid sequences diverged remarkably after gene duplication, indicating functional specialization. Each proteolipid has adopted a distinct spatio-temporal expression pattern in neural progenitors, neurons, and in glia. DMα2, the closest homolog to mammalian PLP/DM20, is coexpressed with P0 in oligodendrocytes and upregulated after optic nerve lesion. DMγ2 is expressed in multipotential stem cells, and the other four proteolipids are confined to subsets of CNS neurons. Comparing protein sequences and gene structures from birds, teleosts, one urochordate species, and four invertebrates, we have reconstructed major steps in the evolution of proteolipids.