title: Molecular evolution of myelin basic protein, an abundant structural myelin component.
abstract: Rapid nerve conduction in jawed vertebrates is facilitated by the myelination of axons, which evolved in ancient cartilaginous fish. We aim to understand the coevolution of myelin and the major myelin proteins. We found that myelin basic protein (MBP) derived from living cartilaginous fish (sharks and rays) associated with the plasma membrane of glial cells similar to the phosphatidylinositol (4,5)-bisphosphate (PIP₂)-binding marker PH-PLCδ1, and that ionomycin-induced PIP₂-hydrolysis led to its cellular redistribution. We identified two paralogous mbp genes in multiple teleost species, consistent with a genome duplication at the root of the teleost clade. Zebrafish mbpb is organized in a complex transcription unit together with the unrelated gene-of-the-oligodendrocyte-lineage (golli) while mbpa does not encode GOLLI. Moreover, the embryonic expression of mbpa and mbpb differed, indicating functional specialization after duplication. However, both mbpa and mbpb-mRNAs were detected in mature oligodendrocytes and Schwann cells, MBPa and MBPb were mass spectrometrically identified in zebrafish myelin, both associated with the plasma membrane via PIP₂, and the ratio of nonsynonymous to synonymous nucleotide-substitution rates (Ka/Ks) was low. Together, this indicates selective pressure to conserve many aspects of the cellular expression and function of MBP across vertebrate species. We propose that the PIP₂-binding function of MBP is evolutionarily old and that its emergence in ancient gnathostomata provided glial cells with the competence to myelinate.
authors.affiliation: Max Planck Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Schanila
authors.initials: S
authors.lastname: Nawaz
authors.forename: Jörn
authors.initials: J
authors.lastname: Schweitzer
authors.forename: Olaf
authors.initials: O
authors.lastname: Jahn
authors.forename: Hauke B
authors.initials: HB
authors.lastname: Werner
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D019143:Evolution, Molecular; D051379:Mice; D004676:Myelin Basic Protein / Q000138:chemical synthesis* / Q000235:genetics / Q000378:metabolism; D009186:Myelin Sheath / Q000235:genetics / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D011485:Protein Binding / Q000502:physiology; D012754:Sharks; D012860:Skates, Fish; D015027:Zebrafish
chemical_list: D004676:Myelin Basic Protein; D019269:Phosphatidylinositol 4,5-Diphosphate