Molecular evolution of myelin basic protein, an abundant structural myelin component

Area of Science:

• Neuroscience
• Evolutionary Biology
• Molecular Biology

Background:

• Myelination of axons is crucial for rapid nerve conduction in jawed vertebrates.
• Myelination evolved in ancient cartilaginous fish, necessitating an understanding of myelin protein evolution.

Purpose of the Study:

• To investigate the coevolution of myelin and major myelin proteins, specifically myelin basic protein (MBP).
• To determine the evolutionary origins and conserved functions of MBP, particularly its interaction with cell membranes.

Main Methods:

• Analysis of MBP from cartilaginous fish for plasma membrane association using PIP₂ markers.
• Identification and characterization of MBP genes (mbp) in teleost fish, including gene duplication events.
• Examination of embryonic and mature expression patterns of zebrafish mbpa and mbpb.
• Mass spectrometry to identify MBP in zebrafish myelin.
• Calculation of Ka/Ks ratios to assess selective pressure on MBP genes.

Main Results:

• Cartilaginous fish MBP associates with glial cell membranes via PIP₂, with redistribution upon PIP₂ hydrolysis.
• Teleost fish possess two paralogous MBP genes (mbpa and mbpb) resulting from genome duplication.
• Zebrafish mbpa and mbpb show distinct embryonic expression but are both found in mature myelinating cells (oligodendrocytes and Schwann cells).
• Both MBPa and MBPb were identified in zebrafish myelin and associate with the plasma membrane via PIP₂.
• Low Ka/Ks ratios indicate strong evolutionary conservation of MBP.

Conclusions:

• The PIP₂-binding function of MBP is an ancient trait, present in early jawed vertebrates.
• This conserved PIP₂-binding mechanism likely provided glial cells with the fundamental ability to myelinate.
• MBP evolution demonstrates significant selective pressure to maintain its cellular expression and membrane-binding function across vertebrate species.