The evolution of vertebrate neural isozymes

A striking correlation between neural expression and high net negative charge in some teleost isozymes led to the, as yet untested, suggestion that negative charge represents an adaptation to the neural environment.; Two TPI proteins, a generally expressed, neutrally charged, isozyme and a neurally expressed, negatively charged, isozyme, are present in teleost fishes. A single, generally expressed, TPI isozymes is present in more primitive fish. A TPI gene phylogeny identifies a single gene duplication event early in the evolution of bony fishes. Comparisons between inferred ancestral TPI sequences indicate that the neural TPI isozyme evolved through a period of directional selection accumulating negatively charged amino acids.; Negative neural isozymes are not limited to teleost fish, but are present across vertebrate taxa. The literature contains examples of negatively charged neural isozymes common to both tetrapod and teleost vertebrates, but no meaningfully comparison of these isozymes has been made between these groups. ALD-C is a negatively charged neural isozyme present in both tetrapod and teleost vertebrates. While these ALD-C isozymes are products of orthologous genes, the negative charge of the ALD-C isozymes in each group is largely the product of distinct sets of negative amino acids. This could result from either convergent evolution to a similar phenotype (negative charge), or divergent evolution from a negatively charged common ancestor.; The MDH gene family is an exception to the general correlation of neural expression and strong negative charge. Teleost fishes express two MDH isozymes: one neurally expressed and the other expressed in all tissues. I demonstrate that the two teleost MDH isozymes result from a gene duplication early in the radiation of teleost fishes and that directly following this duplication the neural MDH evolved through a period of positive selection. While the neural MDH isozyme is slightly more negatively charged than the generally expressed isozyme, the differential in charge is not as pronounced as observed in other gene families. Perhaps because of this, the pattern of amino acid substitution directly following the gene duplication does not differ from that across the rest of the MDH gene tree.