Evidence for a period of directional selection following gene duplication in a neurally expressed locus of triosephosphate isomerase.

A striking correlation between neural expression and high net negative charge in some teleost isozymes led to the interesting, yet untested, suggestion that negative charge represents an adaptation (via natural selection) to the neural environment. We examine the evolution of the triosephosphate isomerase (TPI) gene family in fishes for periods of positive selection. Teleost fish express two TPI proteins, including a generally expressed, neutrally charged isozyme and a neurally expressed, negatively charged isozyme; more primitive fish express only a single, generally expressed TPI isozyme. The TPI gene phylogeny constructed from sequences isolated from two teleosts, a single acipenseriform, and other TPI sequences from the databases, supports 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 positive selection resulting in the biased accumulation of negatively charged amino acids. Further, the number of nucleotide changes required for the observed amino acid substitutions suggests that selection acted on the overall charge of the protein and not on specific key amino acids.