Similar Gene Coding Sequences of Neurotransmitters

Joh, Tong

Abstract

We propose that the catecholamine synthesizing enzymes, tyrosine hydroxylase (TH), dopamine-B-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT), share common gene coding sequence(s). Conceivably, these enzymes are coded for genes that have evolved through duplication of a common ancestral precusor. Further, we propose to include in our hypothesis that tryptophan hydroxylase (TPH), which catalyses the first step in serotonin biosynthesis, is also coded for by a similar gene. Evidence for the evolution of the catecholamine and serotonin synthesizing enzyme genes through mutation or duplication of ancestral gene(s) can be gained by determining their molecular anatomy. In order to prove our hypothesis, we plan the following experiments: (1) Purification of TH, DBH, PNMT and TPH to homogeneity; (2) Production of specific antibodies to each enzyme; (3) Identification of amino acid sequence homology of each enzyme, by determining amino acid compostions and sequences of peptides obtained from each enzyme by chemical and proteolytic digestion; (4) Cloning of cDNA to TH, DBH, PNMT and TPH poly(A)mRNA; and (5) Examination of the organization and structure of the genes involved in catecholamine and serotonin biosynthesis. Determination of the structural relationships between the catecholamine and serotonin synthesizing enzyme genes will contribute to elucidation of the molecular mechanisms involved in the formation of common gene coding sequence(s), and will provide valuable insight into both developmental and evolutionary processes by which neurons express the dopaminergic, noradrenergic, adrenergic or serotonergic phenotype.