Molecular biology of catecholamine neurons. Similar gene hypothesis.

We have postulated that the catecholamine-synthesizing enzymes tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), and phenylethanolamine N-methyltransferase (PNMT) are coded for by similar genes. To analyze the structural relationship of genes coding for these enzymes, we have cloned DNAs complementary (cDNA) to DBH and PNMT messenger RNAs (mRNAs). Using hybrid selection analysis to identify the cDNA clones positively, we discovered cross-hybridization between DBH cDNA clones and PNMT mRNA and between PNMT cDNA clones and DBH mRNA. Further analysis by RNA blot hybridization revealed that the DBH cDNA probe hybridized predominantly to a 5500 nucleotide mRNA and less strongly to a 1100 nucleotide species, and the PNMT cDNA probe hybridized strongly to the 1100 nucleotide mRNA and weakly to the 5500 nucleotide message. DNA blot hybridization analysis demonstrated that DBH and PNMT cDNA probes hybridized to several common restriction fragments of total cellular DNA. The evidence presented here suggests the existence of homologous gene-coding regions in DBH and PNMT cDNAs. These homologies may be the result of duplication of a common ancestral gene. DNA blot analysis suggests that these enzymes are coded for by single genes, which may be located in close proximity to each other in the DNA, and points to the existence of either a single gene or linked genes coding for all catecholamine enzymes.