EVOLUTION OF NEUROTRANSMITTER SYNTHETIC ENZYME GENES AND THE PATTERNING OF SEROTONERGIC NEURONS IN CAENORHABDITIS AND OTHER NEMATODES
C. M. Loer
Dept Biology, Univ San Diego, San Diego, CA, USA
The biogenic amine neurotransmitters serotonin and dopamine are synthesized via two enzymatic steps by an aromatic amino acid hydroxylase (AAH) and aromatic amino acid decarboxylase (AADC). The AADC enzyme, which has a broad substrate specificity, is shared by both synthetic pathways in all animals, including the vertebrates, insects and nematodes. AADC belongs to a larger family of pyridoxal phosphate-dependent decarboxylases (PLP-DC) that includes histidine DC (histamine sythesis), tyrosine DC (octopamine synthesis in animals, alkaloid synthesis in plants) and the more distantly related glutamate decarboxylase (GABA synthesis). We have previously identified the serotonin- and dopamine synthetic AADC in the nematode C. elegans as encoded by the bas-1 gene. The C. elegans genome encodes five additional PLP-DC genes, some of which have no obvious homolog in other animals. In addition, two close relatives of bas-1 found in C. elegans (C05D2.3, F12A10.3) are missing from the C. briggsae genome. Phylogenetic analysis reveals that the bas-1-like genes (or a common ancestor) were originally present in the C. briggsae lineage, but were lost. In C. elegans, the bas-1-like gene F12A10.3 appears to be an expressed pseudogene. C05D2.3, which is just downstream of bas-1 (aka C05D2.4), encodes a protein lacking amino acids critical to the function of an AADC. Comparing ratios of non-synonymous to synonymous substitutions (KAKS) suggests that the bas-1-like genes are under relaxed selection, unlike the bas-1 and other AADC genes, which are under strong purifying selection. Ongoing sequencing of other Caenorhabditis genomes should provide additional insight into questions about the evolutionary fates of duplicate genes such as these.
We have also recently begun an examination of the patterning and function of serotonergic neurons in free-living nematode relatives of C. elegans. We have found considerable variability in the numbers and patterns of serotonergic neurons, especially those regulating reproductive behaviors. Supported by NIH R15-GM60203.