Evolution of Dopamine-Related Systems: Biosynthesis, Degradation and Receptors

Abstract

The evolution of enzyme genes at the pathway level has attracted increasing attention in recent years. Most investigations have focused on microorganisms, plants and invertebrates but rarely on vertebrates. The dopamine pathway, which participates in almost every aspect of brain function, is an excellent candidate for study at the pathway level. Herein, we report data on the divergence of six dopamine metabolic enzyme genes (three anabolic, three catabolic enzymes) and five dopamine receptor genes across five mammals, namely Homo sapiens, Pan troglodytes, Macaca mulatta, Mus musculus, and Rattus norvegicus. For enzyme genes, our data confirm previous conclusion that the upstream genes have evolved more slowly than downstream genes. Moreover, we found that catabolic genes in the dopamine metabolic pathway have evolved faster than anabolic genes, and maximum likelihood analysis suggested that this difference in evolutionary rate may be explained by anabolic genes being more constrained during selection. For dopamine receptor genes, however, the broadly expressed genes have tended to evolve more slowly than the narrowly expressed genes; maximum likelihood analysis showed that the relatively rapid evolutionary rate of the narrowly expressed receptor genes was a consequence of relaxed selective constraints. Finally, our data imply that selective constraints on synonymous sites in enzyme genes are relaxed compared with those of receptor genes because of differences in their patterns of functional regulation.