The evolutionary divergence of neurotransmitter receptors and second-messenger pathways

Abstract

Members of the superfamily of G-protein-coupled neurotransmitter receptors have a conserved secondary structure, a moderate and reasonably steady rate of sequence change, and usually lack introns within the coding sequence. These properties are advantageous for evolutionary studies. The duplication and divergence of the genes in this gene family led to the formation of distinct neurotransmitter pathways and may have facilitated the evolution of complex nervous systems. I have analyzed this evolutionary divergence by quantitative multiple sequence alignment, bootstrap resampling, and statistical analysis of 49 adrenergic, muscarinic cholinergic, dopamine, and octopamine receptor sequences from 12 animal species. The results indicate that the first event to occur within this gene family was the divergence of the catecholamine receptors from the muscarinic acetylcholine receptors, which occurred prior to the divergence of the arthropod and vertebrate lineages. Subsequently, the ability to activate specific second-messenger pathways diverged independently in both the muscarinic and the catecholamine receptors. This appears to have occurred after the divergence of the arthropod and vertebrate lineages but before the divergence of the avian and mammalian lineages. However, the second-messenger pathways activated by adrenergic and dopamine receptors did not diverge independently. Rather, the ability of the catecholamine receptors to bind to specific ligands, such as epinephrine, norepinephrine, dopamine, or octopamine, was repeatedly modified in evolutionary history, and in some cases was modified after the divergence of the second-messenger pathways.

Evolution of the Neuropeptide Y Receptor Family: Gene and Chromosome Duplications Deduced from the Cloning and Mapping of the Five Receptor Subtype Genes in Pig

“…Another paralogous region is implicated on HSA8, along with several genes localizing to "other" chromosomes, but not forming a large cluster. The asterisk (*) indicates that we did not find a reference phylogenetic tree for this gene family; for the other gene families the following references were used: hexokinase (Cardenas et al 1998); ankyrins (Pebusque et al 1998); dopamine receptors (Fryxell 1995;Cardinaud et al 1997); annexins (Morgan et al 1998); adrenergic receptors (Fryxell 1995); BMP receptors and TGF-␤ signal transducers (Newfeld et al 1999); glycine receptors (David-Watine et al 1999); receptor tyrosine kinases (Rousset et al 1995); FGF receptors (Coulier et al 1997); EGFs (Hughes 1999 Fig. 2).…”

Characterization and functional divergence of the α1-adrenoceptor gene family: insights from rainbow trout (Oncorhynchus mykiss)

“…The sequences found are listed in Table 2. The out-group sequences are based on the dopamine D1 receptor, as first, it is the closest relative to the ␣ 1-AR in a phylogenetic study (16), and second, the dopamine receptor appeared as the best reciprocal BLAST hit of ␣ 1-ARs in lower vertebrates. Sequences were aligned with CLUSTAL W version 1.8 (35) at the amino acid level and back translated to DNA to obtain the nucleotide sequence alignments.…”

Is there an evolutionary mismatch between the normal physiology of the human dopaminergic system and current environmental conditions in industrialized countries?

“…Rather, the ability of the catecholamine receptors to bind to specific ligands, such as epinephrine, norepinephrine, dopamine, or octopamine, was repeatedly modified in evolutionary history, and in some cases was modified after the divergence of the second-messenger pathways. 19 When the distribution of the dopamine D1 and D2 receptors in the brain of a mouse, rat, or cat is compared with that of a monkey, similarities are found only in the basal ganglia; the highest density being present in the caudate-putamen, in the nucleus accumbens, in the olfactory tubercle, and in the substantia nigra. Apart from these nuclei, and particularly in more recent structures such as the cerebellum and the frontal cortex, the absolute and relative values of the dopamine receptor subtypes is completely different in primates, suggesting that the transcriptional control of the gene encoding for the dopaminergic receptors has also undergone profound changes throughout evolution.…”