Phylogenetic analysis and selection pressures of 5-HT receptors in human and non-human primates: receptor of an ancient neurotransmitter.
Neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) an ancient neurotransmitter, involved in several neurophysiological and behavioral functions, acts by interacting with multiple receptors (5-HT(1)-5-HT(7)). Alterations in serotonergic signalling have also been implicated in various psychiatric disorders. The availability of the genome data of non-human primates permits comparative analysis of human 5-HT receptors with sequences of non-human primates to understand evolutionary divergence. We compared and analyzed serotonergic receptor sequences from human and non-human primates. Phylogenetic analysis by Maximum Likelihood (ML) method classified human and primate 5-HT receptors into six unique clusters. There was considerable conservation of 5-HT receptor sequences between human and non-human primates; however, a greater diversity at the sub-group level was observed. Compared to the other subgroups, larger multiplicity and expansion was seen within the 5-HT(4) receptor subtype in both human and non-human primates. Analysis of non-synonymous and synonymous substitution ratios (Ka/Ks ratio) using the Nei-Gojobori method suggests that 5-HT receptor sequences have undergone negative (purifying) selection over the course of evolution in human, chimpanzee and rhesus monkey. Abnormal human and non-human primate psychopathalogy and behavior, in the context of these variations is discussed. Analysis of these 5-HT receptors in other species will help understand the molecular evolution of 5-HT receptors, and its possible influence on complex behaviors, and psychiatric disorders.
Anbazhagan
Padmanabhan
P
Molecular Genetics Laboratory, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore-560029, India.
Purushottam
Meera
M
Kumar
H B Kiran
HB
Mukherjee
Odity
O
Jain
Sanjeev
S
Sowdhamini
Ramanathan
R
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D016000:Cluster Analysis; D019143:Evolution, Molecular; D006801:Humans; D001523:Mental Disorders / Q000235:genetics / Q000473:pathology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D016366:Open Reading Frames / Q000235:genetics; D010802:Phylogeny; D011323:Primates / Q000235:genetics*; D011985:Receptors, Serotonin / Q000235:genetics*; D012641:Selection, Genetic; D020539:Sequence Analysis, Protein; D012701:Serotonin / Q000378:metabolism*; D012919:Social Behavior
D018377:Neurotransmitter Agents; D011985:Receptors, Serotonin; D012701:Serotonin