title: Sequence variation in the primate dopamine transporter gene and its relationship to social dominance.
abstract: Dopaminergic activity differs between socially dominant and subordinate monkeys, and in humans, it correlates significantly with extraversion, a trait analogous to social dominance in monkeys. Furthermore, concentrations of monoamine metabolites within the cerebrospinal fluid are highly heritable. Dopaminergic activity is modulated by the dopamine transporter (DAT), and the gene encoding this transporter is therefore an excellent candidate for studies aiming to identify variants of functional or evolutionary significance. However, the majority of such research has focused exclusively on the human homologue and its most common polymorphism, a functional variable number tandem repeat in the 3' untranslated region. Cross-species comparisons provide valuable insights into genome evolution, speciation, and selection mechanisms and may highlight sites of evolutionary significance. To date, however, no comprehensive studies of the DAT gene have been performed simultaneously on multiple primate species. We therefore characterized sequence variation and extent of linkage disequilibrium (LD) across the DAT genes of cynomolgus macaques (Macaca fascicularis), rhesus macaques (Macaca mulatta), and humans. We identified 2 potentially functional variants, which are associated with social rank in cynomolgus monkeys and which correspond to a putative transcription factor-binding site. Although highly conserved across mammals, the DAT gene differs significantly between humans and macaques in levels of sequence variation and LD structure, with the monkeys displaying up to 3 times more sequence variability and significantly less LD than humans. This suggests that the DAT gene has followed different evolutionary trajectories during primate speciation.
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, USA. cbutterworth@hgen.pitt.edu
authors.forename: Cassandra M
authors.initials: CM
authors.lastname: Miller-Butterworth
authors.forename: Jay R
authors.initials: JR
authors.lastname: Kaplan
authors.forename: John
authors.initials: J
authors.lastname: Shaffer
authors.forename: Bernie
authors.initials: B
authors.lastname: Devlin
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Manuck
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ferrell
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001522:Behavior, Animal / Q000502:physiology*; D005075:Biological Evolution; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D014644:Genetic Variation / Q000502:physiology*; D006801:Humans; D015810:Linkage Disequilibrium / Q000502:physiology*; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D013045:Species Specificity
chemical_list: D020413:3' Untranslated Regions; D050483:Dopamine Plasma Membrane Transport Proteins