MBE Advance Access published online on October 13, 2007
Molecular Biology and Evolution, doi:10.1093/molbev/msm219
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Research Article |
Sequence Variation in the Primate Dopamine Transporter Gene and its Relationship to Social Dominance
1 Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, A300 Crabtree Hall, 130 De Soto Street, Pittsburgh, PA 15261, USA
2 Department of Pathology, Section of Comparative Medicine, Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC, 27157, USA
3 Computational Genetics Laboratory, Department of Psychiatry, University of Pittsburgh School of Medicine, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA
4 Behavioral Physiology Laboratory, Department of Psychology, University of Pittsburgh, 506 OEH, 4015 O'Hara St, Pittsburgh, PA, 15260, USA
Cassandra M. Miller-Butterworth, Dept of Human Genetics, GSPH, U. of Pittsburgh, A300 Crabtree Hall, Pittsburgh, PA 15261, Tel: 412-624-5392, Fax: 412-624-3020, Email: cbutterworth{at}hgen.pitt.edu
Received for publication June 22, 2007. Revision received September 28, 2007. Revision received October 2, 2007. Accepted for publication October 2, 2007.
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 (M. mulatta) and humans. We identified two 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 three times more sequence variability and significantly less LD than humans. This suggests that the dopamine transporter gene has followed different evolutionary trajectories during primate speciation.
Key Words: Macaca • dopamine transporter • linkage disequilibrium • dominance • sequence variation • primate