MBE Advance Access originally published online on October 13, 2007
Molecular Biology and Evolution 2008 25(1):18-28; doi:10.1093/molbev/msm219
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Research Articles |
Sequence Variation in the Primate Dopamine Transporter Gene and Its Relationship to Social Dominance
* Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh
E-mail: cbutterworth{at}hgen.pitt.edu.
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 (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.
Key Words: Macaca • dopamine transporter • linkage disequilibrium • dominance • sequence variation • primate
1 Present address: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh.
2 Present address: Department of Pathology, Section of Comparative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC.
3 Present address: Computational Genetics Laboratory, Department of Psychiatry, University of Pittsburgh School of Medicine.
4 Present address: Behavioral Physiology Laboratory, Department of Psychology, University of Pittsburgh.