Sequence variation in the primate dopamine transporter gene and its relationship to social dominance.
Sequence variation in the primate dopamine transporter gene and its relationship to social dominance.
复制标题
灵长类多巴胺转运蛋白基因的序列变异及其与社会优势的关系。
DOI：
10.1093/molbev/msm219
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发表时间：
2008
影响因子：
10.7
通讯作者：
Ferrell,RobertE
中科院分区：
文献类型：
--
作者：
Miller-Butterworth,CassandraM;Kaplan,JayR;Shaffer,John;Devlin,Bernie;Manuck,StephenB;Ferrell,RobertE
多巴胺能活动在社会主导和从属猴子之间存在差异，在人类中，它与外向性显着相关，这是一种类似于猴子社会主导的特征。此外，脑脊液中单胺代谢物的浓度具有高度遗传性。多巴胺能活性由多巴胺转运蛋白（DAT）调节，因此编码这种转运蛋白的基因是旨在鉴定功能或进化意义变体的研究的极好候选者。然而，大多数此类研究仅集中在人类同源物及其最常见的多态性，即3′非翻译区的功能可变数目串联重复序列。跨物种的比较提供了有价值的见解基因组进化，物种形成和选择机制，并可能突出进化意义的网站。然而，到目前为止，没有全面的研究DAT基因已经同时进行了多个灵长类动物物种。因此，我们的特点是序列变异和程度的连锁不平衡（LD）跨DAT基因的食蟹猴（Macaca fascicularis），恒河猴（Macacamulatta），和人类。我们确定了2个潜在的功能性变体，它们与食蟹猴的社会等级相关，对应于一个假定的转录因子结合位点。虽然在哺乳动物中高度保守，但DAT基因在人类和猕猴之间在序列变异和LD结构水平上存在显著差异，猴子的序列变异性高达人类的3倍，LD显著低于人类。这表明DAT基因在灵长类物种形成过程中遵循了不同的进化轨迹。
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 (Macacamulatta), 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.