The Serotonin Transporter: Sequence Variation in Macaca fascicularis and its Relationship to Dominance

Abstract

Specific genotypes of the rhesus monkey and human serotonin transporter gene (SERT) promoter region are associated with personality traits and serotonergic activity. However, the most commonly studied promoter polymorphism (5-HTTLPR) is monomorphic in many other monkey species. To date, no systematic search for alternative potentially functional polymorphisms across the remaining coding parts of the gene has been undertaken in other primate species, despite the crucial role SERT plays in modulating serotonergic tone. We investigated whether sequence variation in this gene is associated with social rank and serotonin metabolite (5-HIAA) differences in 524 cynomolgus macaques. Sequence variation and extent of linkage disequilibrium (LD) across the regulatory and coding regions were initially characterized in 92 macaques. The exons and promoter contained 28 polymorphisms, more than double that recorded for human SERT. In further contrast to humans, the macaque SERT showed no significant LD. Potentially functional polymorphisms were genotyped in all animals. No individual variants or haplotypes were significantly associated with social rank or 5-HIAA concentrations; however, certain serotonin transporter diplotypes may modulate acquisition of dominance status.

Cognitive impact of genetic variation of the serotonin transporter in primates is associated with differences in brain morphology rather than serotonin neurotransmission

“…Four animals were homozygous for the Long variant (LL) of a polymorphic repetitive element in the promoter region of the serotonin transporter (SERT) and 4 animals had a LS (Long-Short variant) genotype. The genotyping of the subjects was conducted as previously described (28). Animals were experienced in working on a touch screen in a sound-attenuated chamber for water rewards and trained on specific stimuli and task-specific criteria prior to each task (for a detailed description of the behavioral tasks, see Supplement).…”

Genetic Influences on Behavior in Nonhuman Primates

“…In the 5′UTR promoter region of SLC6A3 (the gene that encodes the DAT protein), two single nucleotide polymorphisms (SNPs) associated with transcription factor binding sites have been associated with social rank in cynomolgus macaques (Miller-Butterworth et al 2007). One of those SNPs was also found in rhesus macaques, and is also associated with social dominance behaviors.…”

“…Dominant individuals tend to be more aggressive, initiate agonistic encounters, display attack gestures and vocalizations, and consistently defeat lower ranking conspecifics. Subordinates display gestures and vocalizations associated with submission and flight, and tended to flee or cower when placed in agonist encounters with a dominant individual (Miller-Butterworth et al 2007). While many factors can influence social dominance hierarchies such as personality, earlylife history, physiological traits such as size, and the immediate social environment, both male and female macaques tended to retain the same relative dominance status even when assigned to different social groups (reviewed in Miller- Butterworth et al 2008).…”

Interspecies and intraspecies variations in the serotonin transporter gene intron 3 VNTR in nonhuman primates

“…In the Old World monkeys, no variation was observed in the repeat numbers of the Japanese macaques (Macaca fuscata) and patas monkeys (Erythrocebus patas) examined; only a 5-repeat allele was recognized in these monkeys and in the previously reported macaque (M. fascicularis) and baboons (Papio papio and P. hamadryas) (Soeby et al 2005;Miller-Butterworth et al 2007).…”