Structural variation of the monoamine oxidase A gene promoter repeat polymorphism in nonhuman primates

Abstract

By conferring allele-specific transcriptional activity on the monoamine oxidase A (MAOA) gene in humans, length variation of a repetitive sequence [(variable number of tandem repeat (VNTR)] in the MAOA promoter influences a constellation of personality traits related to aggressive and antisocial behavior and increases the risk of neurodevelopmental and psychiatric disorders. Here, we have analyzed the presence and variability of this MAOA promoter repeat in several species of nonhuman primates. Sequence analysis of MAOA's transcriptional control region revealed the presence of the VNTR in chimpanzee (Pan troglodytes), bonobo (Pan paniscus), gorilla (Gorilla gorilla), orangutan (Pongo pygmaeus), rhesus macaque (Macaca mulatta) and Gelada baboon (Theropithecus gelada). The majority of P. troglodytes and P. paniscus showed a single repeat with a sequence identical to the VNTR sequence in humans. In contrast, analyses of the remaining species revealed shorter sequences similar to the first 18 bp of human VNTR. Compared with other nonhuman primates, the VNTR sequence of M. mulatta showed the highest length variability with allele frequencies of 35, 25 and 40% for the five, six and seven repeat variants, respectively. The extent of variability of the MAOA promoter repeat in both rhesus monkeys and humans supports the notion that there may be a relationship between functional MAOA expression and aggression-related traits in humans and rhesus macaque populations.

Nature and Nurture Predispose to Violent Behavior: Serotonergic Genes and Adverse Childhood Environment

“…A further study failed to replicate the Dunedin findings, although there was a nonsignificant trend (Haberstick et al, 2005). Analogous to humans, rhesus monkeysFwhich feature a polymorphic VNTR in their MAOA regulatory region as well (Wendland et al, 2006)Fshow higher aggression levels in the presence of low-activity alleles, however, this was significant only when monkeys were mother-and not peer-reared .…”

The role of monoamine oxidase A in aggression: Current translational developments and future challenges

“…Most of the preclinical studies on the role of MAOA genotypic variants have been produced in non-human primates (Barr and Driscoll, 2014). Sequence analysis studies have revealed the presence of functional VNTRs in the transcriptional control region of MAOA across several species of monkeys (such as Rhesus macaques and Gelada baboon) as well as apes (including gorillas, orangutans, chimpanzees and bonobos) (Wendland et al, 2006). In particular, the alleles in the rh MAOA -LPR (an upstream functional polymorphism regulating MAOA transcription) in Rhesus monkeys show a great degree of variability, particularly in societies with high levels of intermale conflicts for dominance, suggesting a likely homology with the uVNTR polymorphism (Wendland et al, 2006).…”

“…Sequence analysis studies have revealed the presence of functional VNTRs in the transcriptional control region of MAOA across several species of monkeys (such as Rhesus macaques and Gelada baboon) as well as apes (including gorillas, orangutans, chimpanzees and bonobos) (Wendland et al, 2006). In particular, the alleles in the rh MAOA -LPR (an upstream functional polymorphism regulating MAOA transcription) in Rhesus monkeys show a great degree of variability, particularly in societies with high levels of intermale conflicts for dominance, suggesting a likely homology with the uVNTR polymorphism (Wendland et al, 2006). These variants have also been shown to participate in GxE interactions with early rearing experiences; for instance, male macaques raised with or without their mothers were found to exhibit competitive behavior and social group aggression in a MAOA -dependent fashion.…”

Cluster B Personality Disorders are Associated with Allelic Variation of Monoamine Oxidase A Activity

“…A corresponding MAOA genotype  environment interaction effect on aggression was recently demonstrated in rhesus macaques, in which gene transcription is also modulated by an analogous polymorphic repeat in the upstream regulatory region of MAOA (rhMAOA-LPR) (Newman et al, 2004). Detailed species comparisons revealed that the MAOA-LPR is differentially configured among non-human primates but absent in other mammalians (Wendland et al, 2005).…”