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    • The androgen receptor gene AR is

    2023-05-17

    The androgen receptor gene (AR) is located on the X-chromosome and consists of eight exons in humans (Brown et al., 1989; Kuiper et al., 1989). The similar gene structure in mice, monotremes and marsupials indicates AR is highly conserved in mammals (Choong et al., 1998; Faber et al., 1991; He et al., 1990; Migeon et al., 1981; Spencer et al., 1991). The N-terminal domain of AR is coded in SW033291 1 and relates to transcription regulation by AR. Other exons code DNA binding domain and ligand binding domains (Fig. 1) (Li and Al-Azzawi, 2009; Quigley et al., 1995). In exon 1, there are trinucleotide microsatellite repeat regions, (CAG)n and (GGN)n. These repeat regions yield poly glutamine (poly-Q) and poly glycine (poly-G) repeats in the N-terminal domain. The poly-Q region is further segmented into QI and QII regions (Fig. 1). Significant variation in the length of poly-QI is known in humans. Normal repeat lengths of QI range approximately from 10 to 37 and the most frequent repeat length is 23 (Hsing et al., 2000; Huhtaniemi et al., 2009). Shorter repeats of poly-QI increase the risk of prostate cancer and extremely long repeats (>40) are related to spinal and bulbar muscular atrophy and a variable degree of androgen insensitivity although causation is controversial among studies (Rajender et al., 2007). The length polymorphism of poly-G region is also found in humans (ranges approximately from 14 to 27 repeats), while no great variation was reported for poly-QII. The length polymorphisms in these regions are also found in non-human primates. Interestingly, if a species is phylogenetically closer to humans, it possesses longer repeats and higher polymorphism comparable to humans (Choong et al., 1998; Hong et al., 2006; Mubiru et al., 2012). For example, our closest relative, the chimpanzee, has length polymorphism ranging from 15 to 27 at poly-QI but no polymorphism was found in rhesus macaques (Hong et al., 2006; Mubiru et al., 2012). The tendency of allele combination between longer poly-QI and shorter poly-G repeats in chimpanzees (Hong et al., 2006) and insusceptibility to idiopathic infertility in haplotypes with longer poly-QI and shorter poly-G combination in humans (Ferlin et al., 2004) indicates the underlying constraints on the combination of these regions. The association between these polymorphisms and personality traits such as aggressiveness has also been an intriguing topic of personality research on non-human animals as well as humans (Jonsson et al., 2001; Konno et al., 2011; Rubinow and Schmidt, 1996). Little is known, however, about the characteristics of these regions in other primates. Only one species of New World monkeys (platyrrhine), the marmoset, and several species of prosimians have been surveyed so far and no polymorphism has been found in these taxa (Mubiru et al., 2012; Poux et al., 2005). Hormonal studies have reported that the androgen concentration in several species of New World monkeys is higher than that in Old World monkeys (Snipes et al., 1969), and their androgen concentration is associated with social status (Bales et al., 2006; Schoof and Jack, 2013). These findings indicate that androgen plays an important role in behavior of New World monkeys and highlights the importance of understanding the structure and variation of AR in this taxon. Therefore, we aimed to characterize the AR gene in New World monkeys and to understand the entire picture of AR variation in primates by focusing on length polymorphism of AR poly-Q and poly-G regions and codon usage bias in 17 species of New World monkeys.
    Materials and methods
    Results
    Discussion We found polymorphisms in three species and observed that the poly-Q region is short in New Word monkeys. We also found unique codon bias in this taxon. Although great variation of CAG and GGN repeat length in the androgen receptor gene has been reported in many primate species, little was known about the variation in New World monkeys except for common marmosets (synonym: white-tufted-ear marmoset) (Mubiru et al., 2012). In this study, we surveyed 17 species of New World monkeys and found length polymorphisms at these regions in three species (squirrel monkeys, capuchin monkeys, and owl monkeys). Frequencies of each allele and the expected and the observed heterozygosity indicate the existence of large diversity in these polymorphisms. Since the sample size of common squirrel monkey and owl monkey is small, and some individuals are related to each other in capuchins and squirrel monkeys, caution should be taken regarding the interpretation of the extent of diversity. We did not observe polymorphism either in Q repeat nor G repeat regions in Callitrichidae, tamarins and marmosets. This observation is consistent with a previous report that showed no length polymorphism in common marmosets (Mubiru et al., 2012). For species that possess polymorphisms, it would be interesting to examine if there are functional differences among alleles.