Evolution of a behavior-linked microsatellite-containing element in the 5' flanking region of the primate AVPR1A gene.
Evolution of a behavior-linked microsatellite-containing element in the 5' flanking region of the primate AVPR1A gene.
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DOI：
10.1186/1471-2148-8-180
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发表时间：
2008-06-23
影响因子：
3.4
通讯作者：
Young LJ
中科院分区：
文献类型：
--
作者：
Donaldson ZR;Kondrashov FA;Putnam A;Bai Y;Stoinski TL;Hammock EA;Young LJ
精氨酸加压素 V1a 受体 (V1aR) 调节多种物种的社会认知和行为。啮齿动物 V1aR 基因 (AVPR1A) 5' 侧翼区域重复微卫星元件的变异与大脑 V1aR 表达和社会行为的变异有关。在人类中，AVPR1A 的 5' 侧翼区域包含两个约 350 bp 的串联重复，含有微卫星的元件位于转录起始位点上游约 3.5 kb 处。第一个块称为 DupA，包含多态性 (GT)25 微卫星；第二个块 DupB 具有复杂的 (CT)4-(TT)-(CT)8-(GT)24 多态性基序，称为 RS3。 RS3 的多态性与人类社会行为特征的变异有关，包括自闭症谱系障碍。因此，这些区域的进化可能导致了灵长类动物社会行为的变化。我们检查了六种猿类、六种猴子和一种原猴物种的这些区域的结构。在我们研究的五种猿类中，这两个串联重复序列块都存在于 AVPR1A 编码区的上游，而猴子只有该区域的一个拷贝。与人类一样，DupA 和 DupB 内的微卫星在许多灵长类动物中也是多态性的。此外，根据对 47 个野生捕获个体的分析，单一等位基因（缺乏 DupB）和重复等位基因（包含 DupA 和 DupB）均存在于黑猩猩（Pan troglodytes）群体中，单一等位基因和重复等位基因的等位基因频率分别为 0.795 和 0.205。最后，系统发育重建表明该基因座有两种不同的进化历史。 RS3 重复的存在与灵长类动物的社会组织之间没有明显的关系。然而，在某些物种中发现的多态性可能对未来的遗传关联研究有用。特别是，黑猩猩中单个等位基因和重复等位基因的存在为评估这种重复在灵长类动物社会行为变异中的功能作用提供了独特的机会。虽然我们的初步研究显示黑猩猩中该位点没有定向选择的迹象，但药理学和遗传关联研究支持该区域在影响 V1aR 表达和社会行为方面的潜在作用。
The arginine vasopressin V1a receptor (V1aR) modulates social cognition and behavior in a wide variety of species. Variation in a repetitive microsatellite element in the 5' flanking region of the V1aR gene (AVPR1A) in rodents has been associated with variation in brain V1aR expression and in social behavior. In humans, the 5' flanking region of AVPR1A contains a tandem duplication of two ~350 bp, microsatellite-containing elements located approximately 3.5 kb upstream of the transcription start site. The first block, referred to as DupA, contains a polymorphic (GT)25 microsatellite; the second block, DupB, has a complex (CT)4-(TT)-(CT)8-(GT)24 polymorphic motif, known as RS3. Polymorphisms in RS3 have been associated with variation in sociobehavioral traits in humans, including autism spectrum disorders. Thus, evolution of these regions may have contributed to variation in social behavior in primates. We examined the structure of these regions in six ape, six monkey, and one prosimian species. Both tandem repeat blocks are present upstream of the AVPR1A coding region in five of the ape species we investigated, while monkeys have only one copy of this region. As in humans, the microsatellites within DupA and DupB are polymorphic in many primate species. Furthermore, both single (lacking DupB) and duplicated alleles (containing both DupA and DupB) are present in chimpanzee (Pan troglodytes) populations with allele frequencies of 0.795 and 0.205 for the single and duplicated alleles, respectively, based on the analysis of 47 wild-caught individuals. Finally, a phylogenetic reconstruction suggests two alternate evolutionary histories for this locus. There is no obvious relationship between the presence of the RS3 duplication and social organization in primates. However, polymorphisms identified in some species may be useful in future genetic association studies. In particular, the presence of both single and duplicated alleles in chimpanzees provides a unique opportunity to assess the functional role of this duplication in contributing to variation in social behavior in primates. While our initial studies show no signs of directional selection on this locus in chimps, pharmacological and genetic association studies support a potential role for this region in influencing V1aR expression and social behavior.
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