Positive selection in MAOA gene is human exclusive:: determination of the putative amino acid change selected in the human lineage
Positive selection in MAOA gene is human exclusive:: determination of the putative amino acid change selected in the human lineage
复制标题
DOI：
10.1007/s00439-004-1179-6
复制
发表时间：
2004-10-01
期刊：
影响因子：
5.3
通讯作者：
Bertranpetit, J
中科院分区：
文献类型：
--
作者：
Andrés, AM;Soldevila, M;Bertranpetit, J
单胺氧化酶 A (MAOA) 是 X 连锁基因，负责多种神经递质和其他胺的脱氨和随后的降解。除其他活动外，该基因已被证明在运动、昼夜节律和疼痛敏感性中发挥作用，并对行为和认知产生关键影响。先前的研究报道了该基因的非中性进化可归因于人类谱系的正向选择。为了确定这种选择是人类独有的还是与其他物种共有的，我们对非人类物种（包括倭黑猩猩、黑猩猩、大猩猩和猩猩）的核苷酸变异模式进行了群体遗传分析。在所有分析的物种中都没有正选择的足迹，这表明正选择是最近出现的，并且是人类所独有的。为了确定哪些人类独特的基因变化可能导致了这种差异进化，对人类、黑猩猩和大猩猩的基因编码区进行了比较。该基因中仅存在一种人类独有的非保守变化：Glu151Lys。根据三维结构模型，这种人类替代会影响蛋白质二聚化，该模型预测了不可忽视的功能转变。这是目前在正选择过程中被选择固定在人类身上的唯一候选位置。物种间的差异分析表明，即使在人类谱系的正选择下，MAOA 基因在任何分析的谱系中都没有经历加速进化，并且 K-a/K-s 等工具不会检测到该基因的选择历史。
Monoamine oxidase A (MAOA) is the X-linked gene responsible for deamination and subsequent degradation of several neurotransmitters and other amines. Among other activities, the gene has been shown to play a role in locomotion, circadian rhythm, and pain sensitivity and to have a critical influence on behavior and cognition. Previous studies have reported a non-neutral evolution of the gene attributable to positive selection in the human lineage. To determine whether this selection was human-exclusive or shared with other species, we performed a population genetic analysis of the pattern of nucleotide variation in non-human species, including bonobo, chimpanzee, gorilla, and orangutan. Footprints of positive selection were absent in all analyzed species, suggesting that positive selection has been recent and unique to humans. To determine which human-unique genetic changes could have been responsible for this differential evolution, the coding region of the gene was compared between human, chimpanzee, and gorilla. Only one human exclusive non-conservative change is present in the gene: Glu151Lys. This human substitution affects protein dimerization according to a three-dimensional structural model that predicts a non-negligible functional shift. This is the only candidate position at present to have been selected to fixation in humans during an episode of positive selection. Divergence analysis among species has shown that, even under positive selection in the human lineage, the MAOA gene did not experience accelerated evolution in any of the analyzed lineages, and that tools such as K-a/K-s would not have detected the selective history of the gene.