Rapid evolution and copy number variation of primate RHOXF2, an X-linked homeobox gene involved in male reproduction and possibly brain function
Rapid evolution and copy number variation of primate RHOXF2, an X-linked homeobox gene involved in male reproduction and possibly brain function
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灵长类动物 RHOXF2 的快速进化和拷贝数变异，一种 X 连锁同源盒基因，涉及雄性生殖和可能的大脑功能
作者：
Ao;Yin;Hui Zhang;Cheng;Jin;Rui Zhang;Jun Che;B. Su
背景同源异型盒基因是发育过程中的关键调控基因，它们一般高度保守，只有少数报道过快速进化的情况。RHOXF 2是灵长类中的X连锁同源盒基因。它在睾丸中高度表达，可能在精子发生中起重要作用。由于雄性生殖系统往往是自然和/或性选择在进化过程中的目标，在这项研究中，我们的目的是解剖的模式，在灵长类动物的RHOXF 2的分子进化及其潜在的功能consequence.ResultsWe研究的序列和拷贝数的变化，RHOXF 2在人类和16个非人灵长类动物物种，以及在人类，黑猩猩，白眉长臂猿和恒河猴的表达模式。基因拷贝数分析表明，在多个灵长类谱系中存在平行的基因复制/丢失。我们的证据表明，11种非人类灵长类动物有一个RHOXF 2拷贝，人类和四种旧大陆猴中有两个拷贝，黑猩猩中至少有6个拷贝。进一步的分析表明，灵长类动物中的基因复制可能是由基因区域侧翼的内源性逆转录病毒（ERV）序列介导的。与非人灵长类动物形成鲜明对比的是，人类似乎通过ERV介导的非等位基因重组机制使其两个RHOXF 2拷贝均质化。编码序列和系统发育分析表明，在灵长类进化过程中，特别是在人类和黑猩猩的起源过程中，RHOXF 2基因存在多谱系的强正选择。所有8个编码区多态性位点在人群中是非同义的，这意味着正在进行的选择。基因表达分析表明，RHOXF 2除了在生殖系统中优先表达外，还在脑中表达。结论RHOXF 2基因在灵长类动物中是一个快速进化的同源异型盒基因。RHOXF 2的快速进化和拷贝数的变化是由达尔文正选择作用于雄性生殖系统和可能也作用于中枢神经系统驱动的，这为理解同源异型盒基因在适应性进化中的作用提供了线索。
BackgroundHomeobox genes are the key regulators during development, and they are in general highly conserved with only a few reported cases of rapid evolution. RHOXF2 is an X-linked homeobox gene in primates. It is highly expressed in the testicle and may play an important role in spermatogenesis. As male reproductive system is often the target of natural and/or sexual selection during evolution, in this study, we aim to dissect the pattern of molecular evolution of RHOXF2 in primates and its potential functional consequence.ResultsWe studied sequences and copy number variation of RHOXF2 in humans and 16 nonhuman primate species as well as the expression patterns in human, chimpanzee, white-browed gibbon and rhesus macaque. The gene copy number analysis showed that there had been parallel gene duplications/losses in multiple primate lineages. Our evidence suggests that 11 nonhuman primate species have one RHOXF2 copy, and two copies are present in humans and four Old World monkey species, and at least 6 copies in chimpanzees. Further analysis indicated that the gene duplications in primates had likely been mediated by endogenous retrovirus (ERV) sequences flanking the gene regions. In striking contrast to non-human primates, humans appear to have homogenized their two RHOXF2 copies by the ERV-mediated non-allelic recombination mechanism. Coding sequence and phylogenetic analysis suggested multi-lineage strong positive selection on RHOXF2 during primate evolution, especially during the origins of humans and chimpanzees. All the 8 coding region polymorphic sites in human populations are non-synonymous, implying on-going selection. Gene expression analysis demonstrated that besides the preferential expression in the reproductive system, RHOXF2 is also expressed in the brain. The quantitative data suggests expression pattern divergence among primate species.ConclusionsRHOXF2 is a fast-evolving homeobox gene in primates. The rapid evolution and copy number changes of RHOXF2 had been driven by Darwinian positive selection acting on the male reproductive system and possibly also on the central nervous system, which sheds light on understanding the role of homeobox genes in adaptive evolution.
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影响因子：
2.7
作者：
Liu, YH;Tang, ZQ;Maxson, RE
通讯作者：
Maxson, RE
影响因子：
9.8
作者：
Chen, FC;Li, WH
通讯作者：
Li, WH
影响因子：
4.4
作者：
Ackerman, SL;Knowles, BB
通讯作者：
Knowles, BB
多个器官发育所需的 Pitx2 剂量。
DOI：
10.1242/dev.126.20.4643
发表时间：
1999
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Gage,PJ;Suh,H;Camper,SA
通讯作者：
Camper,SA
影响因子：
9.8
作者：
Perry, George H.;Ben-Dor, Amir;Lee, Charles
通讯作者：
Lee, Charles