State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology and Kunming Primate Research Center, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.
BMC Evol Biol. 2011 Oct 12;11:298. doi: 10.1186/1471-2148-11-298.
Homeobox 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.
We 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.
RHOXF2 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.
同源盒基因是发育过程中的关键调控因子，它们通常高度保守，只有少数报道称它们经历了快速进化。RHOXF2 是灵长类动物的一个 X 连锁同源盒基因。它在睾丸中高度表达，可能在精子发生中发挥重要作用。由于男性生殖系统在进化过程中经常成为自然选择和/或性选择的目标，因此本研究旨在剖析 RHOXF2 在灵长类动物中的分子进化模式及其潜在的功能后果。
我们研究了 RHOXF2 在人类和 16 种非人类灵长类动物中的序列和拷贝数变异，以及在人类、黑猩猩、白眉长臂猿和恒河猴中的表达模式。基因拷贝数分析表明，多个灵长类动物谱系中存在平行的基因复制/缺失。我们的证据表明，11 种非人类灵长类动物具有一个 RHOXF2 拷贝，人类和 4 种旧世界猴具有两个拷贝，而黑猩猩至少具有 6 个拷贝。进一步分析表明，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。与非人类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它们的两个 RHOXF2 拷贝同质化。编码序列和系统发育分析表明，在灵长类动物进化过程中，RHOXF2 经历了多谱系的强烈正向选择，尤其是在人类和黑猩猩的起源时期。人类群体中所有 8 个编码区多态性位点均为非同义突变，暗示着持续的选择。基因表达分析表明，除了在生殖系统中的优先表达外，RHOXF2 还在大脑中表达。定量数据表明，在灵长类动物物种间存在表达模式的分化。
RHOXF2 是灵长类动物中快速进化的同源盒基因。RHOXF2 的快速进化和拷贝数变化是由对雄性生殖系统的达尔文正向选择驱动的，可能也受到中枢神经系统的驱动，这为理解同源盒基因在适应性进化中的作用提供了线索。
