Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK.
BMC Evol Biol. 2010 Jun 17;10:182. doi: 10.1186/1471-2148-10-182.
Many homeobox genes show remarkable conservation between divergent animal phyla. In contrast, the ARGFX (Arginine-fifty homeobox) homeobox locus was identified in the human genome but is not present in mouse or invertebrates. Here we ask when and how this locus originated and examine its pattern of molecular evolution.
Phylogenetic and phylogenomic analyses suggest that ARGFX originated by gene duplication from Otx1, Otx2 or Crx during early mammalian evolution, most likely on the stem lineage of the eutherians. ARGFX diverged extensively from its progenitor homeobox gene and its exons have been functional and subject to purifying selection through much of placental mammal radiation. Surprisingly, the coding region is disrupted in most mammalian genomes analysed, with human being the only mammal identified in which the full open reading frame is retained. Indeed, we describe a transcript from human testis that has the potential to encode the full deduced protein.
The unusual pattern of evolution suggests that the ARGFX gene may encode a functional RNA or alternatively it may have 'flickered' between functional and non-functional states in the evolutionary history of mammals, particularly in the period when many mammalian lineages diverged within a relatively short time span.
许多同源盒基因在不同的动物门之间表现出显著的保守性。相比之下，ARGFX（精氨酸五十同源盒）同源盒基因座在人类基因组中被识别，但在老鼠或无脊椎动物中不存在。在这里，我们要问这个基因座是什么时候以及如何产生的，并研究其分子进化模式。
系统发育和系统基因组学分析表明，ARGFX 是在早期哺乳动物进化过程中由 Otx1、Otx2 或 Crx 的基因复制产生的，最有可能是在真兽类的主干谱系上。ARGFX 与其祖先进化的同源盒基因广泛分化，其外显子在胎盘哺乳动物辐射的大部分过程中一直具有功能，并受到纯化选择的影响。令人惊讶的是，该编码区在大多数分析的哺乳动物基因组中被破坏，而人类是唯一被确定保留完整开放阅读框的哺乳动物。事实上，我们描述了一种来自人类睾丸的转录本，它有可能编码完整的推定蛋白。
这种不寻常的进化模式表明，ARGFX 基因可能编码一种功能性 RNA，或者它可能在哺乳动物的进化历史中，特别是在许多哺乳动物谱系在相对较短的时间内分化的时期，在功能性和非功能性状态之间“闪烁”。
