Malik Harmit S, Henikoff Steven
Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
PLoS Genet. 2005 Oct;1(4):e44. doi: 10.1371/journal.pgen.0010044.
Eukaryotic genomes can usurp enzymatic functions encoded by mobile elements for their own use. A particularly interesting kind of acquisition involves the domestication of retroviral envelope genes, which confer infectious membrane-fusion ability to retroviruses. So far, these examples have been limited to vertebrate genomes, including primates where the domesticated envelope is under purifying selection to assist placental function. Here, we show that in Drosophila genomes, a previously unannotated gene (CG4715, renamed Iris) was domesticated from a novel, active Kanga lineage of insect retroviruses at least 25 million years ago, and has since been maintained as a host gene that is expressed in all adult tissues. Iris and the envelope genes from Kanga retroviruses are homologous to those found in insect baculoviruses and gypsy and roo insect retroviruses. Two separate envelope domestications from the Kanga and roo retroviruses have taken place, in fruit fly and mosquito genomes, respectively. Whereas retroviral envelopes are proteolytically cleaved into the ligand-interaction and membrane-fusion domains, Iris appears to lack this cleavage site. In the takahashii/suzukii species groups of Drosophila, we find that Iris has tandemly duplicated to give rise to two genes (Iris-A and Iris-B). Iris-B has significantly diverged from the Iris-A lineage, primarily because of the "invention" of an intron de novo in what was previously exonic sequence. Unlike domesticated retroviral envelope genes in mammals, we find that Iris has been subject to strong positive selection between Drosophila species. The rapid, adaptive evolution of Iris is sufficient to unambiguously distinguish the phylogenies of three closely related sibling species of Drosophila (D. simulans, D. sechellia, and D. mauritiana), a discriminative power previously described only for a putative "speciation gene." Iris represents the first instance of a retroviral envelope-derived host gene outside vertebrates. It is also the first example of a retroviral envelope gene that has been found to be subject to positive selection following its domestication. The unusual selective pressures acting on Iris suggest that it is an active participant in an ongoing genetic conflict. We propose a model in which Iris has "switched sides," having been recruited by host genomes to combat baculoviruses and retroviruses, which employ homologous envelope genes to mediate infection.
真核生物基因组可以盗用移动元件编码的酶功能以供自身使用。一种特别有趣的获取方式涉及逆转录病毒包膜基因的驯化，这些基因赋予逆转录病毒感染性膜融合能力。到目前为止，这些例子仅限于脊椎动物基因组，包括灵长类动物，其中驯化的包膜处于纯化选择之下以协助胎盘功能。在这里，我们表明，在果蝇基因组中，一个以前未注释的基因（CG4715，重新命名为Iris）至少在2500万年前从一种新型的、活跃的昆虫逆转录病毒Kanga谱系驯化而来，此后一直作为一个在所有成年组织中表达的宿主基因保留下来。Iris和来自Kanga逆转录病毒的包膜基因与在昆虫杆状病毒以及吉普赛和袋鼠昆虫逆转录病毒中发现的基因同源。分别在果蝇和蚊子基因组中发生了两次从Kanga和袋鼠逆转录病毒的独立包膜驯化。虽然逆转录病毒包膜被蛋白水解切割成配体相互作用和膜融合结构域，但Iris似乎缺乏这个切割位点。在果蝇的高桥/铃木物种组中，我们发现Iris串联重复产生了两个基因（Iris-A和Iris-B）。Iris-B与Iris-A谱系有显著差异，主要是因为在以前的外显子序列中从头“发明”了一个内含子。与哺乳动物中驯化的逆转录病毒包膜基因不同，我们发现Iris在果蝇物种之间受到强烈的正选择。Iris的快速适应性进化足以明确区分果蝇三个密切相关的同胞物种（拟暗果蝇、塞舌尔果蝇和毛里求斯果蝇）的系统发育，这种区分能力以前仅针对一个假定的“物种形成基因”进行过描述。Iris代表了脊椎动物以外的逆转录病毒包膜衍生宿主基因的第一个实例。它也是第一个被发现驯化后受到正选择的逆转录病毒包膜基因的例子。作用于Iris的异常选择压力表明它是正在进行的基因冲突中的积极参与者。我们提出了一个模型，其中Iris已经“转变立场”，被宿主基因组招募来对抗杆状病毒和逆转录病毒，这些病毒利用同源包膜基因介导感染。
