Holbrook J D, Birdsey G M, Yang Z, Bruford M W, Danpure C J
MRC Laboratory for Molecular Cell Biology, University College London, England, United Kingdom.
Mol Biol Evol. 2000 Mar;17(3):387-400. doi: 10.1093/oxfordjournals.molbev.a026318.
The intermediary metabolic enzyme alanine:glyoxylate aminotransferase (AGT) is targeted to different organelles (mitochondria and/or peroxisomes) in different species. Possibly under the influence of dietary selection pressure, the subcellular distribution of AGT has changed on at least eight occasions during the evolution of mammals. AGT targeting is dependent on the variable use of two alternative transcription and translation initiation sites which determine whether or not the region encoding the N-terminal mitochondrial targeting sequence is contained within the open reading frame. In the present study, we sequenced the 5' region of the AGT gene, including both ancestral translation start sites, for 11 anthropoid primates and compared the results with data already available for two others. We show that while the more 3' of the two translation start sites is maintained in all species, the more 5' site has been lost in six species (five of seven catarrhines and one of six platyrrhines). In addition, the remaining two catarrhines, which have maintained the 5' translation start site, are predicted to have lost mitochondrial targeting by a different mechanism, possibly loss of the more 5' transcription start site. Analysis of the relative frequencies of nonsynonymous and synonymous mutations in the region encoding the extant or ancestral mitochondrial targeting sequences led us to suggest that there has been recent strong positive selection pressure to lose, or decrease the efficiency of, mitochondrial AGT targeting in several anthropoid lineages, and that the loss of mitochondrial targeting in this group of mammals is likely to have occurred on at least four, and possibly five, separate occasions.
乙醛酸转氨酶（AGT）在不同物种中定位于不同的细胞器（线粒体和/或过氧化物酶体）。可能在饮食选择压力的影响下，AGT的亚细胞分布在哺乳动物进化过程中至少发生了八次变化。AGT的靶向取决于两个交替转录和翻译起始位点的可变使用，这两个位点决定了编码N端线粒体靶向序列的区域是否包含在开放阅读框内。在本研究中，我们对11种类人猿灵长类动物的AGT基因5'区域进行了测序，包括两个祖先翻译起始位点，并将结果与另外两个物种已有的数据进行了比较。我们发现，虽然两个翻译起始位点中更靠3'端的位点在所有物种中都得以保留，但更靠5'端的位点在六个物种中已经丢失（七个狭鼻猿中的五个和六个阔鼻猿中的一个）。此外，保留了5'翻译起始位点的另外两个狭鼻猿，预计通过不同的机制失去了线粒体靶向能力，可能是更靠5'端的转录起始位点丢失。对编码现存或祖先线粒体靶向序列区域中非同义突变和同义突变相对频率的分析使我们认为，最近在几个类人猿谱系中存在强烈的正选择压力，导致线粒体AGT靶向能力丧失或效率降低，并且在这组哺乳动物中，线粒体靶向能力的丧失可能至少发生了四次，甚至可能是五次独立的事件。
