Evolution of the primate APOBEC3A cytidine deaminase gene and identification of related coding regions.
Evolution of the primate APOBEC3A cytidine deaminase gene and identification of related coding regions.
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DOI：
10.1371/journal.pone.0030036
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Vartanian JP
中科院分区：
文献类型：
--
作者：
Henry M;Terzian C;Peeters M;Wain-Hobson S;Vartanian JP
APOBEC 3基因簇编码六种具有单链DNA（ssDNA）底物特异性的胞苷脱氨酶（A3 A-C、A3 DE、A3 F-H）。目前A3 A是唯一一种可以启动线粒体和核DNA催化的酶。人A3 A表达起始于两个不同的甲硫氨酸密码子M1或M13，这两个密码子都在适当但次优的Kozak环境中。在本研究中，我们分析了A3 A基因在广泛的12个灵长类动物，包括新世界猴，旧世界猴和人科动物之间的遗传多样性。在所有灵长类动物的外显子1-4中观察到序列变异，总氨基酸变异高达31%。重要的是，3个人类密码子M1突变为苏氨酸密码子或缬氨酸密码子，而5/12的灵长类动物中发现了强Kozak M1或M13密码子。在分析的过程中，两个新的非功能性A3 A相关的片段被确定在染色体4和8 kb的A3基因座上游。灵长类动物A3 A基因之间的这种定性和定量变化表明，随着对这种日益重要的酶的了解越来越多，功能上的细微差异可能会随之而来。
The APOBEC3 gene cluster encodes six cytidine deaminases (A3A-C, A3DE, A3F-H) with single stranded DNA (ssDNA) substrate specificity. For the moment A3A is the only enzyme that can initiate catabolism of both mitochondrial and nuclear DNA. Human A3A expression is initiated from two different methionine codons M1 or M13, both of which are in adequate but sub-optimal Kozak environments. In the present study, we have analyzed the genetic diversity among A3A genes across a wide range of 12 primates including New World monkeys, Old World monkeys and Hominids. Sequence variation was observed in exons 1–4 in all primates with up to 31% overall amino acid variation. Importantly for 3 hominids codon M1 was mutated to a threonine codon or valine codon, while for 5/12 primates strong Kozak M1 or M13 codons were found. Positive selection was apparent along a few branches which differed compared to positive selection in the carboxy-terminal of A3G that clusters with A3A among human cytidine deaminases. In the course of analyses, two novel non-functional A3A-related fragments were identified on chromosome 4 and 8 kb upstream of the A3 locus. This qualitative and quantitative variation among primate A3A genes suggest that subtle differences in function might ensue as more light is shed on this increasingly important enzyme.
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影响因子：
64.5
作者：
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通讯作者：
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影响因子：
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Malim, MH
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