Centre for Vascular Research, Faculty of Medicine, University of New South Wales, Sydney 2052, Australia.
J Virol. 2011 Sep;85(17):9139-46. doi: 10.1128/JVI.00658-11. Epub 2011 Jun 22.
It is known that the human immune proteins APOBEC3G and -F (hA3G/F) can inhibit Vif-deficient HIV by G-to-A mutation; however, the roles of these enzymes in the evolution of HIV are debated. We argue that if evolutionary pressure from hA3G/F exists there should be evidence of their imprint on the HIV genome in the form of (i) underrepresentation of hA3G/F target motifs (e.g., TGGG [targeted position is underlined]) and overrepresentation of product motifs (e.g., TAGG) and/or (ii) an increase in the ratio of nonsynonymous to synonymous (NS/S) G-to-A changes among hA3G/F target motifs and a decrease of NS/S A-to-G changes among hA3G/F product motifs. To test the first hypothesis, we studied the representation of hA3G/F target and product motifs in 1,932 complete HIV-1 genomes using Markov models. We found that the highly targeted motifs are not underrepresented and their product motifs are not overrepresented. To test the second hypothesis, we determined the NS/S G↔A changes among the hA3G/F target and product motifs in 1,540 complete sets of nine HIV-1 genes. The NS/S changes did not show an increasing/decreasing trend within the target/product motifs, but the NS/S changes within the motif AG was exceptionally low. We observed the same pattern by analyzing 740 human genes. Given that hA3G/F do not act on the human genome, this suggests a small NS/S change within AG has arisen by other mechanisms. We therefore find no evidence of an evolutionary footprint of hA3G/F. We postulate several mechanisms to explain why the HIV-1 genome does not contain the hA3G/F footprint.
已知人类免疫蛋白 APOBEC3G 和 -F（hA3G/F）可以通过 G 到 A 的突变抑制 Vif 缺陷型 HIV；然而，这些酶在 HIV 进化中的作用仍存在争议。我们认为，如果 hA3G/F 存在进化压力，那么在 HIV 基因组中应该有证据表明它们的印记，表现为（i）hA3G/F 靶标基序（例如，TGGG[靶向位置加下划线]）的代表性不足和产物基序（例如，TAGG）的代表性过高，和/或（ii）hA3G/F 靶标基序中非同义到同义（NS/S）G 到 A 变化的比例增加，以及 hA3G/F 产物基序中 NS/S A 到 G 变化的减少。为了检验第一个假设，我们使用马尔可夫模型研究了 1932 个完整 HIV-1 基因组中 hA3G/F 靶标和产物基序的代表性。我们发现，高度靶向的基序没有代表性不足，其产物基序也没有代表性过高。为了检验第二个假设，我们确定了 1540 个完整的九组 HIV-1 基因中 hA3G/F 靶标和产物基序中的 NS/S G↔A 变化。NS/S 变化在靶标/产物基序中没有表现出增加/减少的趋势，但基序 AG 中的 NS/S 变化异常低。通过分析 740 个人类基因，我们观察到了相同的模式。由于 hA3G/F 不作用于人类基因组，这表明 AG 内的 NS/S 变化是由其他机制引起的。因此，我们没有发现 hA3G/F 的进化足迹的证据。我们提出了几种机制来解释为什么 HIV-1 基因组不包含 hA3G/F 的足迹。
