Adaptation to different human populations by HIV-1 revealed by codon-based analyses.
Adaptation to different human populations by HIV-1 revealed by codon-based analyses.
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基于密码子的分析揭示了对HIV-1对不同人群的适应。
DOI：
10.1371/journal.pcbi.0020062
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发表时间：
2006-06-23
影响因子：
4.3
通讯作者：
Leigh Brown, Andrew J.
中科院分区：
文献类型：
--
作者：
Kosakovsky Pond, Sergei L.;Frost, Simon D. W.;Grossman, Zehava;Gravenor, Michael B.;Richman, Douglas D.;Leigh Brown, Andrew J.
有几种基于密码子的方法可用于检测蛋白质编码序列的适应性进化，但迄今为止，没有一种方法能特异性地识别两个种群中差异选择的位点，尽管这种种群之间的比较在历史上对识别自然选择的作用很有用。我们已经开发了两个固定效应的最大似然方法：一个用于识别密码子的位置显示选择模式，坚持在人口和另一个用于检测是否选择操作差异从两个不同的人口抽样的基因的单个密码子。将这些方法应用于感染遗传上不同的人类宿主的两个HIV群体，我们发现很少有积极选择的氨基酸位点在群体中持续存在;其他变化仅在系统发育树的顶端检测到，并且从长远来看是有害的。此外，我们已经确定了蛋白酶和逆转录酶中的7个氨基酸位点，这些位点在两个样本中有差异地选择，证明了HIV对人类群体的特定群体水平适应。尽管为调查艾滋病毒遗传多样性和研制有效疫苗作出了努力，但对于前者对后者的偏见程度仍然没有达成共识。实验研究表明，HIV和SIV会选择逃避细胞介导的免疫，有时速度非常快。相反，逃逸突变体可能会被选择来抵抗传播，那么个体内的这种选择对整个HIV流行人群的基因型有多大影响呢？Kosakovsky Pond，Leigh Brown和同事们开发了一种新的统计方法来解决这个问题。使用全球最丰富的HIV亚型（C亚型）的序列，作者直接比较了感染遗传上不同人群的相同亚型的病毒。他们显示，在个体中选择的氨基酸位点中至少有一半不是在群体水平上选择的，并且他们确定了RT基因中的六个氨基酸位点在群体之间有差异地选择。我们现在可以在个体和群体成分之间划分分子适应性，无论候选疫苗中包含什么基因，在目标人群中。这些方法在艾滋病毒世界之外也很重要，在那里，类似的问题出现在病原体毒力进化的更普遍问题中。
Several codon-based methods are available for detecting adaptive evolution in protein-coding sequences, but to date none specifically identify sites that are selected differentially in two populations, although such comparisons between populations have been historically useful in identifying the action of natural selection. We have developed two fixed effects maximum likelihood methods: one for identifying codon positions showing selection patterns that persist in a population and another for detecting whether selection is operating differentially on individual codons of a gene sampled from two different populations. Applying these methods to two HIV populations infecting genetically distinct human hosts, we have found that few of the positively selected amino acid sites persist in the population; the other changes are detected only at the tips of the phylogenetic tree and appear deleterious in the long term. Additionally, we have identified seven amino acid sites in protease and reverse transcriptase that are selected differentially in the two samples, demonstrating specific population-level adaptation of HIV to human populations. Despite the efforts devoted to surveying HIV genetic diversity and the development of an effective vaccine, there is still no consensus on the extent to which the former prejudices the latter. Experimental studies show that escape from cell-mediated immunity is selected for in HIV and SIV, and sometimes very quickly. Conversely, escape mutants may be selected against at transmission, so how much does this selection within individuals influence the genotype of the circulating HIV population overall? Kosakovsky Pond, Leigh Brown, and colleagues have developed a new statistical approach to address this question. Using sequences from the globally most abundant HIV subtype (subtype C), the authors directly compared virus of the same subtype infecting genetically different human populations. They show at least half of the amino acid sites selected within individuals are not selected at a population level, and they identify six amino acid sites in the RT gene that are selected differentially between populations. We can now partition molecular adaptation between individual and population components for whatever genes may be included in candidate vaccines, in the target populations themselves. The methods are also important beyond the HIV world, where analogous issues arise in the more general question of the evolution of virulence in pathogens.
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影响因子：
15.3
作者：
Kelleher, A D;Long, C;Holmes, E C;Allen, R L;Wilson, J;Conlon, C;Workman, C;Shaunak, S;Olson, K;Goulder, P;Brander, C;Ogg, G;Sullivan, J S;Dyer, W;Jones, I;McMichael, A J;Rowland-Jones, S;Phillips, R E
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影响因子：
3.9
作者：
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通讯作者：
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影响因子：
5.4
作者：
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通讯作者：
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影响因子：
64.8
作者：
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通讯作者：
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影响因子：
10.7
作者：
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通讯作者：
Rambaut, A