Patterns of intra- and interhost nonsynonymous variation reveal strong purifying selection in dengue virus
Patterns of intra- and interhost nonsynonymous variation reveal strong purifying selection in dengue virus
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DOI：
10.1128/jvi.77.20.11296-11298.2003
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发表时间：
2003-10-01
影响因子：
5.4
通讯作者：
Holmes, EC
中科院分区：
文献类型：
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作者：
Holmes, EC
相当大的不确定性围绕着节肢动物传播的RNA病毒（虫媒病毒）的进化速率和选择压力。特别是，目前还不清楚为什么虫媒病毒如登革病毒在个体人类和蚊子中显示出大量的遗传变异，但长期的氨基酸取代率很低。为了解决这个问题，我比较了在不同水平的进化分歧采样的登革热病毒种群的非同义变异模式。虽然非同义变异是丰富的病毒种群内的个人，有一个显着的减少，在宿主间的比较非同义突变的频率。此外，宿主内的遗传变异对应于一个随机的突变模式，和大多数的主机内表现出非同义变异的网站是不变的，在更深的系统发育水平。这种长期非同义变异的丧失是广泛的纯化选择的标志，使得超过90%的所有非同义突变是有害的。因此，虽然虫媒病毒能够成功地适应不同的细胞类型，但它们的特征是高速率的有害突变。
Considerable uncertainty surrounds the evolutionary rates of and selection pressures acting on arthropod-borne RNA viruses (arboviruses). In particular, it is unclear why arboviruses such as dengue virus show substantial genetic variation within individual humans and mosquitoes yet low long-term rates of amino acid substitution. To address this question, I compared patterns of nonsynonymous variation in populations of dengue virus sampled at different levels of evolutionary divergence. Although nonsynonymous variation was abundant in viral populations within individual humans, there was a marked reduction in the frequency of nonsynonymous mutations in interhost comparisons. Moreover, intrahost genetic variation corresponded to a random pattern of mutation, and most of the sites that exhibited nonsynonymous variation within hosts were invariant at deeper phylogenetic levels. This loss of long-term nonsynonymous variation is the signature of extensive purifying selection such that more than 90% of all nonsynonymous mutations are deleterious. Consequently, although arboviruses are able to successfully adapt to diverse cell types, they are characterized by a high rate of deleterious mutation.