Intrasubtype reassortments cause adaptive amino acid replacements in H3N2 influenza genes.
Intrasubtype reassortments cause adaptive amino acid replacements in H3N2 influenza genes.
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DOI：
10.1371/journal.pgen.1004037
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发表时间：
2014-01
期刊：
影响因子：
4.5
通讯作者：
Bazykin GA
中科院分区：
文献类型：
--
作者：
Neverov AD;Lezhnina KV;Kondrashov AS;Bazykin GA
逆转录和点突变是甲型流感病毒多样性的两个主要贡献者;然而，这两个过程之间的联系尚不清楚。有人认为，重组引起的氨基酸变化率的暂时增加，因为病毒蛋白适应新的遗传环境，但这种现象还没有得到系统的研究。在这里，我们使用系统发育的方法来推断8个片段的甲型H3 N2流感病毒，因为它在1968年出现在人类之间的重配事件。然后，我们研究了发生在基因编码的每个片段的氨基酸替换后的retransmittations。在八个基因中的五个（NA、M1、HA、PB 1和NS 1）中，重配事件导致后代系统发育分支上的氨基酸替换率的瞬时增加。在NA和HA中，重组后的替换富含平行和/或反向替换;相反，负责抗原簇之间差异的位点（HA中）和阳性选择位点（NA中）的替换在其中代表性不足。重配后适应性游走有助于甲型流感的适应性进化：在NA中，平均重配事件在重配基因中引起至少2.1个氨基酸替换，平均每个进化的重配后谱系有0.43个氨基酸替换;并且所有氨基酸替换中至少有10.9%是由重配引起的。甲型流感病毒是一种快速进化的病毒，其基因组由八种不同的RNA分子组成，称为片段。当一个细胞被多种病毒株共同感染时，这种遗传结构允许形成新的片段组合，这一过程称为重配。虽然“抗原漂移”--改变病毒蛋白抗原特性的点突变的持续积累过程--是季节性流感的主要原因，但最严重的大流行是由新的抵抗菌株的传播和相关的根本“抗原转移”引起的。然而，这两种类型的过程之间的关联还没有得到系统的研究。在这里，我们使用广泛可用的全基因组测序数据甲型流感H3 N2亚型推断亚型内重配事件的进化时间，并研究点氨基酸变化的替代模式，随后的重组。我们发现，重组后往往迅速更换，这可能会补偿与重组或探索新的访问健身高峰健身的损失。这些发现可能与预测未来甲型流感大流行株有关。
Reassortments and point mutations are two major contributors to diversity of Influenza A virus; however, the link between these two processes is unclear. It has been suggested that reassortments provoke a temporary increase in the rate of amino acid changes as the viral proteins adapt to new genetic environment, but this phenomenon has not been studied systematically. Here, we use a phylogenetic approach to infer the reassortment events between the 8 segments of influenza A H3N2 virus since its emergence in humans in 1968. We then study the amino acid replacements that occurred in genes encoded in each segment subsequent to reassortments. In five out of eight genes (NA, M1, HA, PB1 and NS1), the reassortment events led to a transient increase in the rate of amino acid replacements on the descendant phylogenetic branches. In NA and HA, the replacements following reassortments were enriched with parallel and/or reversing replacements; in contrast, the replacements at sites responsible for differences between antigenic clusters (in HA) and at sites under positive selection (in NA) were underrepresented among them. Post-reassortment adaptive walks contribute to adaptive evolution in Influenza A: in NA, an average reassortment event causes at least 2.1 amino acid replacements in a reassorted gene, with, on average, 0.43 amino acid replacements per evolving post-reassortment lineage; and at least ∼9% of all amino acid replacements are provoked by reassortments. Influenza A is a rapidly evolving virus with genome composed of eight distinct RNA molecules called segments. This genetic structure allows formation of new combinations of segments when a cell is coinfected by multiple viral strains, in a process called reassortment. While “antigenic drift” – the process of continuous accumulation of point mutations that change the antigenic properties of the viral proteins – is mainly responsible for the seasonal flu, the heaviest pandemics were caused by spread of novel reassortant strains and the associated radical “antigenic shift”. However, the association between these two types of processes has not been studied systematically. Here, we use the extensive available complete-genome sequencing data for Influenza A H3N2 subtype to infer the evolutionary timings of within-subtype reassortment events, and study the patterns of point amino acid-changing replacements that followed reassortments. We find that reassortments were often rapidly followed by replacements, which possibly compensated for the loss of fitness associated with the reassortment or explored newly accessible fitness peaks. These findings may be relevant for prediction of future pandemic strains of Influenza A.
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影响因子：
3.7
作者：
Khiabanian H;Trifonov V;Rabadan R
通讯作者：
Rabadan R
DOI：
10.1073/pnas.1113300109
发表时间：
2012-02-28
影响因子：
11.1
作者：
Greenbaum, Benjamin D.;Li, Olive T. W.;Rabadan, Raul
通讯作者：
Rabadan, Raul
影响因子：
3.9
作者：
dos Reis, Mario;Hay, Alan J.;Goldstein, Richard A.
通讯作者：
Goldstein, Richard A.
影响因子：
64.8
作者：
Imai, Masaki;Watanabe, Tokiko;Hatta, Masato;Das, Subash C.;Ozawa, Makoto;Shinya, Kyoko;Zhong, Gongxun;Hanson, Anthony;Katsura, Hiroaki;Watanabe, Shinji;Li, Chengjun;Kawakami, Eiryo;Yamada, Shinya;Kiso, Maki;Suzuki, Yasuo;Maher, Eileen A.;Neumann, Gabriele;Kawaoka, Yoshihiro
通讯作者：
Kawaoka, Yoshihiro
DOI：
10.1126/science.1213362
发表时间：
2012-06-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Herfst S;Schrauwen EJ;Linster M;Chutinimitkul S;de Wit E;Munster VJ;Sorrell EM;Bestebroer TM;Burke DF;Smith DJ;Rimmelzwaan GF;Osterhaus AD;Fouchier RA
通讯作者：
Fouchier RA