Codon bias and frequency-dependent selection on the hemagglutinin epitopes of influenza A virus
Codon bias and frequency-dependent selection on the hemagglutinin epitopes of influenza A virus
复制标题
DOI：
10.1073/pnas.1132114100
复制
发表时间：
2003-06-10
影响因子：
11.1
通讯作者：
Dushoff, J
中科院分区：
文献类型：
--
作者：
Plotkin, JB;Dushoff, J
虽然人类甲型流感病毒的表面蛋白进化迅速，不断产生抗原性变异，但病毒内部基因的突变是非常缓慢的。本文分析了甲型流感病毒三个基因在过去二十年中的序列进化。我们研究密码子的使用作为基因的区别性特征，甚至残基特异性的多样化和纯化选择。非随机密码子选择会增加或降低有效局部替换率。我们证明，相对于其他流感病毒基因的密码子，血凝素的密码子，特别是抗体结合区的密码子，明显偏向于替换点突变。我们讨论了这些偏向的进化解释和对血凝素抗原进化的影响。我们还介绍了使用序列数据的信息论方法。检测最近的正选择区域和潜在的蛋白质构象变化。
Although the surface proteins of human influenza A virus evolve rapidly and continually produce antigenic variants, the internal viral genes acquire mutations very gradually. In this paper, we analyze the sequence evolution of three influenza A genes over the past two decades. We study codon usage as a discriminating signature of gene and even residue-specific diversifying and purifying selection. Non-random codon choice can increase or decrease the effective local substitution rate. We demonstrate that the codons of hemagglutinin, particularly those in the antibody-combining regions, are significantly biased toward substitutional point mutations relative to the codons of other influenza virus genes. We discuss the evolutionary interpretation and implications of these biases for hemagglutinin's antigenic evolution. We also introduce information-theoretic methods that use sequence data. to detect regions of recent positive selection and potential protein conformational changes.