Saitou N, Nei M
Center for Demographic and Population Genetics, University of Texas, Houston 77225.
Mol Biol Evol. 1986 Jan;3(1):57-74. doi: 10.1093/oxfordjournals.molbev.a040381.
The nucleotide sequences of four genes of the influenza A virus (nonstructural protein, matrix protein, and a few subtypes of hemagglutinin and neuraminidase) are compiled for a large number of strains isolated from various locations and years, and the evolutionary relationship of the sequences is investigated. It is shown that all of these genes or subtypes are highly polymorphic and that the polymorphic sequences (alleles) are subject to rapid turnover in the population, their average age being much less than that of higher organisms. Phylogenetic analysis suggests that most polymorphic sequences within a subtype or a gene appeared during the last 80 years and that the divergence among the subtypes of hemagglutinin genes might have occurred during the last 300 years. The high degree of polymorphism in this RNA virus is caused by an extremely high rate of mutation, estimated to be 0.01/nucleotide site/year. Despite the high rate of mutation, most influenza virus genes are apparently subject to purifying selection, and the rate of nucleotide substitution is substantially lower than the mutation rate. There is considerable variation in the substitution rate among different genes, and the rate seems to be lower in nonhuman viral strains than in human strains. The difference might be responsible for the so-called freezing effect in some viral strains.
对从不同地点和年份分离出的大量甲型流感病毒毒株的四个基因（非结构蛋白、基质蛋白以及几种血凝素和神经氨酸酶亚型）的核苷酸序列进行了汇编，并研究了这些序列的进化关系。结果表明，所有这些基因或亚型都具有高度多态性，并且多态性序列（等位基因）在种群中会快速更替，其平均存在时间远短于高等生物。系统发育分析表明，一个亚型或一个基因内的大多数多态性序列出现在过去80年内，血凝素基因各亚型之间的分化可能发生在过去300年内。这种RNA病毒的高度多态性是由极高的突变率引起的，估计为0.01/核苷酸位点/年。尽管突变率很高，但大多数流感病毒基因显然受到纯化选择，核苷酸替换率明显低于突变率。不同基因的替换率存在相当大的差异，非人病毒毒株的替换率似乎低于人病毒毒株。这种差异可能是某些病毒毒株中所谓“冻结效应”的原因。
