Li W H, Tanimura M, Sharp P M
Center for Demographic and Population Genetics, University of Texas, Houston 77225.
Mol Biol Evol. 1988 Jul;5(4):313-30. doi: 10.1093/oxfordjournals.molbev.a040503.
The acquired immune deficiency syndrome (AIDS), caused by a retrovirus called human immunodeficiency virus (HIV), has become a pandemic. A knowledge of the rate of nucleotide substitution in HIV and of the history and pattern of spread of the virus is important for understanding the epidemiology and pathogenesis of AIDS and for developing therapies and vaccine strategies. A new model has been developed and used to estimate the substitution rates in various regions in the HIV genome. The rate of nonsynonymous (amino acid-changing) substitution is lowest in the regions coding for the capsid proteins and the reverse transcriptase, being approximately 1.7 X 10(-3) nucleotide substitutions/site/year. The nonsynonymous rate is extremely high (14 X 10(-3] in the hypervariable regions of the envelope gene, suggesting extremely rapid change in viral antigenicity. The nonsynonymous rates in the other coding regions are between 3 X 10(-3) and 7 X 10(-3). The average synonymous rate for the HIV genome is 10 X 10(-3). These rates are 10(6) times greater than the rates in DNA genomes and at least as high as the rates in other RNA viruses. Evidence is provided for a case of recombination between different HIV strains. Our analysis suggests that the AIDS virus had existed in central Africa before 1960 and spread to North America before the mid 1970s. The evolutionary relationships among HIV isolates are inferred from nucleotide sequence data, and the result is consistent with the view that AIDS spread from Haiti to the United States.
获得性免疫缺陷综合征（艾滋病）由一种名为人类免疫缺陷病毒（HIV）的逆转录病毒引起，已成为一种大流行病。了解HIV中的核苷酸替换率以及该病毒的传播历史和模式，对于理解艾滋病的流行病学和发病机制以及制定治疗方法和疫苗策略至关重要。一种新模型已被开发出来并用于估计HIV基因组不同区域的替换率。在编码衣壳蛋白和逆转录酶的区域，非同义（氨基酸改变）替换率最低，约为1.7×10⁻³核苷酸替换/位点/年。在包膜基因的高变区，非同义率极高（14×10⁻³），这表明病毒抗原性变化极快。其他编码区域的非同义率在3×10⁻³至7×10⁻³之间。HIV基因组的平均同义率为10×10⁻³。这些速率比DNA基因组中的速率高10⁶倍，且至少与其他RNA病毒中的速率一样高。提供了不同HIV毒株之间发生重组的证据。我们的分析表明，艾滋病病毒在1960年前就已存在于中非，并在20世纪70年代中期之前传播到了北美。从核苷酸序列数据推断HIV分离株之间的进化关系，结果与艾滋病从海地传播到美国的观点一致。
