ICBM, Universidad de Chile, Santiago, Chile.
Biol Res. 2010;43(2):149-63. Epub 2010 Sep 24.
We examined 103 nucleotide sequences of the HIV-1 env gene, sampled from 35 countries and tested: I) the random (neutral) distribution of the number of nucleotide changes; II) the proportion of bases at molecular equilibrium; III) the neutral expected homogeneity of the distribution of new fixated bases; IV) the hypothesis of the neighbor influence on the mutation rates in a site. The expected random number of fixations per site was estimated by Bose-Einstein statistics, and the expected frequencies of bases by matrices of mutation-fixation rates. The homogeneity of new fixations was analyzed using χ² and trinomial tests for homogeneity. Fixations of the central base in trinucleotides were used to test the neighbor influence on base substitutions. Neither the number of fixations nor the frequencies of bases fitted the expected neutral distribution. There was a highly significant heterogeneity in the distribution of new fixations, and several sites showed more transversions than transitions, showing that each nucleotide site has its own pattern of change. These three independent results make the neutral theory, the nearly neutral and the neighbor influence hypotheses untenable and indicate that evolution of env is rather highly selective.
我们对来自 35 个国家的 103 个 HIV-1 env 基因的核苷酸序列进行了研究：I）随机（中性）分布的核苷酸变化数量；II）分子平衡的碱基比例；III）新固定碱基分布的中性预期同质性；IV）位点突变率对邻居影响的假设。通过玻色-爱因斯坦统计估计每个位点预期的随机固定数量，通过突变-固定率矩阵估计碱基的预期频率。使用 χ² 和三项式检验来分析新固定的同质性。使用三核苷酸中中央碱基的固定来检验碱基取代对邻居的影响。固定的数量和碱基的频率都不符合预期的中性分布。新固定的分布存在高度显著的异质性，并且有几个位点的颠换多于转换，表明每个核苷酸位点都有其自身的变化模式。这三个独立的结果使得中性理论、近中性理论和邻居影响假说站不住脚，并表明 env 的进化是相当高选择性的。
