Genealogical evidence for positive selection in the <i>nef</i> gene of HIV-1

作     者：Zanotto, PMD Kallas, EG de Souza, RF Holmes, EC 

作者机构：Univ Sao Paulo Escola Paulista Med Bioinformat & Retrovirol Lab BR-05508900 Sao Paulo Brazil Univ Sao Paulo Escola Paulista Med Immunol Lab DIPA BR-05508900 Sao Paulo Brazil Univ Oxford Dept Zool Wellcome Trust Ctr Epidemiol Infect Dis Oxford OX1 3PS England 

出 版 物：《GENETICS》 (遗传学)

年 卷 期：1999年第153卷第3期

页      面：1077-1089页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 09[农学] 

主　　题：获得性免疫缺陷综合征/病因学 获得性免疫缺陷综合征/病毒学 等位基因 氨基酸序列 密码子 进化 分子 基因产物 nef/化学 基因产物 nef/遗传学 基因 nef HIV-1/遗传学 血友病A/并发症 似然函数 分子序列数据 种系发生 选择(遗传学) 序列比对 序列同源性 氨基酸 人类 

摘      要：The pattern and process of evolution in the nef gene of HIV-1 was analyzed within and among patients. Using a maximum likelihood method that allows for variable intensity of selection pressure among codons, strong positive selection was detected in a hemophiliac patient over 30 mo of infection. By reconstructing the process of allele substitution in this patient using parsimony, the synapomorphic amino acid changes separating each time point were found to have high probabilities of being under positive selection, with selective coefficients of at least 3.6%. Positive selection was also detected among 39 nef sequences from HIV-1 subtype B. Tn contrast, multiple pairwise comparisons of nonsynonymous and synonymous substitution rates provided no good evidence for positive selection and sliding window analyses failed to detect most positively selected sites. These findings demonstrate that positive selection is an important determinant of nef gene evolution and that genealogy-based methods outperform pairwise methods in the detection of adaptive evolution. Mapping the locations of positively selected sites may also be of use in identifying targets of the immune response and hence aid vaccine design.