Hughes Austin L, Hughes Mary Ann K, Friedman Robert
Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA.
Virus Res. 2007 Feb;123(2):147-53. doi: 10.1016/j.virusres.2006.08.012. Epub 2006 Sep 26.
In an analysis of the patterns of nucleotide diversity in 26 datasets providing population-level data on different genomic regions of different hepatitis C virus (HCV) subtypes, known cytotoxic T-lymphocyte (CTL) epitope regions in most cases showed evidence of the occurrence of purifying selection. Two main factors were found to be associated with the strength of purifying selection: (1) purifying selection was stronger in CTL epitopes in non-envelope proteins than in envelope proteins and (2) purifying selection was stronger when the epitope was "matched", i.e., when the described or "canonical" epitope sequence was present unaltered in at least one sequence in the dataset. Of all polymorphic sites, non-synonymous sites in matched CTL epitopes in non-envelope proteins had the lowest gene diversities, implying that these variants are subject to ongoing purifying selection. This in turn suggests that the population frequency of such variants may of be the result of a balance between opposing forces: on the one hand, positive selection favoring escape mutants in hosts that express the presenting MHC molecule and, on the other hand, purifying selection acting, in the absence of the presenting MHC molecule, to reduce the frequency of slightly deleterious variants.
在一项对26个数据集的核苷酸多样性模式分析中，这些数据集提供了不同丙型肝炎病毒（HCV）亚型不同基因组区域的群体水平数据，在大多数情况下，已知的细胞毒性T淋巴细胞（CTL）表位区域显示出纯化选择发生的证据。发现有两个主要因素与纯化选择的强度相关：（1）非包膜蛋白中的CTL表位的纯化选择比包膜蛋白中的更强；（2）当表位“匹配”时，即当所述的或“典型”表位序列在数据集中的至少一个序列中未改变地存在时，纯化选择更强。在所有多态性位点中，非包膜蛋白中匹配的CTL表位中的非同义位点具有最低的基因多样性，这意味着这些变体正在经历纯化选择。这反过来表明，此类变体的群体频率可能是两种相反力量之间平衡的结果：一方面，正向选择有利于表达呈递MHC分子的宿主中的逃逸突变体；另一方面，在不存在呈递MHC分子的情况下，纯化选择起作用以降低轻微有害变体的频率。
