Anderson J P, Rodrigo A G, Learn G H, Madan A, Delahunty C, Coon M, Girard M, Osmanov S, Hood L, Mullins J I
Departments of Molecular Biotechnology, Health Sciences Center, University of Washington, Seattle, Washington 98195, USA.
J Virol. 2000 Nov;74(22):10752-65. doi: 10.1128/jvi.74.22.10752-10765.2000.
The human immunodeficiency virus type 1 (HIV-1) epidemic in Southeast Asia has been largely due to the emergence of clade E (HIV-1E). It has been suggested that HIV-1E is derived from a recombinant lineage of subtype A (HIV-1A) and subtype E, with multiple breakpoints along the E genome. We obtained complete genome sequences of clade E viruses from Thailand (93TH057 and 93TH065) and from the Central African Republic (90CF11697 and 90CF4071), increasing the total number of HIV-1E complete genome sequences available to seven. Phylogenetic analysis of complete genomes showed that subtypes A and E are themselves monophyletic, although together they also form a larger monophyletic group. The apparent phylogenetic incongruence at different regions of the genome that was previously taken as evidence of recombination is shown to be not statistically significant. Furthermore, simulations indicate that bootscanning and pairwise distance results, previously used as evidence for recombination, can be misleading, particularly when there are differences in substitution or evolutionary rates across the genomes of different subtypes. Taken jointly, our analyses suggest that there is inadequate support for the hypothesis that subtype E variants are derived from a recombinant lineage. In contrast, many other HIV strains claimed to have a recombinant origin, including viruses for which only a single parental strain was employed for analysis, do indeed satisfy the statistical criteria we propose. Thus, while intersubtype recombinant HIV strains are indeed circulating, the criteria for assigning a recombinant origin to viral structures should include statistical testing of alternative hypotheses to avoid inappropriate assignments that would obscure the true evolutionary properties of these viruses.
东南亚的1型人类免疫缺陷病毒(HIV-1)流行很大程度上归因于E亚型(HIV-1E)的出现。有人提出,HIV-1E源自A亚型(HIV-1A)和E亚型的重组谱系,在E基因组上有多个断点。我们获得了来自泰国(93TH057和93TH065)以及中非共和国(90CF11697和90CF4071)的E亚型病毒的完整基因组序列,使可用的HIV-1E完整基因组序列总数增加到7个。完整基因组的系统发育分析表明,A亚型和E亚型本身是单系的,尽管它们共同也形成了一个更大的单系群体。先前被视为重组证据的基因组不同区域明显的系统发育不一致性在统计学上并不显著。此外,模拟表明,先前用作重组证据的引导扫描和成对距离结果可能会产生误导,特别是当不同亚型基因组的替换率或进化速率存在差异时。综合来看,我们的分析表明,E亚型变体源自重组谱系这一假设缺乏充分支持。相比之下,许多其他声称具有重组起源的HIV毒株,包括那些仅使用单一亲本毒株进行分析的病毒,确实满足我们提出的统计标准。因此,虽然亚型间重组的HIV毒株确实在传播,但为病毒结构指定重组起源的标准应包括对替代假设的统计检验,以避免不恰当的指定,从而掩盖这些病毒的真实进化特性。