Olabode Abayomi S, Avino Mariano, Ng Garway T, Abu-Sardanah Faisal, Dick David W, Poon Art F Y
Department of Pathology & Laboratory Medicine, Western University, London, Ontario, Canada.
Department of Applied Mathematics, Western University, London, Ontario, Canada.
Virus Evol. 2019 Jan 22;5(1):vey039. doi: 10.1093/ve/vey039. eCollection 2019 Jan.
Reconstructing the early dynamics of the HIV-1 pandemic can provide crucial insights into the socioeconomic drivers of emerging infectious diseases in human populations, including the roles of urbanization and transportation networks. Current evidence indicates that the global pandemic comprising almost entirely of HIV-1/M originated around the 1920s in central Africa. However, these estimates are based on molecular clock estimates that are assumed to apply uniformly across the virus genome. There is growing evidence that recombination has played a significant role in the early history of the HIV-1 pandemic, such that different regions of the HIV-1 genome have different evolutionary histories. In this study, we have conducted a dated-tip analysis of all near full-length HIV-1/M genome sequences that were published in the GenBank database. We used a sliding window approach similar to the 'bootscanning' method for detecting breakpoints in inter-subtype recombinant sequences. We found evidence of substantial variation in estimated root dates among windows, with an estimated mean time to the most recent common ancestor of 1922. Estimates were significantly autocorrelated, which was more consistent with an early recombination event than with stochastic error variation in phylogenetic reconstruction and dating analyses. A piecewise regression analysis supported the existence of at least one recombination breakpoint in the HIV-1/M genome with interval-specific means around 1929 and 1913, respectively. This analysis demonstrates that a sliding window approach can accommodate early recombination events outside the established nomenclature of HIV-1/M subtypes, although it is difficult to incorporate the earliest available samples due to their limited genome coverage.
重建HIV-1大流行的早期动态可以为了解人类群体中新发传染病的社会经济驱动因素提供关键见解,包括城市化和交通网络的作用。目前的证据表明,几乎完全由HIV-1/M组成的全球大流行起源于20世纪20年代左右的中非。然而,这些估计是基于分子钟估计,假定其在病毒基因组中均匀适用。越来越多的证据表明,重组在HIV-1大流行的早期历史中发挥了重要作用,以至于HIV-1基因组的不同区域有不同的进化历史。在本研究中,我们对GenBank数据库中公布的所有近乎全长的HIV-1/M基因组序列进行了定年末端分析。我们使用了一种类似于“bootscanning”方法的滑动窗口方法来检测亚型间重组序列中的断点。我们发现各窗口估计的根日期存在显著差异,估计的最近共同祖先的平均时间为1922年。估计值存在显著的自相关性,这与早期重组事件比与系统发育重建和定年分析中的随机误差变异更一致。分段回归分析支持HIV-1/M基因组中至少存在一个重组断点,区间特异性均值分别约为1929年和1913年。该分析表明,滑动窗口方法可以适应HIV-1/M亚型既定命名之外的早期重组事件,尽管由于最早可用样本的基因组覆盖有限,难以纳入这些样本。