Evidence for a recombinant origin of HIV-1 Group M from genomic variation

Abstract

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.

Revisiting the recombinant history of HIV-1 group M with dynamic network community detection

“…Moreover, a new non-recombinant HIV-1/M subtype L was proposed almost 30 years after the genomes were first sampled in 1983 and 1990 in what is now the Democratic Republic of the Congo [62]. Our analysis indicates that many of the HIV-1/M subtype reference genomes are actually recom-binant, which is consistent with previous work [18,19]. These findings support the idea that the current HIV-1 nomenclature [7], which has served as an important framework for our understanding of HIV-1 diversity and evolution, should be revisited in light of new genomic evidence.…”

“…A total of n = 3, 900 near full length (>8,000 nt) HIV-1/M genomes, manually curated from our previous study [18] were used in this study. Briefly, we constructed a reduced multiple sequence alignment based on the pairwise alignment of sequences against a consensus genome sequence, discarding insertions relative to this reference to filter out regions of relatively low evolutionary homology.…”

“…For instance, molecular clock estimates of the origin of the HIV-1 pandemic [17], or the time to the most recent ancestor (tMRCA), may be inaccurate due to a deep recombinant history, such that a single phylogenetic tree is not an adequate representation of discordant evolutionary histories relating different regions of the virus genome. In previous work [18], we used a sliding-window molecular clock analysis of near full-length HIV-1 genomes to show that different regions of the virus genome yield significantly different estimates of the tMRCA. This result supports the hypothesis that HIV-1 group M (HIV-1/M) may have a deep recombinant origin that involved at least two genome fragments with different evolutionary histories.…”

TickSialoFam (TSFam): A Database That Helps to Classify Tick Salivary Proteins, a Review on Tick Salivary Protein Function and Evolution, With Considerations on the Tick Sialome Switching Phenomenon

“…It is to be noted that the occurrence of recombination breakpoints could lead to false predictions of positive selected sites (Posada and Crandall, 2002;Bay and Bielawski, 2011). While positive selection is associated with fast gene evolution and divergence, intragenic recombination can strongly contribute to genome diversity among individuals, a situation that might be occurring within the lipocalin and DAP36 coding genes (Lauer et al, 2018;Olabode et al, 2019;Salim et al, 2019). As a note of caution, it should be considered that the diversity of transcripts from these multi-gene families could be artifactual due to the "de novo" assembly from small reads which could create false recombinant assemblies (Salmon et al, 2010).…”

Phylogenetic measures of indel rate variation among the HIV-1 group M subtypes

“…To estimate indel rates, we needed to accurately rescale the HIV-1 phylogenies in chronological time. Estimates of the tMRCA can vary by genomic region, and estimates from regions within the HIV-1 gag and pol genes tend to be more recent than regions in env irrespective of subtype (Olabode et al 2018). Overall, we determined that the diversity of HIV-1 sequences and sample collection dates were sufficient to fit a strict molecular clock model (Table 1).…”