Quantifying Differences in the Tempo of Human Immunodeficiency Virus Type 1 Subtype Evolution

Abstract

Human immunodeficiency virus type 1 (HIV-1) genetic diversity, due to its high evolutionary rate, has long been identified as a main cause of problems in the development of an efficient HIV-1 vaccine. However, little is known about differences in evolutionary rate between different subtypes. In this study, we collected representative samples of the main epidemic subtypes and circulating recombinant forms (CRFs), namely, subsubtype A1, subtypes B, C, D, and G, and CRFs 01_AE and 02_AG. We analyzed separate data sets for pol and env. We performed a Bayesian Markov chain Monte Carlo relaxed-clock phylogenetic analysis and applied a codon model to the resulting phylogenetic trees to estimate nonsynonymous (dN) and synonymous (dS) rates along each and every branch. We found important differences in the evolutionary rates of the different subtypes. These are due to differences not only in the dN rate but also in the dS rate, varying in roughly similar ways, indicating that these differences are caused by both different selective pressures (for dN rate) and the replication dynamics (for dS rate) (i.e., mutation rate or generation time) of the strains. CRF02_AG and subtype G had higher rates, while subtype D had lower dN and dS rates than the other subtypes. The dN/dS ratio estimates were also different, especially for the env gene, with subtype G showing the lowest dN/dS ratio of all subtypes.

Molecular epidemiology of HIV-1 in Iceland: Early introductions, transmission dynamics and recent outbreaks among injection drug users

“…The first introduction was dated to 1978 which is one of the earliest estimates in Europe (Hue et al, 2005;Tebit and Arts, 2011). Our dating is plausible since it represents a date nine years after the estimated introduction of HIV-1 in the USA and was further supported by our evolutionary rate estimate since it was within the range of previously reported rates of the polymerase gene region in subtype B (Abecasis et al, 2009;Gilbert et al, 2007;Hue et al, 2005). HET has remained low since the first recorded case in Iceland, the proportion of HET in transmission clusters was found to be higher than MSM over time.…”

Emergence in Japan of an HIV-1 Variant Associated with Transmission among Men Who Have Sex with Men (MSM) in China: First Indication of the International Dissemination of the Chinese MSM Lineage

“…The estimated evolutionary rates were 2.81 (95% HPD, 2.42 to 3.22) ϫ 10 Ϫ3 and 1.81 (1.46 to 2.15) ϫ 10 Ϫ3 substitutions/site/year for CRF01_AE and subtype B, respectively. The results were essentially similar to those previously estimates for CRF01_AE and subtype B (31,36,37).…”

HIV Type 1 Transmission Networks Among Men Having Sex with Men and Heterosexuals in Kenya

“…36 We used a previously published normal prior to the time of the most recent common ancestor (tMRCA) of subtype A1 (1,954.2), with 95% Bayesian credible intervals (1,939.7-1,967.7). 37 Analyses of 250 million MCMC generations were performed in duplicate. Evolutionary parameters were sampled every 50,000 generations and a total of 5,000 posterior trees were retrieved.…”