Virus Evolution最新文献

Modern phylogenetics research is often performed within a Bayesian framework, using sampling algorithms such as Markov chain Monte Carlo (MCMC) to approximate the posterior distribution. These algorithms require careful evaluation of the quality of the generated samples. Within the field of phylogenetics, one frequently adopted diagnostic approach is to evaluate the effective sample size and to investigate trace graphs of the sampled parameters. A major limitation of these approaches is that they are developed for continuous parameters and therefore incompatible with a crucial parameter in these inferences: the tree topology. Several recent advancements have aimed at extending these diagnostics to topological space. In this reflection paper, we present two case studies-one on Ebola virus and one on HIV-illustrating how these topological diagnostics can contain information not found in standard diagnostics, and how decisions regarding which of these diagnostics to compute can impact inferences regarding MCMC convergence and mixing. Our results show the importance of running multiple replicate analyses and of carefully assessing topological convergence using the output of these replicate analyses. To this end, we illustrate different ways of assessing and visualizing the topological convergence of these replicates. Given the major importance of detecting convergence and mixing issues in Bayesian phylogenetic analyses, the lack of a unified approach to this problem warrants further action, especially now that additional tools are becoming available to researchers.

While influenza A virus (IAV) antigenic drift has been documented globally, in experimental animal infections, and in immunocompromised hosts, positive selection has generally not been detected in acute infections. This is likely due to challenges in distinguishing selected rare mutations from sequencing error, a reliance on cross-sectional sampling, and/or the lack of formal tests of selection for individual sites. Here, we sequenced IAV populations from 346 serial, daily nasal swabs from 143 individuals collected over three influenza seasons in a household cohort. Viruses were sequenced in duplicate, and intrahost single nucleotide variants (iSNVs) were identified at a 0.5% frequency threshold. Within-host populations exhibited low diversity, with >75% mutations present at <2% frequency. Children (0-5 years) had marginally higher within-host evolutionary rates than adolescents (6-18 years) and adults (>18 years, 4.4 × 10^-6 vs. 9.42 × 10^-7 and 3.45 × 10^-6, P < .001). Forty-five iSNVs had evidence of parallel evolution but were not over-represented in HA and NA. Several increased from minority to consensus level, with strong linkage among iSNVs across segments. A Wright-Fisher approximate Bayesian computational model identified positive selection at 23/256 loci (9%) in A(H3N2) specimens and 19/176 loci (11%) in A(H1N1)pdm09 specimens, and these were infrequently found in circulation. Overall, we found that within-host IAV populations were subject to genetic drift and purifying selection, with only subtle differences across seasons, subtypes, and age strata. Positive selection was rare and inconsistently detected.

Horizontal gene transfer events between viruses and hosts are widespread across the virosphere. In cyanophage-host systems, such events often involve the transfer of genes involved in photosynthetic processes. The genome of the lytic cyanophage Ma-LMM01 infecting the toxic, bloom-forming, freshwater Microcystis aeruginosa NIES-298 contains a homolog of the non-bleaching A (nblA) gene, which was probably transferred from a cyanobacterial host. The function of the NblA protein is to disassemble phycobilisomes, cyanobacterial light-harvesting complexes that can comprise up to half of the cellular soluble protein content. NblA thus plays an essential dual role in cyanobacteria: it protects the cell from high-light intensities and increases the intracellular nitrogen pool under nutrient limitation. NblA has previously been shown to interact with phycocyanin, one of the main components of phycobilisomes. Using structural modeling and protein-protein docking, we show that the NblA dimer of Ma-LMM01 is predicted to have a significantly higher binding affinity for M. aeruginosa NIES-298 phycocyanin (αβ)₆ hexamers, compared to the host homolog. Protein-protein docking suggests that the viral NblA structural model is able to bind deeper into the phycocyanin groove. The main structural difference between the virus and host NblA appears to be an additional α-helix near the N-terminus of the viral NblA, which interacts with the inside of the phycocyanin groove and could thus be considered partly responsible for this deeper binding. Interestingly, phylogenetic analyses indicate that this longer nblA was probably acquired from a different Microcystis host. Based on infection experiments and previous findings, we propose that a higher binding affinity of the viral NblA to the host phycocyanin may represent a selective advantage for the virus, whose infection cycle requires an increased phycobilisome degradation rate that is not fulfilled by the NblA of the host.

Viruses evolve by periods of relative stasis interleaved with sudden, rapid series of mutation fixations, known as evolutionary bursts. These bursts can be triggered by external factors, such as environmental changes, antiviral therapies, or spill-overs from reservoirs into novel host species. However, it has also been suggested that bursts may result from the intrinsic evolutionary dynamics of viruses. Indeed, bursts could be caused by fitness valley crossing, or a neutral exploration of a fitness plateau until an escape mutant is found. In order to investigate the importance of these intrinsic causes of evolutionary bursts, we used a simulation software package to perform massive evolution experiments of viral-like genomes. We tested two conditions: (i) after an external change and (ii) in a constant environment, with the latter condition guaranteeing the absence of an external triggering factor. As expected, an external change was almost systematically followed by an evolutionary burst. However, we also observed bursts in the constant environment as well, albeit much less frequently. We analyzed how many of these bursts are triggered by deleterious, quasi-neutral, or beneficial mutations and show that, while bursts can occasionally be triggered by valley crossing or traveling along neutral ridges, many of them were triggered by chromosomal rearrangements and, in particular, segmental duplications. Our results suggest that combinatorial differences between the different mutation types lead to punctuated evolutionary dynamics, with long periods of stasis occasionally interrupted by short periods of rapid evolution, akin to what is observed in virus evolution.