Virus Evolution最新文献

{"title":"Enhanced detection and molecular modeling of adaptive mutations in SARS-CoV-2 coding and non-coding regions using the c/µ test.","authors":"Nicholas J Paradis, Chun Wu","doi":"10.1093/ve/veae089","DOIUrl":"10.1093/ve/veae089","url":null,"abstract":"<p><p>Accurately identifying mutations under beneficial selection in viral genomes is crucial for understanding their molecular evolution and pathogenicity. Traditional methods like the Ka/Ks test, which assesses non-synonymous (Ka) versus synonymous (Ks) substitution rates, assume that synonymous substitutions at synonymous sites are neutral and thus is equal to the mutation rate (µ). Yet, evidence suggests that synonymous sites in translated regions (TRs) and untranslated regions (UTRs) can be under strong beneficial selection (Ks > µ) and strongly conserved (Ks ≈ 0), leading to false predictions of adaptive mutations from codon-by-codon Ka/Ks analysis. Our previous work used a relative substitution rate test (c/µ, c: substitution rate in UTR/TR, and µ: mutation rate) to identify adaptive mutations in SARS-CoV-2 genome without the neutrality assumption of the synonymous sites. This study refines the c/µ test by optimizing µ value, leading to a smaller set of nucleotide and amino acid sites under beneficial selection in both UTR (11 sites with c/µ > 3) and TR (69 nonsynonymous sites: c/µ > 3 and Ka/Ks > 2.5; 107 synonymous sites: Ks/µ > 3). Encouragingly, the top two mutations in UTR and 70% of the top nonsynonymous mutations in TR had reported or predicted effects in the literature. Molecular modeling of top adaptive mutations for some critical proteins (S, NSP11, and NSP5) was carried out to elucidate the possible molecular mechanism of their adaptivity.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"10 1","pages":"veae089"},"PeriodicalIF":5.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11584280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A phylogenetics and variant calling pipeline to support SARS-CoV-2 genomic epidemiology in the UK.","authors":"Rachel Colquhoun, Áine O'Toole, Verity Hill, J T McCrone, Xiaoyu Yu, Samuel M Nicholls, Radoslaw Poplawski, Thomas Whalley, Natalie Groves, Nicholas Ellaby, Nick Loman, Tom Connor, Andrew Rambaut","doi":"10.1093/ve/veae083","DOIUrl":"10.1093/ve/veae083","url":null,"abstract":"<p><p>In response to the escalating SARS-CoV-2 pandemic, in March 2020 the COVID-19 Genomics UK (COG-UK) consortium was established to enable national-scale genomic surveillance in the UK. By the end of 2020, 49% of all SARS-CoV-2 genome sequences globally had been generated as part of the COG-UK programme, and to date, this system has generated >3 million SARS-CoV-2 genomes. Rapidly and reliably analysing this unprecedented number of genomes was an enormous challenge. To fulfil this need and to inform public health decision-making, we developed a centralized pipeline that performs quality control, alignment, and variant calling and provides the global phylogenetic context of sequences. We present this pipeline and describe how we tailored it as the pandemic progressed to scale with the increasing amounts of data and to provide the most relevant analyses on a daily basis.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"10 1","pages":"veae083"},"PeriodicalIF":5.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic epidemiology reveals the variation and transmission properties of SARS-CoV-2 in a single-source community outbreak.","authors":"Ning Zhao, Min He, HengXue Wang, LiGuo Zhu, Nan Wang, Wei Yong, HuaFeng Fan, SongNing Ding, Tao Ma, Zhong Zhang, XiaoXiao Dong, ZiYu Wang, XiaoQing Dong, XiaoYu Min, HongBo Zhang, Jie Ding","doi":"10.1093/ve/veae085","DOIUrl":"10.1093/ve/veae085","url":null,"abstract":"<p><p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the coronavirus disease 2019 (COVID-19) pandemic, which is still a global public health concern. During March 2022, a rapid and confined single-source outbreak of SARS-CoV-2 was identified in a community in Nanjing municipal city. Overall, 95 individuals had laboratory-confirmed SARS-CoV-2 infection. The whole genomes of 61 viral samples were obtained, which were all members of the BA.2.2 lineage and clearly demonstrated the presence of one large clade, and all the infections could be traced back to the original index case. The most distant sequence from the index case presented a difference of 4 SNPs, and 118 intrahost single-nucleotide variants (iSNVs) at 74 genomic sites were identified. Some minor iSNVs can be transmitted and subsequently rapidly fixed in the viral population. The minor iSNVs transmission resulted in at least two nucleotide substitutions among all seven SNPs identified in the outbreak, generating genetically diverse populations. We estimated the overall transmission bottleneck size to be 3 using 11 convincing donor-recipient transmission pairs. Our study provides new insights into genomic epidemiology and viral transmission, revealing how iSNVs become fixed in local clusters, followed by viral transmission across the community, which contributes to population diversity.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"10 1","pages":"veae085"},"PeriodicalIF":5.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-read transcriptomics of Ostreid herpesvirus 1 uncovers a conserved expression strategy for the capsid maturation module and pinpoints a mechanism for evasion of the ADAR-based antiviral defence.","authors":"Umberto Rosani, Enrico Bortoletto, Xiang Zhang, Bo-Wen Huang, Lu-Sheng Xin, Mart Krupovic, Chang-Ming Bai","doi":"10.1093/ve/veae088","DOIUrl":"10.1093/ve/veae088","url":null,"abstract":"<p><p>Ostreid herpesvirus 1 (OsHV-1), a member of the family <i>Malacoherpesviridae</i> (order <i>Herpesvirales</i>), is a major pathogen of bivalves. However, the molecular details of the malacoherpesvirus infection cycle and its overall similarity to the replication of mammalian herpesviruses (family <i>Orthoherpesviridae</i>) remain obscure. Here, to gain insights into the OsHV-1 biology, we performed long-read sequencing of infected blood clams, <i>Anadara broughtonii</i>, which yielded over one million OsHV-1 long reads. These data enabled the annotation of the viral genome with 78 gene units and 274 transcripts, of which 67 were polycistronic mRNAs, 35 ncRNAs, and 20 natural antisense transcripts (NATs). Transcriptomics and proteomics data indicate preferential transcription and independent translation of the capsid scaffold protein as an OsHV-1 capsid maturation protease isoform. The conservation of this transcriptional architecture across <i>Herpesvirales</i> likely indicates its functional importance and ancient origin. Moreover, we traced RNA editing events using short-read sequencing and supported the presence of inosine nucleotides in native OsHV-1 RNA, consistent with the activity of adenosine deaminase acting on dsRNA 1 (ADAR1). Our data suggest that, whereas RNA hyper-editing is concentrated in specific regions of the OsHV-1 genome, single-nucleotide editing is more dispersed along the OsHV-1 transcripts. In conclusion, we reveal the existence of conserved pan-<i>Herpesvirales</i> transcriptomic architecture of the capsid maturation module and uncover a transcription-based viral counter defence mechanism, which presumably facilitates the evasion of the host ADAR antiviral system.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"10 1","pages":"veae088"},"PeriodicalIF":5.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11565193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolution of virulence in emerging epidemics: from theory to experimental evolution and back.","authors":"Wakinyan Benhamou, François Blanquart, Marc Choisy, Thomas W Berngruber, Rémi Choquet, Sylvain Gandon","doi":"10.1093/ve/veae069","DOIUrl":"10.1093/ve/veae069","url":null,"abstract":"<p><p>The experimental validation of theoretical predictions is a crucial step in demonstrating the predictive power of a model. While quantitative validations are common in infectious diseases epidemiology, experimental microbiology primarily focuses on the evaluation of a qualitative match between model predictions and experiments. In this study, we develop a method to deepen the quantitative validation process with a polymorphic viral population. We analyse the data from an experiment carried out to monitor the evolution of the temperate bacteriophage <i>λ</i> spreading in continuous cultures of <i>Escherichia coli</i>. This experimental work confirmed the influence of the epidemiological dynamics on the evolution of transmission and virulence of the virus. A variant with larger propensity to lyse bacterial cells was favoured in emerging epidemics (when the density of susceptible cells was large), but counter-selected when most cells were infected. Although this approach qualitatively validated an important theoretical prediction, no attempt was made to fit the model to the data nor to further develop the model to improve the goodness of fit. Here, we show how theoretical analysis-including calculations of the selection gradients-and model fitting can be used to estimate key parameters of the phage life cycle and yield new insights on the evolutionary epidemiology of the phage <i>λ</i>. First, we show that modelling explicitly the infected bacterial cells which will eventually be lysed improves the fit of the transient dynamics of the model to the data. Second, we carry out a theoretical analysis that yields useful approximations that capture at the onset and at the end of an epidemic the effects of epidemiological dynamics on selection and differentiation across distinct life stages of the virus. Finally, we estimate key phenotypic traits characterizing the two strains of the virus used in our experiment such as the rates of prophage reactivation or the probabilities of lysogenization. This study illustrates the synergy between experimental, theoretical, and statistical approaches; and especially how interpreting the temporal variation in the selection gradient and the differentiation across distinct life stages of a novel variant is a powerful tool to elucidate the evolutionary epidemiology of emerging infectious diseases.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"10 1","pages":"veae069"},"PeriodicalIF":5.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On the importance of assessing topological convergence in Bayesian phylogenetic inference.","authors":"Marius Brusselmans, Luiz Max Carvalho, Samuel L Hong, Jiansi Gao, Frederick A Matsen Iv, Andrew Rambaut, Philippe Lemey, Marc A Suchard, Gytis Dudas, Guy Baele","doi":"10.1093/ve/veae081","DOIUrl":"10.1093/ve/veae081","url":null,"abstract":"<p><p>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 <i>effective sample size</i> 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 <i>tree topology</i>. 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.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"10 1","pages":"veae081"},"PeriodicalIF":5.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11556345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influenza A virus within-host evolution and positive selection in a densely sampled household cohort over three seasons.","authors":"Emily E Bendall, Yuwei Zhu, William J Fitzsimmons, Melissa Rolfes, Alexandra Mellis, Natasha Halasa, Emily T Martin, Carlos G Grijalva, H Keipp Talbot, Adam S Lauring","doi":"10.1093/ve/veae084","DOIUrl":"10.1093/ve/veae084","url":null,"abstract":"<p><p>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, <i>P</i> < .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.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"10 1","pages":"veae084"},"PeriodicalIF":5.5,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11498174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural models predict a significantly higher binding affinity between the NblA protein of cyanophage Ma-LMM01 and the phycocyanin of <i>Microcystis aeruginosa</i> NIES-298 compared to the host homolog.","authors":"Isaac Meza-Padilla, Brendan J McConkey, Jozef I Nissimov","doi":"10.1093/ve/veae082","DOIUrl":"https://doi.org/10.1093/ve/veae082","url":null,"abstract":"<p><p>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 <i>Microcystis aeruginosa</i> NIES-298 contains a homolog of the <i>non-bleaching A</i> (<i>nblA</i>) 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 <i>M. aeruginosa</i> 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 <i>nblA</i> was probably acquired from a different <i>Microcystis</i> 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.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"10 1","pages":"veae082"},"PeriodicalIF":5.5,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11477984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142481730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovation in viruses: fitness valley crossing, neutral landscapes, or just duplications?","authors":"Paul Banse, Santiago F Elena, Guillaume Beslon","doi":"10.1093/ve/veae078","DOIUrl":"10.1093/ve/veae078","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"10 1","pages":"veae078"},"PeriodicalIF":5.5,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11463231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Independent repeated mutations within the alphaviruses Ross River virus and Barmah Forest virus indicates convergent evolution and past positive selection in ancestral populations despite ongoing purifying selection","authors":"Alyssa T Pyke, Daniel J Wilson, Alice Michie, John S Mackenzie, Allison Imrie, Jane Cameron, Stephen L Doggett, John Haniotis, Lara J Herrero, Leon Caly, Stacey E Lynch, Peter T Mee, Eugene T Madzokere, Ana L Ramirez, Devina Paramitha, Jody Hobson-Peters, David W Smith, Richard Weir, Mitchell Sullivan, Julian Druce, Lorna Melville, Jennifer Robson, Robert Gibb, Andrew F van den Hurk, Sebastian Duchene","doi":"10.1093/ve/veae080","DOIUrl":"https://doi.org/10.1093/ve/veae080","url":null,"abstract":"Ross River virus (RRV) and Barmah Forest virus (BFV) are arthritogenic arthropod-borne viruses (arboviruses) that exhibit generalist host associations and share distributions in Australia and Papua New Guinea (PNG). Using stochastic mapping and discrete-trait phylogenetic analyses we profiled the independent evolution of RRV and BFV signature mutations. Analysis of 186 RRV and 88 BFV genomes demonstrated their viral evolution trajectories have involved repeated selection of mutations, particularly in the nonstructural protein 1 (nsP1) and envelope 3 (E3) genes suggesting convergent evolution. Convergent mutations in the nsP1 genes of RRV (residues 248 and 441) and BFV (residues 297 and 447) may be involved with catalytic enzyme mechanisms and host membrane interactions during viral RNA replication and capping. Convergent E3 mutations (RRV site 59 and BFV site 57) may be associated with enzymatic furin activity and cleavage of E3 from protein precursors assisting viral maturation and infectivity. Given their requirement to replicate in disparate insect and vertebrate hosts, convergent evolution in RRV and BFV may represent a dynamic link between their requirement to selectively ‘fine-tune’ intracellular host interactions and viral replicative enzymatic processes. Despite evidence of evolutionary convergence, selection pressure analyses did not reveal any RRV or BFV amino acid sites under strong positive selection and only weak positive selection for nonstructural protein sites. These findings may indicate that their alphavirus ancestors were subject to positive selection events which predisposed ongoing pervasive convergent evolution, and this largely supports continued purifying selection in RRV and BFV populations during their replication in mosquito and vertebrate hosts.","PeriodicalId":56026,"journal":{"name":"Virus Evolution","volume":"78 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}