pangolin lineage covid

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5. Because the SARS-CoV-2 S protein has been implicated in past recombination events or possibly convergent evolution12, we specifically investigated several subregions of the Sproteinthe N-terminal domain of S1, the C-terminal domain of S1, the variable-loop region of the C-terminal domain, and S2. 35, 247251 (2018). Viral metagenomics revealed Sendai virus and coronavirus infection of Malayan pangolins (Manis javanica). Google Scholar. Aiewsakun, P. & Katzourakis, A. Time-dependent rate phenomenon in viruses. GARD identified eight breakpoints that were also within 50nt of those identified by 3SEQ. All sequence data analysed in this manuscript are available at https://github.com/plemey/SARSCoV2origins. We use three bioinformatic approaches to remove the effects of recombination, and we combine these approaches to identify putative non-recombinant regions that can be used for reliable phylogenetic reconstruction and dating. When viewing the last 7kb of the genome, a clade of viruses from northern China appears to cluster with sequences from southern Chinese provinces but, when inspecting trees from different parts of ORF1ab, the N. China clade is phylogenetically separated from the S. China clade. Share . Identification of diverse alphacoronaviruses and genomic characterization of a novel severe acute respiratory syndrome-like coronavirus from bats in China. Webster, R. G., Bean, W. J., Gorman, O. T., Chambers, T. M. & Kawaoka, Y. Evolution and ecology of influenza A viruses. To evaluate the performance procedure, we confirmed that the recombination masking resulted in (1) a markedly different outcome of the PHI test64, (2) removal of well-supported (bootstrap value >95%) incompatible splits in Neighbor-Net65 and (3) a near-complete reduction of mosaic signal as identified by 3SEQ. In March, when covid cases began spiking around India, Bani Jolly went hunting for answers in the virus's genetic code. This study provides an integration of existing classifications and describes evolutionary trends of the SARS-CoV . Trafficked pangolins can carry coronaviruses closely related to Maclean, O. Means and 95% HPD intervals are 0.080 [0.0580.101] and 0.530 [0.3040.780] for the patristic distances between SARS-CoV-2 and RaTG13 (green) and 0.143 [0.1090.180] and 0.154 [0.0930.231] for the patristic distances between SARS-CoV-2 and Pangolin 2019 (orange). Google Scholar. Because there is no single accepted method of inferring breakpoints and identifying clean subregions with high certainty, we implemented several approaches to identifying three classic statistical signals of recombination: mosaicism, phylogenetic incongruence and excessive homoplasy51. PLoS Pathog. Kosakovsky Pond, S. L., Posada, D., Gravenor, M. B., Woelk, C. H. & Frost, S. D. W. Automated phylogenetic detection of recombination using a genetic algorithm. and D.L.R. As of December 2, 2021, SJdRP, a medium-sized city in the Northwest region of So Paulo state, Brazil (Fig. This is not surprising for diverse viral populations with relatively deep evolutionary histories. Schierup, M. H. & Hein, J. Recombination and the molecular clock. Biol. Methods Ecol. Ge, X. et al. The existing diversity and dynamic process of recombination amongst lineages in the bat reservoir demonstrate how difficult it will be to identify viruses with potential to cause major human outbreaks before they emerge. We used an uncorrelated relaxed clock model with log-normal distribution for all datasets, except for the low-diversity SARS data for which we specified a strict molecular clock model. Robertson, D. nCoVs relationship to bat coronaviruses & recombination signals (no snakes) no evidence the 2019-nCoV lineage is recombinant. Holmes, E. C., Rambaut, A. Graham, R. L. & Baric, R. S. Recombination, reservoirs, and the modular spike: mechanisms of coronavirus cross-species transmission. 82, 18191826 (2008). 4). Of importance for future spillover events is the appreciation that SARS-CoV-2 has emerged from the same horseshoe bat subgenus that harbours SARS-like coronaviruses. An initial genomic sequence analysis found that the reemergence of COVID-19 in New Zealand was caused by a SARS-CoV-2 from the (now ancestral) lineage B.1.1.1 of the pangolin nomenclature ( 17 ). J. Virol. All four of these breakpoints were also identified with the tree-based recombination detection method GARD35. Virus Evol. Adv. PubMed Evol. The shaded region corresponds to the Sprotein. The genetic distances between SARS-CoV-2 and RaTG13 (bottom) demonstrate that their relationship is consistent across all regions except for the variable loop. Preprint at https://doi.org/10.1101/2020.05.28.122366 (2020). Use the Previous and Next buttons to navigate the slides or the slide controller buttons at the end to navigate through each slide. Menachery, V. D. et al. In the variable-loop region, RaTG13 diverges considerably with the TMRCA, now outside that of SARS-CoV-2 and the Pangolin Guangdong 2019 ancestor, suggesting that RaTG13 has acquired this region from a more divergent and undetected bat lineage. 2). Scientists defined the pangolin lineage of this variant to be B.1.1.523 and it was originally recognized as a variant under monitoring on July 14, 2021. Intragenomic rearrangements involving 5-untranslated region segments in SARS-CoV-2, other betacoronaviruses, and alphacoronaviruses, Crystal structure of the CoV-Y domain of SARS-CoV-2 nonstructural protein 3, Association of underlying comorbidities and progression of COVID-19 infection amongst 2586 patients hospitalised in the National Capital Region of India: a retrospective cohort study, Molecular characterization of horse nettle virus A, a new member of subgroup B of the genus Nepovirus, Molecular phylogeny of coronaviruses and host receptors among domestic and close-contact animals reveals subgenome-level conservation, crossover, and divergence. Pangolin was developed to implement the dynamic nomenclature of SARS-CoV-2 lineages, known as the Pango nomenclature. In case of DRAGEN COVID Lineage tool, the minimum accepted alignment score was set to 22 and results with scores <22 were discarded. Early detection via genomics was not possible during Southeast Asias initial outbreaks of avian influenza H5N1 (1997 and 20032004) or the first SARS outbreak (20022003). It is available as a command line tool and a web application. Bruen, T. C., Philippe, H. & Bryant, D. A simple and robust statistical test for detecting the presence of recombination. The S1 protein of Pangolin-CoV is much more closely related to SARS-CoV-2 than to RaTG13. Mol. While pangolins could be acting as intermediate hosts for bat viruses to get into humansthey develop severe respiratory disease38 and commonly come into contact with people through traffickingthere is no evidence that pangolin infection is a requirement for bat viruses to cross into humans. 6, e14 (2017). These rate priors are subsequently used in the Bayesian inference of posterior rates for NRR1, NRR2, and NRA3 as indicated by the solid arrows. Article Nature 583, 282285 (2020). 1 Phylogenetic relationships in the C-terminal domain (CTD). In our analyses of the sarbecovirus datasets, we incorporated the uncertainty of the sampling dates when exact dates were not available. M.F.B. eLife 7, e31257 (2018). Complete genome sequence data were downloaded from GenBank and ViPR; accession numbers of all 68sequences are available in Supplementary Table 4. Researchers have found that SARS-CoV-2 in humans shares about 90.3% of its genome sequence with a coronavirus found in pangolins (Cyranoski, 2020). We say that this approach is conservative because sequences and subregions generating recombination signals have been removed, and BFRs were concatenated only when no PI signals could be detected between them. performed recombination analysis for non-recombining regions1 and 2, breakpoint analysis and phylogenetic inference on recombinant segments. Consistent with this, we estimate a concomitantly decreasing non-synonymous-to-synonymous substitution rate ratio over longer evolutionary timescales: 1.41 (1.20,1.68), 0.35 (0.30,0.41) and 0.133 (0.129,0.136) for SARS, MERS-CoV and HCoV-OC43, respectively. Genetics 176, 10351047 (2007). Mol. EPI_ISL_410538, EPI_ISL_410539, EPI_ISL_410540, EPI_ISL_410541 and EPI_ISL_410542) for the use of sequence data via the GISAID platform. Furthermore, the other key feature thought to be instrumental in the ability of SARS-CoV-2 to infect humansa polybasic cleavage site insertion in the Sproteinhas not yet been seen in another close bat relative of the SARS-CoV-2 virus. Coronavirus Disease 2019 (COVID-19) Situation Report 51 (World Health Organization, 2020). Coronavirus: Pangolins found to carry related strains. However, inconsistency in the nomenclature limits uniformity in its epidemiological understanding. Accurate estimation of ages for deeper nodes would require adequate accommodation of time-dependent rate variation. This new approach classifies the newly sequenced genome against all the diverse lineages present instead of a representative select sequences. N. Engl. acknowledges support by the Research FoundationFlanders (Fonds voor Wetenschappelijk OnderzoekVlaanderen (nos. It compares the new genome against the large, diverse population of sequenced strains using a Bayesian evolutionary rate and divergence date estimates were shown to be consistent for these three approaches and for two different prior specifications of evolutionary rates based on HCoV-OC43 and MERS-CoV. J. Med Virol. Wong, A. C. P., Li, X., Lau, S. K. P. & Woo, P. C. Y. It is clear from our analysis that viruses closely related to SARS-CoV-2 have been circulating in horseshoe bats for many decades. In other words, a true breakpoint is less likely to be called as such (this is breakpoint-conservative), and thus the construction of a non-recombining region may contain true recombination breakpoints (with insufficient evidence to call them as such). stand-alone pangolin work flows or Illumina DRAGEN COVID Lineage App (v3.5.5) following the default parameters. The latter was reconstructed using IQTREE66 v.2.0 under a general time-reversible (GTR) model with a discrete gamma distribution to model inter-site rate variation. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Despite the SARS-CoV-2 lineages acquisition of residues in its Spike (S) proteins receptor-binding domain (RBD) permitting the use of human ACE2 (ref. Are pangolins the intermediate host of the 2019 novel coronavirus (SARS-CoV-2)? Phylogenies of subregions of NRR1 depict an appreciable degree of spatial structuring of the bat sarbecovirus population across different regions (Fig. Originally, PANGOLIN used a maximum-likelihood-based assignment algorithm to assign query SARS-CoV-2 the most likely lineage sequence. This is notable because the variable-loop region contains the six key contact residues in the RBD that give SARS-CoV-2 its ACE2-binding specificity27,37. Viruses 11, 174 (2019). PubMed Central To employ phylogenetic dating methods, recombinant regions of a 68-genome sarbecovirus alignment were removed with three independent methods. There are outstanding evolutionary questions on the recent emergence of human coronavirus SARS-CoV-2 including the role of reservoir species, the role of recombination and its time of divergence from animal viruses. While such models have recently been made available, we lack the information to calibrate the rate decline over time (for example, through internal node calibrations44). All custom code used in the manuscript is available at https://github.com/plemey/SARSCoV2origins. Humans' selfish, speciesist treatment of these animals could be the very reason why the novel coronavirus exists. Divergence time estimates based on the HCoV-OC43-centred rate prior for the separate BFRs (Supplementary Table 3) show consistency in TMRCA estimates across the genome. We showed that severe acute respiratory syndrome coronavirus 2 is probably a novel recombinant virus. The genetic distances between SARS-CoV-2 and Pangolin Guangdong 2019 are consistent across all regions except the N-terminal domain, implying that a recombination event between these two sequences in this region is unlikely. The web application was developed by the Centre for Genomic Pathogen Surveillance. Extensive diversity of coronaviruses in bats from China. Don't blame pangolins, coronavirus family tree tracing could prove key J. Virol. To estimate non-synonymous over synonymous rate ratios for the concatenated coding genes, we used the empirical Bayes Renaissance countingprocedure67. These differences reflect the fact that rate estimates can vary considerably with the timescale of measurement, a frequently observed phenomenon in viruses known as time-dependent evolutionary rates41,43,44. Suchard, M. A. et al. Mol. PLoS Pathog. Abstract. The 2009 influenza pandemic and subsequent outbreaks of MERS-CoV (2012), H7N9 avian influenza (2013), Ebola virus (2014) and Zika virus (2015) were met with rapid sequencing and genomic characterization. The Sichuan (SC2018) virus appears to be a recombinant of northern/central and southern viruses, while the two Zhejiang viruses (CoVZXC21 and CoVZC45) appear to carry a recombinant region from southern or central China. 32, 268274 (2014). Based on the identified breakpoints in each genome, only the major non-recombinant region is kept in each genome while other regions are masked. & Holmes, E. C. Recombination in evolutionary genomics. Slider with three articles shown per slide. The coverage threshold and consensus sequence generation threshold were set to 20 and 90 respectively. COVID-19 lineage names can be confusing to navigate; there are many aliases and if you want to catch them all to examine further in data analyses it helps to Allen O'Brien on LinkedIn: #r #rstudio #rstats #pangolin #covid19 #datascience #epidemiology If stopping an outbreak in its early stages is not possibleas was the case for the COVID-19 epidemic in Hubeiidentification of origins and point sources is nevertheless important for containment purposes in other provinces and prevention of future outbreaks. SARS-CoV-2 and RaTG13 are the most closely related (their most recent common ancestor nodes denoted by green circles), except in the 222-nt variable-loop region of the C-terminal domain (bar graphs at bottom). Eight other BFRs <500nt were identified, and the regions were named BFRAJ in order of length. A tag already exists with the provided branch name. Sarbecovirus, HCoV-OC43 and SARS-CoV data were assembled from GenBank to be as complete as possible, with sampling year as an inclusion criterion. D.L.R. 84, 31343146 (2010). Extended Data Fig. Sign up for the Nature Briefing newsletter what matters in science, free to your inbox daily. the development of viral diversity. CNN . While there is evidence of positive selection in the sarbecovirus lineage leading to RaTG13/SARS-CoV-2 (ref. Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage - Nature 2, bottom) show that SARS-CoV-2 is unlikely to have acquired the variable loop from an ancestor of Pangolin-2019 because these two sequences are approximately 1015% divergent throughout the entire Sprotein (excluding the N-terminal domain). Wang, H., Pipes, L. & Nielsen, R. Synonymous mutations and the molecular evolution of SARS-Cov-2 origins. Center for Infectious Disease Dynamics, Department of Biology, Pennsylvania State University, University Park, PA, USA, Department of Microbiology, Immunology and Transplantation, KU Leuven, Rega Institute, Leuven, Belgium, Department of Biological Sciences, Xian Jiaotong-Liverpool University, Suzhou, China, State Key Laboratory of Emerging Infectious Diseases, School of Public Health, The University of Hong Kong, Hong Kong SAR, China, Department of Biology, University of Texas Arlington, Arlington, TX, USA, Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, UK, MRC-University of Glasgow Centre for Virus Research, Glasgow, UK, You can also search for this author in 4. Centre for Genomic Pathogen Surveillance. and JavaScript. GitHub - cov-lineages/pangolin: Software package for assigning SARS-CoV-2 genome sequences to global lineages. performed codon usage analysis. In this approach, we considered a breakpoint as supported only if it had three types of statistical support: from (1) mosaic signals identified by 3SEQ, (2) PI signals identified by building trees around 3SEQs breakpoints and (3) the GARD algorithm35, which identifies breakpoints by identifying PI signals across proposed breakpoints. Scientists trying to trace the ancestry of SARS-CoV-2, the virus responsible for COVID-19, have found the pangolin is unlikely to be the source of the virus responsible for the current pandemic. Emergence of SARS-CoV-2 through recombination and strong purifying selection. Pangolins may have incubated the novel coronavirus, gene study shows Decimal years are shown on the x axis for the 1.2 years of SARS sampling in c. d, Mean evolutionary rate estimates plotted against sampling time range for the same three datasets (represented by the same colour as the data points in their respective RtT divergence plots), as well as for the comparable NRA3 using the two different priors for the rate in the Bayesian inference (red points). PubMed Central RegionsAC had similar phylogenetic relationships among the southern China bat viruses (Yunnan, Guangxi and Guizhou provinces), the Hong Kong viruses, northern Chinese viruses (Jilin, Shanxi, Hebei and Henan provinces, including Shaanxi), pangolin viruses and the SARS-CoV-2 lineage. Sibling lineages to RaTG13/SARS-CoV-2 include a pangolin sequence sampled in Guangdong Province in March 2019 and a clade of pangolin sequences from Guangxi Province sampled in 2017. with an alignment on which an initial recombination analysis was done. Mol. The proximal origin of SARS-CoV-2 | Nature Medicine Our third approach involved identifying breakpoints and masking minor recombinant regions (with gaps, which are treated as unobserved characters in probabilistic phylogenetic approaches). Of the nine breakpoints defining these ten BFRs, four showed phylogenetic incongruence (PI) signals with bootstrap support >80%, adopting previously published criteria on using a combination of mosaic and PI signals to show evidence of past recombination events19. 206298/Z/17/Z. & Holmes, E. C. A genomic perspective on the origin and emergence of SARS-CoV-2. We thank originating laboratories at South China Agricultural University (Y. Shen, L. Xiao and W. Chen; no. the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Evol. Virological.org http://virological.org/t/ncov-2019-codon-usage-and-reservoir-not-snakes-v2/339 (2020). https://doi.org/10.1093/molbev/msaa163 (2020). Pangolin was developed to implement the dynamic nomenclature of SARS-CoV-2 lineages, known as the Pango nomenclature. 2). Nucleotide positions for phylogenetic inference are 147695, 9621,686 (first tree), 3,6259,150 (second tree, also BFR B), 9,26111,795 (third tree, also BFR C), 12,44319,638 (fourth tree) and 23,63124,633, 24,79525,847, 27,70228,843 and 29,57430,650 (fifth tree). Softw. Developed by the Centre for Genomic Pathogen Surveillance. Collectively our analyses point to bats being the primary reservoir for the SARS-CoV-2 lineage. 725422-ReservoirDOCS). 90, 71847195 (2016). Visual exploration using TempEst39 indicates that there is no evidence for temporal signal in these datasets (Extended Data Fig. Phylogenetic supertree reveals detailed evolution of SARS-CoV-2, Origin and cross-species transmission of bat coronaviruses in China, Emerging SARS-CoV-2 variants follow a historical pattern recorded in outgroups infecting non-human hosts, Inferring the ecological niche of bat viruses closely related to SARS-CoV-2 using phylogeographic analyses of Rhinolophus species, Genomic recombination events may reveal the evolution of coronavirus and the origin of SARS-CoV-2, A Bayesian approach to infer recombination patterns in coronaviruses, Metagenomic identification of a new sarbecovirus from horseshoe bats in Europe, A comparative recombination analysis of human coronaviruses and implications for the SARS-CoV-2 pandemic, Pandemic-scale phylogenomics reveals the SARS-CoV-2 recombination landscape, https://github.com/plemey/SARSCoV2origins, https://doi.org/10.1101/2020.04.20.052019, https://doi.org/10.1101/2020.02.10.942748, https://doi.org/10.1101/2020.05.28.122366, http://virological.org/t/ncov-2019-codon-usage-and-reservoir-not-snakes-v2/339, http://virological.org/t/ncovs-relationship-to-bat-coronaviruses-recombination-signals-no-snakes-no-evidence-the-2019-ncov-lineage-is-recombinant/331. In this study, we report the case of a child with severe combined immu presenting a prolonged severe acute respiratory syndrome coronavirus 2 infection. Nature 503, 535538 (2013). Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. Conservatively, we combined the three BFRs >2kb identified above into non-recombining region1 (NRR1). Figure 1 (top) shows the distribution of all identified breakpoints (using 3SEQs exhaustive triplet search) by the number of candidate recombinant sequences supporting them. 82, 48074811 (2008). The Pango dynamic nomenclature is a popular system for classifying and naming genetically-distinct lineages of SARS-CoV-2, including variants of concern, and is based on the analysis of complete or near-complete virus genomes. Trova, S. et al. 11,12,13,22,28)a signal that suggests recombinationthe divergence patterns in the Sprotein do not show evidence of recombination between the lineage leading to SARS-CoV-2 and known sarbecoviruses. Despite the high frequency of recombination among bat viruses, the block-like nature of the recombination patterns across the genome permits retrieval of a clean subalignment for phylogenetic analysis. J. Virol. 1, vev003 (2015). A second breakpoint-conservative approach was conservative with respect to breakpoint identification, but this means that it is accepting of false-negative outcomes in breakpoint inference, resulting in less certainty that a putative NRR truly contains no breakpoints. We infer time-measured evolutionary histories using a Bayesian phylogenetic approach while incorporating rate priors based on mean MERS-CoV and HCoV-OC43 rates and with standard deviations that allow for more uncertainty than the empirical estimates for both viruses (see Methods). This commit does not belong to any branch on this repository, and may belong to a fork outside of the repository. Rambaut, A., Lam, T. T., Carvalho, L. M. & Pybus, O. G. Exploring the temporal structure of heterochronous sequences using TempEst (formerly Path-O-Gen). Overview of the SARS-CoV-2 genotypes circulating in Latin America Sliding window analysis of changes in the patterns of sequence similarity between human SARS-CoV-2, and pangolin and bat coronaviruses as described further in Fig. Proc. Transparent bands of interquartile range width and with the same colours are superimposed to highlight the overlap between estimates. Sequences were aligned by MAFTT58 v.7.310, with a final alignment length of 30,927, and used in the analyses below. Except for specifying that sequences are linear, all settings were kept to their defaults. The unsampled diversity descended from the SARS-CoV-2/RaTG13 common ancestor forms a clade of bat sarbecoviruses with generalist propertieswith respect to their ability to infect a range of mammalian cellsthat facilitated its jump to humans and may do so again. The estimated divergence times for the pangolin virus most closely related to the SARS-CoV-2/RaTG13 lineage range from 1851 (17301958) to 1877 (17461986), indicating that these pangolin lineages were acquired from bat viruses divergent to those that gave rise to SARS-CoV-2. Trends Microbiol. However, formal testing using marginal likelihood estimation41 does provide some evidence of a temporal signal, albeit with limited log Bayes factor support of 3 (NRR1), 10 (NRR2) and 3 (NRA3); see Supplementary Table 1. A counting renaissance: combining stochastic mapping and empirical Bayes to quickly detect amino acid sites under positive selection. 5 Comparisons of GC content across taxa. Researchers in the UK had just set the scientific world . The assumption of long-term purifying selection would imply that coronaviruses are in endemic equilibrium with their natural host species, horseshoe bats, to which they are presumably well adapted. Results and discussion Genomic surveillance has been a hallmark of the COVID-19 pandemic that, in contrast to other pandemics, achieves tracking of the virus evolution and spread worldwide almost in real-time ( 4 ). P.L. Bayesian phylogenetic and phylodynamic data integration using BEAST 1.10. Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins. covid19_mostefai2021_paper/01_CreateObjects.r at master HussinLab 91, 10581062 (2010). For the current pandemic, the novel pathogen identification component of outbreak response delivered on its promise, with viral identification and rapid genomic analysis providing a genome sequence and confirmation, within weeks, that the December 2019 outbreak first detected in Wuhan, China was caused by a coronavirus3. The lineage B.1 has been the major basal and widespread lineage from the initial SARS-CoV-2 spread and it became the more prevalent lineage in Colombia ( 13 ), while the B.1.111 lineage, first detected in the USA from a sample collected on March 7, 2020 and subsequently in Colombia on March 13, 2020 is currently circulating and mainly represented 68, 10521061 (2019). Thank you for visiting nature.com. Effect of closure of live poultry markets on poultry-to-person transmission of avian influenza A H7N9 virus: an ecological study. 88, 70707082 (2014). Five example sequences with incongruent phylogenetic positions in the two trees are indicated by dashed lines. G066215N, G0D5117N and G0B9317N)) and by the European Unions Horizon 2020 project MOOD (no. MERS-CoV data were subsampled to match sample sizes with SARS-CoV and HCoV-OC43. More evidence Pangolin not intermediary in transmission of SARS-CoV-2 Wang, L. et al. Identifying SARS-CoV-2-related coronaviruses in Malayan pangolins. NTD, N-terminal domain; CTD, C-terminal domain. PANGOLIN lineage database (15, 16) was used to analyze the frequency of lineages among countries. is funded by The National Natural Science Foundation of China Excellent Young Scientists Fund (Hong Kong and Macau; no. Ji, W., Wang, W., Zhao, X., Zai, J. Publishers note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. A., Filip, I., AlQuraishi, M. & Rabadan, R. Recombination and lineage-specific mutations led to the emergence of SARS-CoV-2. For coronaviruses, however, recombination means that small genomic subregions can have independent origins, identifiable if sufficient sampling has been done in the animal reservoirs that support the endemic circulation, co-infection and recombination that appear to be common. We focused on these three non-recombining regions/alignments for divergence time estimation; this avoids inappropriate modelling of evolutionary processes with recombination on strictly bifurcating trees, which can result in different artefacts such as homoplasies that inflate branch lengths and lead to apparently longer evolutionary divergence times. Host ecology determines the dispersal patterns of a plant virus. Cov-Lineages MC_UU_1201412). Anderson, K. G., Rambaut, A., Lipkin, W. I., Holmes, E. C. & Garry, R. F. The proximal origin of SARS-CoV-2. P.L. The virus then. PubMed Boni, M.F., Lemey, P., Jiang, X. et al. b, Similarity plot between SARS-CoV-2 and several selected sequences including RaTG13 (black), SARS-CoV (pink) and two pangolin sequences (orange). Biol. =0.00025. Liu, P. et al. B.W.P. Lu, R. et al. In our second stage, we wanted to construct non-recombinant regions where our approach to breakpoint identification was as conservative as possible. Proc. The authors declare no competing interests. Combining regions A, B and C and removing the five named sequences gives us putative NRR1, as an alignment of 63sequences. By 2009, however, rapid genomic analysis had become a routine component of outbreak response. Forni, D., Cagliani, R., Clerici, M. & Sironi, M. Molecular evolution of human coronavirus genomes. . Curr. Posterior means (horizontal bars) of patristic distances between SARS-CoV-2 and its closest bat and pangolin sequences, for the spike proteins variable loop region and CTD region excluding the variable loop.