These shy, quirky but cute mammals are one of the most heavily trafficked yet least understood animals in the world. This new approach classifies the newly sequenced genome against all the diverse lineages present instead of a representative select sequences. We showed that severe acute respiratory syndrome coronavirus 2 is probably a novel recombinant virus. Posterior distributions were approximated through Markov chain Monte Carlo sampling, which were run sufficiently long to ensure effective sampling sizes >100. Since experts have suggested that pangolins may be the reservoir species for COVID-19, the scaly anteater has been catapulted into headlines, news reports, and conversationsand some are calling COVID-19 "the revenge of the . J. Med. Avian influenza a virus (H7N7) epidemic in The Netherlands in 2003: course of the epidemic and effectiveness of control measures. Divergence dates between SARS-CoV-2 and the bat sarbecovirus reservoir were estimated as 1948 (95% highest posterior density (HPD): 18791999), 1969 (95% HPD: 19302000) and 1982 (95% HPD: 19482009), indicating that the lineage giving rise to SARS-CoV-2 has been circulating unnoticed in bats for decades. Individual sequences such as RpShaanxi2011, Guangxi GX2013 and two sequences from Zhejiang Province (CoVZXC21/CoVZC45), as previously shown22,25, have strong phylogenetic recombination signals because they fall on different evolutionary lineages (with bootstrap support >80%) depending on what region of the genome is being examined. & Holmes, E. C. A genomic perspective on the origin and emergence of SARS-CoV-2. with an alignment on which an initial recombination analysis was done. Curr. MC_UU_1201412). 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. Sequence similarity. The shaded region corresponds to the Sprotein. Green boxplots show the TMRCA estimate for the RaTG13/SARS-CoV-2 lineage and its most closely related pangolin lineage (Guangdong 2019), with the light and dark coloured version based on the HCoV-OC43 and MERS-CoV centred priors, respectively. eLife 7, e31257 (2018). 21, 255265 (2004). As informative rate priors for the analysis of the sarbecovirus datasets, we used two different normal prior distributions: one with a mean of 0.00078 and s.d. Across a large region of the virus genome, corresponding approximately to ORF1b, it did not cluster with any of the known bat coronaviruses indicating that recombination probably played a role in the evolutionary history of these viruses5,7. To examine temporal signal in the sequenced data, we plotted root-to-tip divergence against sampling time using TempEst39 v.1.5.3 based on a maximum likelihood tree. In our analyses of the sarbecovirus datasets, we incorporated the uncertainty of the sampling dates when exact dates were not available. BEAST inferences made use of the BEAGLE v.3 library68 for efficient likelihood computations. 91, 10581062 (2010). It compares the new genome against the large, diverse population of sequenced strains using a The ongoing pandemic spread of a new human coronavirus, SARS-CoV-2, which is associated with severe pneumonia/disease (COVID-19), has resulted in the generation of tens of thousands of virus . DRAGEN COVID Lineage App This app aligns reads to a SARS-CoV-2 reference genome and reports coverage of targeted regions. Martin, D. P., Murrell, B., Golden, M., Khoosal, A. Among the 68sequences in the aligned sarbecovirus sequence set, 67 show evidence of mosaicism (all DunnSidak-corrected P<4104 and 3SEQ14), indicating involvement in homologous recombination either directly with identifiable parentals or in their deeper shared evolutionary historythat is, due to shared ancestral recombination events. Nat. A distinct name is needed for the new coronavirus. Using both prior distributions, this results in six highly similar posterior rate estimates for NRR1, NRR2 and NRA3, centred around 0.00055 substitutions per siteyr1. a, Breakpoints identified by 3SEQ illustrated by percentage of sequences (out of 68) that support a particular breakpoint position. Are you sure you want to create this branch? The estimated divergence times for the pangolin virus most closely related to the SARS-CoV-2/RaTG13 lineage range from 1851 (1730-1958) to 1877 (1746-1986), indicating that these pangolin . Internet Explorer). Coronavirus Disease 2019 (COVID-19) Situation Report 51 (World Health Organization, 2020). Alternatively, combining 3SEQ-inferred breakpoints, GARD-inferred breakpoints and the necessity of PI signals for inferring recombination, we can use the 9.9-kb region spanning nucleotides 11,88521,753 (NRR2) as a putative non-recombining region; this approach is breakpoint-conservative because it is conservative in identifying breakpoints but not conservative in identifying non-recombining regions. 90, 71847195 (2016). Emerg. Zhou, P. et al. 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. A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. PureBasic 53 13 constellations Public Python 42 17 And this genotype pattern led to creating a new Pangolin lineage named B.1.640.2, a phylogenetic sister group to the old B.1.640 lineage renamed B.1.640.1. Its genome is closest to that of severe acute respiratory syndrome-related coronaviruses from horseshoe bats, and its receptor-binding domain is closest to that of pangolin viruses. 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 5 Comparisons of GC content across taxa. Lin, X. et al. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. The consistency of the posterior rates for the different prior means also implies that the data do contribute to the evolutionary rate estimate, despite the fact that a temporal signal was visually not apparent (Extended Data Fig. If the latter still identified non-negligible recombination signal, we removed additional genomes that were identified as major contributors to the remaining signal. Lancet 395, 949950 (2020). Virus Evol. R. Soc. The new paper finds that the genetic sequences of several strains of coronavirus found in pangolins were between 88.5 percent and 92.4 percent similar to those of the novel coronavirus. Virological.org http://virological.org/t/ncov-2019-codon-usage-and-reservoir-not-snakes-v2/339 (2020). 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). Nature 583, 286289 (2020). According to GISAID . 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. 1, vev003 (2015). Effect of closure of live poultry markets on poultry-to-person transmission of avian influenza A H7N9 virus: an ecological study. Genetics 172, 26652681 (2006). performed recombination analysis for non-recombining regions1 and 2, breakpoint analysis and phylogenetic inference on recombinant segments. 94, e0012720 (2020). Nature 558, 180182 (2018). CAS We call this approach breakpoint-conservative, but note that this has the opposite effect to the construction of NRR1 in that this approach is the most likely to allow breakpoints to remain inside putative non-recombining regions. Viruses 11, 979 (2019). Holmes, E. C., Rambaut, A. Anderson, K. G. nCoV-2019 codon usage and reservoir (not snakes v2). The time-calibrated phylogeny represents a maximum clade credibility tree inferred for NRR1. 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. Sorting these breakpoint-free regions (BFRs) by length results in two segments >5kb: an ORF1a subregion spanning nucleotides (nt) 3,6259,150 and the first half of ORF1b spanning nt13,29119,628 (sequence numbering given in Source Data, https://github.com/plemey/SARSCoV2origins). Zhang, Y.-Z. The coverage threshold and consensus sequence generation threshold were set to 20 and 90 respectively. the development of viral diversity. performed Srecombination analysis. The most parsimonious explanation for these shared ACE2-specific residues is that they were present in the common ancestors of SARS-CoV-2, RaTG13 and Pangolin Guangdong 2019, and were lost through recombination in the lineage leading to RaTG13. Wong, A. C. P., Li, X., Lau, S. K. P. & Woo, P. C. Y. Concatenated region ABC is NRR1. 3) to examine the sensitivity of date estimates to this prior specification. At present, we analyzed the diversity of SARS-CoV-2 viral genomes in India to know the evolutionary patterns of viruses in the country through their pangolin lineage and GISAID-Clade. performed recombination and phylogenetic analysis and annotated virus names with geographical and sampling dates. 26 March 2020. PubMed Central All authors contributed to analyses and interpretations. After removal of A1 and A4, we named the new region A. Indeed, the rates reported by these studies are in line with the short-term SARS rates that we estimate (Fig. Pangolin relies on a novel algorithm called pangoLEARN. Lam, T. T. et al. Get the most important science stories of the day, free in your inbox. Natl Acad. Here, we analyse the evolutionary history of SARS-CoV-2 using available genomic data on sarbecoviruses. Researchers in the UK had just set the scientific world . In December 2019, a cluster of pneumonia cases epidemiologically linked to an open-air live animal market in the city of Wuhan (Hubei Province), China1,2 led local health officials to issue an epidemiological alert to the Chinese Center for Disease Control and Prevention and the World Health Organizations (WHO) China Country Office. 5, 536544 (2020). 04:20. Hu, B. et al. 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. Many Git commands accept both tag and branch names, so creating this branch may cause unexpected behavior. You signed in with another tab or window. b, Similarity plot between SARS-CoV-2 and several selected sequences including RaTG13 (black), SARS-CoV (pink) and two pangolin sequences (orange). Li, X. et al. This provides compelling support for the SARS-CoV-2 lineage being the consequence of a direct or nearly-direct zoonotic jump from bats, because the key ACE2-binding residues were present in viruses circulating in bats. Pink, green and orange bars show BFRs, with regionA (nt 13,29119,628) showing two trimmed segments yielding regionA (nt13,29114,932, 15,40517,162, 18,00919,628). Stamatakis, A. RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models. Trova, S. et al. Unfortunately, a response that would achieve containment was not possible. EPI_ISL_410721) and Beijing Institute of Microbiology and Epidemiology (W.-C. Cao, T.T.-Y.L., N. Jia, Y.-W. Zhang, J.-F. Jiang and B.-G. Jiang, nos. 1c). When the first genome sequence of SARS-CoV-2, Wuhan-Hu-1, was released on 10January 2020 (GMT) on Virological.org by a consortium led by Zhang6, it enabled immediate analyses of its ancestry. 1, vev016 (2015). & Andersen, K. G. The evolution of Ebola virus: insights from the 20132016 epidemic. However, on closer inspection, the relative divergences in the phylogenetic tree (Fig. Publishers note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. J. Virol. The difficulty in inferring reliable evolutionary histories for coronaviruses is that their high recombination rate48,49 violates the assumption of standard phylogenetic approaches because different parts of the genome have different histories. (Yes, Pango is a tongue-in-cheek reference to pangolins, which were briefly suspected to have had a role in the coronavirus's originseveral of the team's computational tools are named after. matics program called Pangolin was developed. 4), but also by markedly different evolutionary rates. Lemey, P., Minin, V. N., Bielejec, F., Pond, S. L. K. & Suchard, M. A. and X.J. Five example sequences with incongruent phylogenetic positions in the two trees are indicated by dashed lines. Because coronaviruses are known to be highly recombinant, we used three different approaches to identify non-recombinant regions for use in our Bayesian time-calibrated phylogenetic inference. SARS-CoV-2 genetic lineages in the United States are routinely monitored through epidemiological investigations, virus genetic sequence-based surveillance, and laboratory studies. Evol. We thank originating laboratories at South China Agricultural University (Y. Shen, L. Xiao and W. Chen; no. The fact that they are geographically relatively distant is in agreement with their somewhat distant TMRCA, because the spatial structure suggests that migration between their locations may be uncommon. 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). Emergence of SARS-CoV-2 through recombination and strong purifying selection. Virology 507, 110 (2017). Slider with three articles shown per slide. The idea is that pangolins carrying the virus, SARS-CoV-2, came into contact with humans. Schierup, M. H. & Hein, J. Recombination and the molecular clock. Region A has been shortened to A (5,017nt) based on potential recombination signals within the region. Methods Ecol. 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. Biol. Complete genome sequence data were downloaded from GenBank and ViPR; accession numbers of all 68sequences are available in Supplementary Table 4. This dataset comprises an updated version of that used in Hon et al.15 and includes a cluster of genomes sampled in late 2003 and early 2004, but the evolutionary rate estimate without this cluster (0.00175 substitutions per siteyr1 (0.00117,0.00229)) is consistent with the complete dataset (0.00169 substitutions per siteyr1, (0.00131,0.00205)). Using these breakpoints, the longest putative non-recombining segment (nt1,88521,753) is 9.9kb long, and we call this region NRR2. Menachery, V. D. et al. Mol. 382, 11991207 (2020). 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. 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. pango-designation Public Repository for suggesting new lineages that should be added to the current scheme Python 968 73 pangolin Public Software package for assigning SARS-CoV-2 genome sequences to global lineages. Sequences are colour-coded by province according to the map. 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). 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. PLoS ONE 5, e10434 (2010). "This is an extremely interesting . Published. The rate of genome generation is unprecedented, yet there is currently no coherent nor accepted scheme for naming the expanding . (2020) with additional (and higher quality) snake coding sequence data and several miscellaneous eukaryotes with low genomic GC content failed to find any meaningful clustering of the SARS-CoV-2 with snake genomes (a). Sign up for the Nature Briefing newsletter what matters in science, free to your inbox daily. 36) (RDP, GENECONV, MaxChi, Bootscan, SisScan and 3SEQ) and considered recombination signals detected by more than two methods for breakpoint identification. Cell 181, 223227 (2020). Sci. N. Engl. Divergence time estimates based on the three regions/alignments where the effects of recombination have been removed. Download a free copy. The presence of SARS-CoV-2-related viruses in Malayan pangolins, in silico analysis of the ACE2 receptor polymorphism and sequence similarities between the Receptor Binding Domain (RBD) of the spike proteins of pangolin and human Sarbecoviruses led to the proposal of pangolin as intermediary. Zhou et al.2 concluded from the genetic proximity of SARS-CoV-2 to RaTG13 that a bat origin for the current COVID-19 outbreak is probable. 3). Add entries for pangolin-data/-assignment 1.18.1.1 (, Really add a document on testing strategy. You are using a browser version with limited support for CSS. 35, 247251 (2018). Developed by the Centre for Genomic Pathogen Surveillance. Its origin and direct ancestral viruses have not been . J. Virol. & Bedford, T. MERS-CoV spillover at the camelhuman interface. 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. We named the length-sorted BFRs as: BFRA (ntpositions 13,29119,628, length=6,338nt), BFRB (ntpositions 3,6259,150, length=5,526nt), BFRC (ntpositions 9,26111,795, length=2,535nt), BFRD (ntpositions 27,70228,843, length=1,142nt) and six further regions (EJ). J. Virol. MERS-CoV data were subsampled to match sample sizes with SARS-CoV and HCoV-OC43. 1a-c ), has the third-highest number of confirmed COVID-19 cases in the state of So. 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. and P.L.) 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. Relevant bootstrap values are shown on branches, and grey-shaded regions show sequences exhibiting phylogenetic incongruence along the genome. Coronavirus: Pangolins found to carry related strains. All sequence data analysed in this manuscript are available at https://github.com/plemey/SARSCoV2origins. Ji, W., Wang, W., Zhao, X., Zai, J. The S1 protein of Pangolin-CoV is much more closely related to SARS-CoV-2 than to RaTG13. Intraspecies diversity of SARS-like coronaviruses in Rhinolophus sinicus and its implications for the origin of SARS coronaviruses in humans. 82, 18191826 (2008). 1 Phylogenetic relationships in the C-terminal domain (CTD). Syst. PLoS Pathog. 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). volume5,pages 14081417 (2020)Cite this article. Note that breakpoints can be shared between sequences if they are descendants of the same recombination events. Maciej F. Boni, Philippe Lemey, Andrew Rambaut or David L. Robertson. 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). Transparent bands of interquartile range width and with the same colours are superimposed to highlight the overlap between estimates. Epidemiology, genetic recombination, and pathogenesis of coronaviruses. A.R. Gorbalenya, A. E. et al. BEAGLE 3: improved performance, scaling, and usability for a high-performance computing library for statistical phylogenetics. This leaves the insertion of polybasic. 2). The presence in pangolins of an RBD very similar to that of SARS-CoV-2 means that we can infer this was also probably in the virus that jumped to humans. Biol. Python 379 102 pangoLEARN Public Store of the trained model for pangolin to access. P.L. We find that the sarbecovirusesthe viral subgenus containing SARS-CoV and SARS-CoV-2undergo frequent recombination and exhibit spatially structured genetic diversity on a regional scale in China. A single 3SEQ run on the genome alignment resulted in 67 out of 68sequences supporting some recombination in the past, with multiple candidate breakpoint ranges listed for each putative recombinant. Holmes, E. C. The Evolution and Emergence of RNA Viruses (Oxford Univ. Of the countries that have contributed SARS-CoV-2 data, 30% had genomes of this lineage. Software package for assigning SARS-CoV-2 genome sequences to global lineages. Lond. 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. Unlike other viruses that have emerged in the past two decades, coronaviruses are highly recombinogenic14,15,16. 36, 7597 (2002). Li, Q. et al. 1. from the European Research Council under the European Unions Horizon 2020 research and innovation programme (grant agreement no. Bioinformatics 30, 13121313 (2014). Collectively our analyses point to bats being the primary reservoir for the SARS-CoV-2 lineage. Google Scholar. These authors contributed equally: Maciej F. Boni, Philippe Lemey. Aiewsakun, P. & Katzourakis, A. Time-dependent rate phenomenon in viruses. Biol. Mol. 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. 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. These residues are also in the Pangolin Guangdong 2019 sequence. Using the most conservative approach (NRR1), the divergence time estimate for SARS-CoV-2 and RaTG13 is 1969 (95% HPD: 19302000), while that between SARS-CoV and its most closely related bat sequence is 1962 (95% HPD: 19321988); see Fig. In addition, sequences NC_014470 (Bulgaria 2008), CoVZXC21, CoVZC45 and DQ412042 (Hubei-Yichang) needed to be removed to maintain a clean non-recombinant signal in A. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for the current coronavirus disease (COVID-19) pandemic that has affected more than 35 million people and caused . Wang, H., Pipes, L. & Nielsen, R. Synonymous mutations and the molecular evolution of SARS-Cov-2 origins. & Muhire, B. RDP4: Detection and analysis of recombination patterns in virus genomes. Humans' selfish, speciesist treatment of these animals could be the very reason why the novel coronavirus exists. CAS 3). Global epidemiology of bat coronaviruses. Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage responsible for the COVID-19 pandemic. PubMed Trends Microbiol. 13, e1006698 (2017). 32, 268274 (2014). Graham, R. L. & Baric, R. S. Recombination, reservoirs, and the modular spike: mechanisms of coronavirus cross-species transmission. 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. Chernomor, O. et al. & Boni, M. F. Improved algorithmic complexity for the 3SEQ recombination detection algorithm. 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. To gauge the length of time this lineage has circulated in bats, we estimate the time to the most recent common ancestor (TMRCA) of SARS-CoV-2 and RaTG13. 36)gives a putative recombination-free alignment that we call non-recombinant alignment3 (NRA3) (see Methods). Time-measured phylogenetic reconstruction was performed using a Bayesian approach implemented in BEAST42 v.1.10.4. Wu, Y. et al. Extensive diversity of coronaviruses in bats from China. We compiled a set of 69SARS-CoV genomes including 58 sampled from humans and 11 sampled from civets and raccoon dogs. Genetic lineages of SARS-CoV-2 have been emerging and circulating around the world since the beginning of the COVID-19 pandemic. Posterior rate distributions for MERS-CoV (far left) and HCoV-OC43 (far right) using BEAST on n=27 sequences spread over 4 years (MERS-CoV) and n=27 sequences spread over 49 years (HCoV-OC43). We thank all authors who have kindly deposited and shared genome data on GISAID. 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. Bayesian phylogenetic and phylodynamic data integration using BEAST 1.10. Even before the COVID-19 pandemic, pangolins have been making headlines. & Andersen, K. G. Pandemics: spend on surveillance, not prediction. Lancet 395, 565574 (2020). Two other bat viruses (CoVZXC21 and CoVZC45) from Zhejiang Province fall on this lineage as recombinants of the RaTG13/SARS-CoV-2 lineage and the clade of Hong Kong bat viruses sampled between 2005 and 2007 (Fig. 36, 17931803 (2019). G066215N, G0D5117N and G0B9317N)) and by the European Unions Horizon 2020 project MOOD (no. 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. and JavaScript. 206298/Z/17/Z. Microbiol. Duchene, S. et al. Green boxplots show the TMRCA estimate for the RaTG13/SARS-CoV-2 lineage and its most closely related pangolin lineage (Guangdong 2019). Figure 1 (top) shows the distribution of all identified breakpoints (using 3SEQs exhaustive triplet search) by the number of candidate recombinant sequences supporting them. Preprint at https://doi.org/10.1101/2020.04.20.052019 (2020). Gray inset shows majority rule consensus trees with mean posterior branch lengths for the two regions, with posterior probabilities on the key nodes showing the relationships among SARS-CoV-2, RaTG13, and Pangolin 2019. Further information on research design is available in the Nature Research Reporting Summary linked to this article. 3). 30, 21962203 (2020). Wu, F. et al. When the genomic data included both coding and non-coding regions we used a single GTR+ substitution model; for concatenated coding genes we partitioned the alignment by codon position and specified an independent GTR+ model for each partition with a separate gamma model to accommodate inter-site rate variation. This is evidence for numerous recombination events occurring in the evolutionary history of the sarbecoviruses22,33; specifying all past events in their correct temporal order34 is challenging and not shown here. Virological.org http://virological.org/t/ncovs-relationship-to-bat-coronaviruses-recombination-signals-no-snakes-no-evidence-the-2019-ncov-lineage-is-recombinant/331 (2020).
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