pangolin lineage covid

1, vev016 (2015). Katoh, K., Asimenos, G. & Toh, H. in Bioinformatics for DNA Sequence Analysis (ed. Wang, H., Pipes, L. & Nielsen, R. Synonymous mutations and the molecular evolution of SARS-Cov-2 origins. 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. Is the COVID-19 Outbreak the 'Revenge of the Pangolin'? | PETA The origins we present in Fig. Wu, Y. et al. 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. However, for several reasons, nucleotide sequences may be generated that cover only the spike gene of SARS-CoV-2. 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. All authors contributed to analyses and interpretations. NTD, N-terminal domain; CTD, C-terminal domain. 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). We extracted a similar number (n=35) of genomes from a MERS-CoV dataset analysed by Dudas et al.59 using the phylogenetic diversity analyser tool60 (v.0.5). J. Virol. Smuggled pangolins were carrying viruses closely related to the one sweeping the world, say scientists. T.T.-Y.L. 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. J. Infect. One study suggests that over a century ago, one lineage of coronavirus circulating in bats gave rise to SARS-CoV-2, RaTG13 and a Pangolin coronavirus known as Pangolin-2019, Live Science . 91, 10581062 (2010). Lam, H. M., Ratmann, O. Publishers note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Visual exploration using TempEst39 indicates that there is no evidence for temporal signal in these datasets (Extended Data Fig. 5 Comparisons of GC content across taxa. Wang, L. et al. According to GISAID . Virological.org http://virological.org/t/ncov-2019-codon-usage-and-reservoir-not-snakes-v2/339 (2020). Here, we analyse the evolutionary history of SARS-CoV-2 using available genomic data on sarbecoviruses. These datasets were subjected to the same recombination masking approach as NRA3 and were characterized by a strong temporal signal (Fig. 3). Yu, H. et al. We used TreeAnnotator to summarize posterior tree distributions and annotated the estimated values to a maximum clade credibility tree, which was visualized using FigTree. It performs: K-mer based detection Map/align, variant calling Consensus sequence generation Lineage/clade analysis using Pangolin and NextClade Access the DRAGEN COVID Lineage App on BaseSpace Sequence Hub Trends Microbiol. The research leading to these results received funding (to A.R. DRAGEN COVID Lineage App This app aligns reads to a SARS-CoV-2 reference genome and reports coverage of targeted regions. But some theories suggest that pangolins may be the source of the novel coronavirus. Yres, D. L. et al. Many Git commands accept both tag and branch names, so creating this branch may cause unexpected behavior. 1a-c ), has the third-highest number of confirmed COVID-19 cases in the state of So. 5 (NRR1) are conservative in the sense that NRR1 is more likely to be non-recombinant than NRR2 or NRA3. PubMed Bruen, T. C., Philippe, H. & Bryant, D. A simple and robust statistical test for detecting the presence of recombination. Even before the COVID-19 pandemic, pangolins have been making headlines. A phylogenetic treeusing RAxML v8.2.8 (ref. PDF single centre retrospective study 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. 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. [12] This study provides an integration of existing classifications and describes evolutionary trends of the SARS-CoV . Because these subclades had different phylogenetic relationships in regionD (Supplementary Fig. 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. 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 . Duchene, S., Holmes, E. C. & Ho, S. Y. W. Analyses of evolutionary dynamics in viruses are hindered by a time-dependent bias in rate estimates. Emerg. 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. 1. Evol. Stegeman, A. et al. Boni, M. F., Posada, D. & Feldman, M. W. An exact nonparametric method for inferring mosaic structure in sequence triplets. Mol. Pangolin relies on a novel algorithm called pangoLEARN. 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. Lam, T. T. et al. Hon, C. et al. Instead, similarity in codon usage metrics between the SARS-CoV-2 and eukaryotes analyzed was correlated with coding sequence GC content of the eukaryote, with more similar codon usage being identified in eukaryotes with low GC content similar to that of the coronavirus (b). and JavaScript. Abstract. 3) clusters with viruses from provinces in the centre, east and northeast of China. 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. PubMed 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). Lancet 395, 949950 (2020). T.L. Because 3SEQ is the most statistically powerful of the mosaic methods61, we used it to identify the best-supported breakpoint history for each potential child (recombinant) sequence in the dataset. 95% credible interval bars are shown for all internal node ages. 21, 15081514 (2015). 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. Don't blame pangolins, coronavirus family tree tracing could prove key Pangolin was developed to implement the dynamic nomenclature of SARS-CoV-2 lineages, known as the Pango nomenclature. 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. Which animal did the novel coronavirus come from? | Live Science 30, 21962203 (2020). The proximal origin of SARS-CoV-2 | Nature Medicine We compare both MERS-CoV- and HCoV-OC43-centred prior distributions (Extended Data Fig. Virus Evol. A new SARS-CoV-2 variant (B.1.1.523) capable of escaping immune protections Are you sure you want to create this branch? 3 Priors and posteriors for evolutionary rate of SARS-CoV-2. These are in general agreement with estimates using NRR2 and NRA3, which result in divergence times of 1982 (19482009) and 1948 (18791999), respectively, for SARS-CoV-2, and estimates of 1952 (19061989) and 1970 (19321996), respectively, for the divergence time of SARS-CoV from its closest known bat relative. Temporal signal was tested using a recently developed marginal likelihood estimation procedure41 (Supplementary Table 1). Wong, A. C. P., Li, X., Lau, S. K. P. & Woo, P. C. Y. Python 379 102 pangoLEARN Public Store of the trained model for pangolin to access. Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus. 25, 3548 (2017). 4 we compare these divergence time estimates to those obtained using the MERS-CoV-centred rate priors for NRR1, NRR2 and NRA3. Influenza viruses reassort17 but they do not undergo homologous recombination within RNA segments18,19, meaning that origins questions for influenza outbreaks can always be reduced to origins questions for each of influenzas eight RNA segments. Membrebe, J. V., Suchard, M. A., Rambaut, A., Baele, G. & Lemey, P. Bayesian inference of evolutionary histories under time-dependent substitution rates. Concurrent evidence also proposed pangolins as a potential intermediate species for SARS-CoV-2 emergence and suggested them as a potential reservoir species11,12,13. 6, e14 (2017). Mol. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. J. Virol. In regionA, we removed subregion A1 (ntpositions 3,8724,716 within regionA) and subregion A4 (nt1,6422,113) because both showed PI signals with other subregions of regionA. performed recombination analysis for non-recombining alignment3, calibration of rate of evolution and phylogenetic reconstruction and dating. Download a free copy. Using these breakpoints, the longest putative non-recombining segment (nt1,88521,753) is 9.9kb long, and we call this region NRR2. D.L.R. 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. The pangolin coronaviruses show lower similarity to SARS-CoV-2 than bat coronavirus RaTG13 across the whole genome, but higher similarity in the spike receptor binding domain, although the similarity at either scale remains too low to implicate . Bryant, D. & Moulton, V. Neighbor-Net: an agglomerative method for the construction of phylogenetic networks. Google Scholar. On first examination this would suggest that that SARS-CoV-2 is a recombinant of an ancestor of Pangolin-2019 and RaTG13, as proposed by others11,22. 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. 36)gives a putative recombination-free alignment that we call non-recombinant alignment3 (NRA3) (see Methods). 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. This underscores the need for a global network of real-time human disease surveillance systems, such as that which identified the unusual cluster of pneumonia in Wuhan in December 2019, with the capacity to rapidly deploy genomic tools and functional studies for pathogen identification and characterization. Published. 26 March 2020. Bioinformatics 22, 26882690 (2006). J. Virol. Coronavirus: Pangolins found to carry related strains - BBC News 110. Google Scholar. Evidence of the recombinant origin of a bat severe acute respiratory syndrome (SARS)-like coronavirus and its implications on the direct ancestor of SARS coronavirus. By mid-January 2020, the virus was spreading widely within Hubei province and by early March SARS-CoV-2 was declared a pandemic8. Epidemiology, genetic recombination, and pathogenesis of coronaviruses. Pangolin-CoV is 91.02% and 90.55% identical to SARS-CoV-2 and BatCoV RaTG13, respectively, at the whole-genome level. 2 Lack of root-to-tip temporal signal in SARS-CoV-2. The web application was developed by the Centre for Genomic Pathogen Surveillance. PI signals were identified (with bootstrap support >80%) for seven of these eight breakpoints: positions 1,684, 3,046, 9,237, 11,885, 21,753, 22,773 and 24,628. 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. ac, Root-to-tip (RtT) divergence as a function of sampling time for the three coronavirus evolutionary histories unfolding over different timescales (HCoV-OC43 (n=37; a) MERS (n=35; b) and SARS (n=69; c)). There is a 90% DNA match between SARS CoV 2 and a coronavirus in pangolins. Liu, P. et al. Patino-Galindo, J. MC_UU_1201412). 88, 70707082 (2014). RegionB is 5,525nt long. Sequences are colour-coded by province according to the map. As a proxy, it would be possible to model the long-term purifying selection dynamics as a major source of time-dependent rates43,44,52, but this is beyond the scope of the current study. Anderson, K. G. nCoV-2019 codon usage and reservoir (not snakes v2). Coronavirus: Pangolins may have spread the disease to humans 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. Coronavirus: Pangolins found to carry related strains. Zhang, Y.-Z. Evol. N. China corresponds to Jilin, Shanxi, Hebei and Henan provinces, and the N. China clade also includes one sequence sampled in Hubei Province in 2004. Evol. Transparent bands of interquartile range width and with the same colours are superimposed to highlight the overlap between estimates. 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. Nat. 16, e1008421 (2020). Zhou, H. et al. Xiao, K. et al. A distinct name is needed for the new coronavirus. 4. In our second stage, we wanted to construct non-recombinant regions where our approach to breakpoint identification was as conservative as possible. 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). Article In such cases, even moderate rate variation among long, deep phylogenetic branches will substantially impact expected root-to-tip divergences over a sampling time range that represents only a small fraction of the evolutionary history40. J. Virol. All sequence data analysed in this manuscript are available at https://github.com/plemey/SARSCoV2origins. PubMed Central Proc. S. China corresponds to Guangxi, Yunnan, Guizhou and Guangdong provinces. We thank T. Bedford for providing M.F.B. Syst. Pangolin was developed to implement the dynamic nomenclature of SARS-CoV-2 lineages, known as the Pango nomenclature. 6, eabb9153 (2020). In the presence of time-dependent rate variation, a widely observed phenomenon for viruses43,44,52, slower prior rates appear more appropriate for sarbecoviruses that currently encompass a sampling time range of about 18years. 90, 71847195 (2016). Identifying the origins of an emerging pathogen can be critical during the early stages of an outbreak, because it may allow for containment measures to be precisely targeted at a stage when the number of daily new infections is still low. Anderson, K. G., Rambaut, A., Lipkin, W. I., Holmes, E. C. & Garry, R. F. The proximal origin of SARS-CoV-2. Genet. 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. With horseshoe bats currently the most plausible origin of SARS-CoV-2, it is important to consider that sarbecoviruses circulate in a variety of horseshoe bat species with widely overlapping species ranges57. Pangolins may have incubated the novel coronavirus, gene study shows Google Scholar. Press, H.) 3964 (Springer, 2009). Of the countries that have contributed SARS-CoV-2 data, 30% had genomes of this lineage. Nature 579, 265269 (2020). Centre for Genomic Pathogen Surveillance. The Bat, the Pangolin and the City: A Tale of COVID-19 Yuan, J. et al. Sequence similarity. 36, 7597 (2002). It allows a user to assign a SARS-CoV-2 genome sequence the most likely lineage (Pango lineage) to SARS-CoV-2 query sequences. 4). Biazzo et al. Boni, M. F., de Jong, M. D., van Doorn, H. R. & Holmes, E. C. Guidelines for identifying homologous recombination events in influenza A virus. A hypothesis of snakes as intermediate hosts of SARS-CoV-2 was posited during the early epidemic phase54, but we found no evidence of this55,56; see Extended Data Fig. Evol. Graham, R. L. & Baric, R. S. Recombination, reservoirs, and the modular spike: mechanisms of coronavirus cross-species transmission. J. Med. Thank you for visiting nature.com. Open reading frames are shown above the breakpoint plot, with the variable-loop region indicated in the Sprotein. The idea is that pangolins carrying the virus, SARS-CoV-2, came into contact with humans. Zhou, P. et al. Evol. 82, 48074811 (2008). 1c). It compares the new genome against the large, diverse population of sequenced strains using a Cell 181, 223227 (2020). CoV-lineages GitHub 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. Relevant bootstrap values are shown on branches, and grey-shaded regions show sequences exhibiting phylogenetic incongruence along the genome. A., Lytras, S., Singer, J. All custom code used in the manuscript is available at https://github.com/plemey/SARSCoV2origins.

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