pangolin lineage covid

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. Nature 558, 180182 (2018). Green boxplots show the TMRCA estimate for the RaTG13/SARS-CoV-2 lineage and its most closely related pangolin lineage (Guangdong 2019). obtained the genome sequences of 10 SARS-CoV-2 virus strains through nanopore sequencing of nasopharyngeal swabs in Malta and analyzed the assembled genome with pangolin software, and the results showed that these virus strains were assigned to B.1 lineage, indicating that SARS-CoV-2 was widely spread in Europe (Biazzo et al., 2021). 3). 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)). Evol. B 281, 20140732 (2014). A.R. This commit does not belong to any branch on this repository, and may belong to a fork outside of the repository. These authors contributed equally: Maciej F. Boni, Philippe Lemey. Forni, D., Cagliani, R., Clerici, M. & Sironi, M. Molecular evolution of human coronavirus genomes. 4), but also by markedly different evolutionary rates. 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. 5. Because these subclades had different phylogenetic relationships in regionD (Supplementary Fig. Host ecology determines the dispersal patterns of a plant virus. Extensive diversity of coronaviruses in bats from China. It is available as a command line tool and a web application. 13, e1006698 (2017). Boni, M.F., Lemey, P., Jiang, X. et al. In the absence of a strong temporal signal, we sought to identify a suitable prior rate distribution to calibrate the time-measured trees by examining several coronaviruses sampled over time, including HCoV-OC43, MERS-CoV, and SARS-CoV virus genomes. Thank you for visiting nature.com. A tag already exists with the provided branch name. Without better sampling, however, it is impossible to estimate whether or how many of these additional lineages exist. The genetic distances between SARS-CoV-2 and RaTG13 (bottom) demonstrate that their relationship is consistent across all regions except for the variable loop. It is available as a command line tool and a web application. Mol. The fact that these estimates lie between the rates for MERS-CoV and HCoV-OC43 is consistent with the intermediate sampling time range of about 18years (Fig. This is not surprising for diverse viral populations with relatively deep evolutionary histories. Virus Evol. Split diversity in constrained conservation prioritization using integer linear programming. Stegeman, A. et al. These means are based on the mean rates estimated for MERS-CoV and HCoV-OC43, respectively, while the standard deviations are set ten times higher than empirical values to allow greater prior uncertainty and avoid strong bias (Extended Data Fig. and P.L.) In Extended Data Fig. 90, 71847195 (2016). Evolutionary rate estimation can be profoundly affected by the presence of recombination50. You signed in with another tab or window. Schierup, M. H. & Hein, J. Recombination and the molecular clock. Ji, W., Wang, W., Zhao, X., Zai, J. PLoS Pathog. BEAST inferences made use of the BEAGLE v.3 library68 for efficient likelihood computations. Yuan, J. 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. 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. Google Scholar. Membrebe, J. V., Suchard, M. A., Rambaut, A., Baele, G. & Lemey, P. Bayesian inference of evolutionary histories under time-dependent substitution rates. Anderson, K. G. nCoV-2019 codon usage and reservoir (not snakes v2). Sign up for the Nature Briefing newsletter what matters in science, free to your inbox daily. We thank T. Bedford for providing M.F.B. A third approach attempted to minimize the number of regions removed while also minimizing signals of mosaicism and homoplasy. Suchard, M. A. et al. However, inconsistency in the nomenclature limits uniformity in its epidemiological understanding. 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. 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. As illustrated by the dashed arrows, these two posteriors motivate our specification of prior distributions with standard deviations inflated 10-fold (light color). We demonstrate that the sarbecoviruses circulating in horseshoe bats have complex recombination histories as reported by others15,20,21,22,23,24,25,26. . 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. 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. Aside from RaTG13, Pangolin-CoV is the most closely related CoV to SARS-CoV-2. 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. We thank originating laboratories at South China Agricultural University (Y. Shen, L. Xiao and W. Chen; no. CAS 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. Stamatakis, A. RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models. Emerg. First, we took an approach that relies on identification of mosaic regions (via 3SEQ14 v.1.7) that are also supported by PI signals19. 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 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). Li, X. et al. It is clear from our analysis that viruses closely related to SARS-CoV-2 have been circulating in horseshoe bats for many decades. volume5,pages 14081417 (2020)Cite this article. However, the coronavirus isolated from pangolin is similar at 99% in a specific region of the S protein, which corresponds to the 74 amino acids involved in the ACE (Angiotensin Converting Enzyme . It allows a user to assign a SARS-CoV-2 genome sequence the most likely lineage (Pango lineage) to SARS-CoV-2 query sequences. Nat. 17, 15781579 (1999). In the absence of any reasonable prior knowledge on the TMRCA of the sarbecovirus datasets (which is required for grid specification in a skygrid model), we specified a simpler constant size population prior. Maciej F. Boni, Philippe Lemey, Andrew Rambaut or David L. Robertson. RegionB is 5,525nt long. Hu, B. et al. 2a. PubMed The Artic Network receives funding from the Wellcome Trust through project no. MERS-CoV data were subsampled to match sample sizes with SARS-CoV and HCoV-OC43. 53), this is inferred to have occurred before the divergence of RaTG13 and SARS-CoV-2 and thus should not influence our inferences. However, for several reasons, nucleotide sequences may be generated that cover only the spike gene of SARS-CoV-2. b, Similarity plot between SARS-CoV-2 and several selected sequences including RaTG13 (black), SARS-CoV (pink) and two pangolin sequences (orange). 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. 206298/Z/17/Z. PubMed Central 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). Lam, T. T. et al. Article & Bedford, T. MERS-CoV spillover at the camelhuman interface. There is a 90% DNA match between SARS CoV 2 and a coronavirus in pangolins. Nevertheless, the viral population is largely spatially structured according to provinces in the south and southeast on one lineage, and provinces in the centre, east and northeast on another (Fig. D.L.R. 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. 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. Evol. 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). Med. 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. Over relatively shallow timescales, such differences can primarily be explained by varying selective pressure, with mildly deleterious variants being eliminated more strongly by purifying selection over longer timescales44,45,46. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. 94, e0012720 (2020). Using these breakpoints, the longest putative non-recombining segment (nt1,88521,753) is 9.9kb long, and we call this region NRR2. 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. All four of these breakpoints were also identified with the tree-based recombination detection method GARD35. 3). Eden, J.-S., Tanaka, M. M., Boni, M. F., Rawlinson, W. D. & White, P. A. Recombination within the pandemic norovirus GII.4 lineage. 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 . RegionsB and C span nt3,6259,150 and 9,26111,795, respectively. Open reading frames are shown above the breakpoint plot, with the variable-loop region indicated in the Sprotein. We showed that severe acute respiratory syndrome coronavirus 2 is probably a novel recombinant virus. TMRCA estimates for SARS-CoV-2 and SARS-CoV from their respective most closely related bat lineages are reasonably consistent for the different data sets and different rate priors in our analyses. Nat. Coronavirus Disease 2019 (COVID-19) Situation Report 51 (World Health Organization, 2020). 1) and thus likely to be the product of recombination, acquiring a divergent variable loop from a hitherto unsampled bat sarbecovirus28. Nature 583, 282285 (2020). A phylogenetic treeusing RAxML v8.2.8 (ref. Another similarity between SARS-CoV and SARS-CoV-2 is their divergence time (4070years ago) from currently known extant bat virus lineages (Fig. 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. Li, Q. et al. 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. B.W.P. & Li, X. Crossspecies transmission of the newly identified coronavirus 2019nCoV. https://doi.org/10.1038/s41564-020-0771-4, DOI: https://doi.org/10.1038/s41564-020-0771-4. Discovery and genetic analysis of novel coronaviruses in least horseshoe bats in southwestern China. Lancet 395, 949950 (2020). PubMed Central In light of these time-dependent evolutionary rate dynamics, a slower rate is appropriate for calibration of the sarbecovirus evolutionary history. Martin, D. P., Murrell, B., Golden, M., Khoosal, A. Patino-Galindo, J. We compiled a dataset including 27human coronavirus OC43 virus genomes and ten related animal virus genomes (six bovine, three white-tailed deer and one canine virus). Two exceptions can be seen in the relatively close relationship of Hong Kong viruses to those from Zhejiang Province (with two of the latter, CoVZC45 and CoVZXC21, identified as recombinants) and a recombinant virus from Sichuan for which part of the genome (regionB of SC2018 in Fig. Wang, H., Pipes, L. & Nielsen, R. Synonymous mutations and the molecular evolution of SARS-Cov-2 origins. Complete genome sequence data were downloaded from GenBank and ViPR; accession numbers of all 68sequences are available in Supplementary Table 4. Microbiol. 3). eLife 7, e31257 (2018). Sequences are colour-coded by province according to the map. NTD, N-terminal domain; CTD, C-terminal domain. SARS-like WIV1-CoV poised for human emergence. The variable-loop region in SARS-CoV-2 shows closer identity to the 2019 pangolin coronavirus sequence than to the RaTG13 bat virus, supported by phylogenetic inference (Fig. Nguyen, L.-T., Schmidt, H. A., Von Haeseler, A. Phylogenies of subregions of NRR1 depict an appreciable degree of spatial structuring of the bat sarbecovirus population across different regions (Fig. This new approach classifies the newly sequenced genome against all the diverse lineages present instead of a representative select sequences. PureBasic 53 13 constellations Public Python 42 17 For the HCoV-OC43, MERS-CoV and SARS datasets we specified flexible skygrid coalescent tree priors. The red and blue boxplots represent the divergence time estimates for SARS-CoV-2 (red) and the 2002-2003 SARS-CoV (blue) from their most closely related bat virus, with the light- and dark-colored versions based on the HCoV-OC43 and MERS-CoV centered priors, respectively. Google Scholar. 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. J. Virol. is funded by the MRC (no. SARS-CoV-2 itself is not a recombinant of any sarbecoviruses detected to date, and its receptor-binding motif, important for specificity to human ACE2 receptors, appears to be an ancestral trait shared with bat viruses and not one acquired recently via recombination. In outbreaks of zoonotic pathogens, identification of the infection source is crucial because this may allow health authorities to separate human populations from the wildlife or domestic animal reservoirs posing the zoonotic risk9,10. https://doi.org/10.1093/molbev/msaa163 (2020). and JavaScript. Wan, Y., Shang, J., Graham, R., Baric, R. & Li, F. Receptor recognition by the novel Coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus. 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. Developed by the Centre for Genomic Pathogen Surveillance. stand-alone pangolin work flows or Illumina DRAGEN COVID Lineage App (v3.5.5) following the default parameters. Centre for Genomic Pathogen Surveillance. and D.L.R. Webster, R. G., Bean, W. J., Gorman, O. T., Chambers, T. M. & Kawaoka, Y. Evolution and ecology of influenza A viruses. 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. 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. The relatively fast evolutionary rate means that it is most appropriate to estimate shallow nodes in the sarbecovirus evolutionary history. 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. Curr. Add entries for pangolin-data/-assignment 1.18.1.1 (, Really add a document on testing strategy. RegionC showed no PI signals within it. The virus then. Cell 181, 223227 (2020). Natl Acad. master 4 branches 94 tags Code AngieHinrichs Add entries for pangolin-data/-assignment 1.18.1.1 ( #512) ad16752 4 days ago 990 commits .github/ workflows Update pangolin.yml 7 months ago docs docs need guide tree now 3 years ago pangolin 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 Nature 579, 270273 (2020). DRAGEN COVID Lineage App This app aligns reads to a SARS-CoV-2 reference genome and reports coverage of targeted regions. performed Srecombination analysis. Zhou, P. et al. Bioinformatics 30, 13121313 (2014). 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. 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. Extended Data Fig. . performed recombination and phylogenetic analysis and annotated virus names with geographical and sampling dates. 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. 110. 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. Alexandre Hassanin, Vuong Tan Tu, Gabor Csorba, Nicola F. Mller, Kathryn E. Kistler & Trevor Bedford, Jack M. Crook, Ivana Murphy, Diana Bell, Simon Pollett, Matthew A. Conte, Irina Maljkovic Berry, Yatish Turakhia, Bryan Thornlow, Russell Corbett-Detig, Nature Microbiology 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. According to GISAID . Effect of closure of live poultry markets on poultry-to-person transmission of avian influenza A H7N9 virus: an ecological study. and X.J. 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. =0.00025. 36)gives a putative recombination-free alignment that we call non-recombinant alignment3 (NRA3) (see Methods). Phylogenetic Assignment of Named Global Outbreak LINeages, The pangolin web app is maintained by the Centre for Genomic Pathogen Surveillance. Figure 1 (top) shows the distribution of all identified breakpoints (using 3SEQs exhaustive triplet search) by the number of candidate recombinant sequences supporting them. Biol. Wu, Y. et al. In early January, the aetiological agent of the pneumonia cases was found to be a coronavirus3, subsequently named SARS-CoV-2 by an International Committee on Taxonomy of Viruses (ICTV) Study Group4 and also named hCoV-19 by Wu et al.5. 25, 3548 (2017). We compiled a set of 69SARS-CoV genomes including 58 sampled from humans and 11 sampled from civets and raccoon dogs. 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. Publishers note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. The idea is that pangolins carrying the virus, SARS-CoV-2, came into contact with humans. 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 ). Virus Evol. Press, 2009). 36) (RDP, GENECONV, MaxChi, Bootscan, SisScan and 3SEQ) and considered recombination signals detected by more than two methods for breakpoint identification. 04:20. Syst. Sarbecovirus, HCoV-OC43 and SARS-CoV data were assembled from GenBank to be as complete as possible, with sampling year as an inclusion criterion. Evol. 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. 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.

Highland Cow Birthday Decorations, Articles P