pangolin lineage covid
These rate priors are subsequently used in the Bayesian inference of posterior rates for NRR1, NRR2, and NRA3 as indicated by the solid arrows. Bruen, T. C., Philippe, H. & Bryant, D. A simple and robust statistical test for detecting the presence of recombination. Evol. 94, e0012720 (2020). 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. MC_UU_1201412). Current sampling of pangolins does not implicate them as an intermediate host. 26, 450452 (2020). 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. Unlike other viruses that have emerged in the past two decades, coronaviruses are highly recombinogenic14,15,16. In case of DRAGEN COVID Lineage tool, the minimum accepted alignment score was set to 22 and results with scores <22 were discarded. It is clear from our analysis that viruses closely related to SARS-CoV-2 have been circulating in horseshoe bats for many decades. Extended Data Fig. 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. The key to successful surveillance is knowing which viruses to look for and prioritizing those that can readily infect humans47. 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. Rambaut, A., Lam, T. T., Carvalho, L. M. & Pybus, O. G. Exploring the temporal structure of heterochronous sequences using TempEst (formerly Path-O-Gen). 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. 3). 190, 20882095 (2004). 1 Phylogenetic relationships in the C-terminal domain (CTD). 5. Viruses 11, 174 (2019). Phylogenetic trees and exact breakpoints for all ten BFRs are shown in Supplementary Figs. 35, 247251 (2018). Wang, L. et al. & Minh, B. Q. IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies. G066215N, G0D5117N and G0B9317N)) and by the European Unions Horizon 2020 project MOOD (no. b, Similarity plot between SARS-CoV-2 and several selected sequences including RaTG13 (black), SARS-CoV (pink) and two pangolin sequences (orange). Unfortunately, a response that would achieve containment was not possible. We thank all authors who have kindly deposited and shared genome data on GISAID. Chernomor, O. et al. Originally, PANGOLIN used a maximum-likelihood-based assignment algorithm to assign query SARS-CoV-2 the most likely lineage sequence. 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. Biol. However, for several reasons, nucleotide sequences may be generated that cover only the spike gene of SARS-CoV-2. 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 genome sequences. 2). 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. Lam, T. T. et al. Natl Acad. 16, e1008421 (2020). & Muhire, B. RDP4: Detection and analysis of recombination patterns in virus genomes. Forni, D., Cagliani, R., Clerici, M. & Sironi, M. Molecular evolution of human coronavirus genomes. Preprint at https://doi.org/10.1101/2020.04.20.052019 (2020). Evol. 5, 536544 (2020). (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). 1c). In Extended Data Fig. 4. 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. 62,63), the GTR+ model and 100bootstrap replicateswas inferred for each BFR >500nt. 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. The histogram allows for the identification of non-recombining regions (NRRs) by revealing regions with no breakpoints. Holmes, E. C., Dudas, G., Rambaut, A. 2). It compares the new genome against the large, diverse population of sequenced strains using a Anderson, K. G. nCoV-2019 codon usage and reservoir (not snakes v2). 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. Syst. 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. 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 Patino-Galindo, J. By 2009, however, rapid genomic analysis had become a routine component of outbreak response. CAS Stamatakis, A. RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models. J. Virol. 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. Wong, A. C. P., Li, X., Lau, S. K. P. & Woo, P. C. Y. P.L. 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. Extended Data Fig. It is available as a command line tool and a web application. 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. 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. 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). Are you sure you want to create this branch? Extended Data Fig. 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 After removal of A1 and A4, we named the new region A. 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. Microbiol. But some theories suggest that pangolins may be the source of the novel coronavirus. Virus Evol. PubMed Central This leaves the insertion of polybasic. 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. Trends Microbiol. 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 ). Because 3SEQ identified ten BFRs >500nt, we used GARDs (v.2.5.0) inference on 10, 11 and 12 breakpoints. J. Gen. Virol. Yu, H. et al. 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. 95% credible interval bars are shown for all internal node ages. 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. Hon, C. et al. Press, H.) 3964 (Springer, 2009). Preprint at https://doi.org/10.1101/2020.05.28.122366 (2020). 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. 1, vev003 (2015). Developed by the Centre for Genomic Pathogen Surveillance. 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. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. The virus then. This is not surprising for diverse viral populations with relatively deep evolutionary histories. A phylogenetic treeusing RAxML v8.2.8 (ref. It is RaTG13 that is more divergent in the variable-loop region (Extended Data Fig. Slider with three articles shown per slide. 24, 490502 (2016). 1a-c ), has the third-highest number of confirmed COVID-19 cases in the state of So. If the latter still identified non-negligible recombination signal, we removed additional genomes that were identified as major contributors to the remaining signal. Nature 503, 535538 (2013). Host ecology determines the dispersal patterns of a plant virus. J. Virol. Lancet 395, 565574 (2020). In our analyses of the sarbecovirus datasets, we incorporated the uncertainty of the sampling dates when exact dates were not available. USA 113, 30483053 (2016). 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). There is a 90% DNA match between SARS CoV 2 and a coronavirus in pangolins. Internet Explorer). Biol. PubMed 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. Zhang, Y.-Z. 3). 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. Our third approach involved identifying breakpoints and masking minor recombinant regions (with gaps, which are treated as unobserved characters in probabilistic phylogenetic approaches). Our approach resulted in similar posterior rates using two different prior means, implying that the sarbecovirus data do inform the rate estimate even though a root-to-tip temporal signal was not apparent. 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). Proc. Specifically, using a formal Bayesian approach42 (see Methods), we estimate a fast evolutionary rate (0.00169 substitutions per siteyr1, 95% highest posterior density (HPD) interval (0.00131,0.00205)) for SARS viruses sampled over a limited timescale (1year), a slower rate (0.00078 (0.00063,0.00092) substitutions per siteyr1) for MERS-CoV on a timescale of about 4years and the slowest rate (0.00024 (0.00019,0.00029) substitutions per siteyr1) for HCoV-OC43 over almost five decades. Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage responsible for the COVID-19 pandemic. To estimate non-synonymous over synonymous rate ratios for the concatenated coding genes, we used the empirical Bayes Renaissance countingprocedure67. 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 3). A.R. a, Breakpoints identified by 3SEQ illustrated by percentage of sequences (out of 68) that support a particular breakpoint position. Bioinformatics 22, 26882690 (2006). wrote the first draft of the manuscript, and all authors contributed to manuscript editing. Next, we (1) collected all breakpoints into a single set, (2) complemented this set to generate a set of non-breakpoints, (3) grouped non-breakpoints into contiguous BFRs and (4) sorted these regions by length. Nat Microbiol 5, 14081417 (2020). 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. Nature 579, 265269 (2020). 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. Regions AC were further examined for mosaic signals by 3SEQ, and all showed signs of mosaicism. NTD, N-terminal domain; CTD, C-terminal domain. Background & objectives: Several phylogenetic classification systems have been devised to trace the viral lineages of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). & Andersen, K. G. Pandemics: spend on surveillance, not prediction. 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). 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. 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. & Andersen, K. G. The evolution of Ebola virus: insights from the 20132016 epidemic. Region A has been shortened to A (5,017nt) based on potential recombination signals within the region. and JavaScript. # File containing the ID of the samples, the Sequence of the haplotype, the Continent, the country, the Region, the Data, the Lineage of Pangolin and Nextstrain clade, and the haplotype number # In this order # Could be obtained from the database 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). GitHub - cov-lineages/pangolin: Software package for assigning SARS-CoV-2 genome sequences to global lineages. 2 Lack of root-to-tip temporal signal in SARS-CoV-2. To avoid artefacts due to recombination, we focused on NRR1 and NRR2 and the recombination-masked alignment NRA3 to infer time-measured evolutionary histories. 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). Viruses 11, 979 (2019). 23, 18911901 (2006). We extracted a total of 2189 full-length SARS-CoV-2 viral genomes from various states of India from the EpiCov repository of the GISAID initiative on 12 June 2020. Publishers note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. However, inconsistency in the nomenclature limits uniformity in its epidemiological understanding. 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. The idea is that pangolins carrying the virus, SARS-CoV-2, came into contact with humans. Effect of closure of live poultry markets on poultry-to-person transmission of avian influenza A H7N9 virus: an ecological study. 2). Holmes, E. C. The Evolution and Emergence of RNA Viruses (Oxford Univ. Mol. Using these breakpoints, the longest putative non-recombining segment (nt1,88521,753) is 9.9kb long, and we call this region NRR2. Biol. All authors contributed to analyses and interpretations. M.F.B. Biol. Emerg. 68, 10521061 (2019). 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. However, on closer inspection, the relative divergences in the phylogenetic tree (Fig. Our results indicate the presence of a single lineage circulating in bats with properties that allowed it to infect human cells, as previously described for bat sarbecoviruses related to the first SARS-CoV lineage29,30,31. Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor. Lu, R. et al. Google Scholar. Genetic lineages of SARS-CoV-2 have been emerging and circulating around the world since the beginning of the COVID-19 pandemic. Bayesian phylogenetic and phylodynamic data integration using BEAST 1.10. Yuan, J. et al. Conservatively, we combined the three BFRs >2kb identified above into non-recombining region1 (NRR1). SARS-like WIV1-CoV poised for human emergence. Viral metagenomics revealed Sendai virus and coronavirus infection of Malayan pangolins (Manis javanica). the development of viral diversity. 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. All three approaches to removal of recombinant genomic segments point to a single ancestral lineage for SARS-CoV-2 and RaTG13. 5). Indeed, the rates reported by these studies are in line with the short-term SARS rates that we estimate (Fig. Bryant, D. & Moulton, V. Neighbor-Net: an agglomerative method for the construction of phylogenetic networks. 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). Our most conservative approach attempted to ensure that putative NRRs had no mosaic or phylogenetic incongruence signals. The origins we present in Fig. A novel bat coronavirus closely related to SARS-CoV-2 contains natural insertions at the S1/S2 cleavage site of the Spike protein. 2a. It allows a user to assign a SARS-CoV-2 genome sequence the most likely lineage (Pango lineage) to SARS-CoV-2 query sequences. Virological.org http://virological.org/t/ncov-2019-codon-usage-and-reservoir-not-snakes-v2/339 (2020). Zhou, H. et al. Suchard, M. A. et al. For weather, science, and COVID-19 . Anderson, K. G., Rambaut, A., Lipkin, W. I., Holmes, E. C. & Garry, R. F. The proximal origin of SARS-CoV-2. The plots are based on maximum likelihood tree reconstructions with a root position that maximises the residual mean squared for the regression of root-to-tip divergence and sampling time. B 281, 20140732 (2014). 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)). 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. Proc. is funded by The National Natural Science Foundation of China Excellent Young Scientists Fund (Hong Kong and Macau; no. This commit does not belong to any branch on this repository, and may belong to a fork outside of the repository. Nature 579, 270273 (2020). 90, 71847195 (2016). 5 Comparisons of GC content across taxa. stand-alone pangolin work flows or Illumina DRAGEN COVID Lineage App (v3.5.5) following the default parameters. Zhou, P. et al. DRAGEN COVID Lineage App This app aligns reads to a SARS-CoV-2 reference genome and reports coverage of targeted regions. Bayesian evaluation of temporal signal in measurably evolving populations.
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