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36, 7597 (2002). 5. Nature 538, 193200 (2016). All four of these breakpoints were also identified with the tree-based recombination detection method GARD35. Nguyen, L.-T., Schmidt, H. A., Von Haeseler, A. Accurate estimation of ages for deeper nodes would require adequate accommodation of time-dependent rate variation. Sci. Epidemiology, genetic recombination, and pathogenesis of coronaviruses. 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. performed Srecombination analysis. BEAGLE 3: improved performance, scaling, and usability for a high-performance computing library for statistical phylogenetics. The research leading to these results received funding (to A.R. Nature 579, 265269 (2020). Cov-Lineages While it is possible that pangolins, or another hitherto undiscovered species, may have acted as an intermediate host facilitating transmission to humans, current evidence is consistent with the virus having evolved in bats resulting in bat sarbecoviruses that can replicate in the upper respiratory tract of both humans and pangolins25,32. A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. Current sampling of pangolins does not implicate them as an intermediate host. 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. Originally, PANGOLIN used a maximum-likelihood-based assignment algorithm to assign query SARS-CoV-2 the most likely lineage sequence. PubMed The time-calibrated phylogeny represents a maximum clade credibility tree inferred for NRR1. BEAST inferences made use of the BEAGLE v.3 library68 for efficient likelihood computations. 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. We focused on these three non-recombining regions/alignments for divergence time estimation; this avoids inappropriate modelling of evolutionary processes with recombination on strictly bifurcating trees, which can result in different artefacts such as homoplasies that inflate branch lengths and lead to apparently longer evolutionary divergence times. and D.L.R. stand-alone pangolin work flows or Illumina DRAGEN COVID Lineage App (v3.5.5) following the default parameters. You signed in with another tab or window. Extended Data Fig. Bioinformatics 30, 13121313 (2014). Boxes show 95% HPD credible intervals. 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. Use the Previous and Next buttons to navigate the slides or the slide controller buttons at the end to navigate through each slide. Its origin and direct ancestral viruses have not been . 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. However, on closer inspection, the relative divergences in the phylogenetic tree (Fig. 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. performed recombination and phylogenetic analysis and annotated virus names with geographical and sampling dates. Are pangolins the intermediate host of the 2019 novel coronavirus (SARS-CoV-2)? wrote the first draft of the manuscript, and all authors contributed to manuscript editing. 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. Hu, B. et al. The lineage B.1 has been the major basal and widespread lineage from the initial SARS-CoV-2 spread and it became the more prevalent lineage in Colombia ( 13 ), while the B.1.111 lineage, first detected in the USA from a sample collected on March 7, 2020 and subsequently in Colombia on March 13, 2020 is currently circulating and mainly represented Because the estimated rates and divergence dates were highly similar in the three datasets analysed, we conclude that our estimates are robust to the method of identifying a genomes NRRs. Future trajectory of SARS-CoV-2: Constant spillover back and forth The command line tool is open source software available under the GNU General Public License v3.0. In this study, we report the case of a child with severe combined immu presenting a prolonged severe acute respiratory syndrome coronavirus 2 infection. Maciej F. Boni, Philippe Lemey, Andrew Rambaut or David L. Robertson. and X.J. Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage responsible for the COVID-19 pandemic, https://doi.org/10.1038/s41564-020-0771-4. 874850). 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. Graham, R. L. & Baric, R. S. Recombination, reservoirs, and the modular spike: mechanisms of coronavirus cross-species transmission. Viruses 11, 979 (2019). PDF How COVID-19 Variants Get Their Name - doh.wa.gov The idea is that pangolins carrying the virus, SARS-CoV-2, came into contact with humans. & Holmes, E. C. Recombination in evolutionary genomics. Based on the identified breakpoints in each genome, only the major non-recombinant region is kept in each genome while other regions are masked. Wong, A. C. P., Li, X., Lau, S. K. P. & Woo, P. C. Y. a, Breakpoints identified by 3SEQ illustrated by percentage of sequences (out of 68) that support a particular breakpoint position. In case of DRAGEN COVID Lineage tool, the minimum accepted alignment score was set to 22 and results with scores <22 were discarded. Since the release of Version 2.0 in July 2020, however, it has used the 'pangoLEARN' machine-learning-based assignment algorithm to assign lineages to new SARS-CoV-2 genomes. Yuan, J. et al. We thank originating laboratories at South China Agricultural University (Y. Shen, L. Xiao and W. Chen; no. 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. Eden, J.-S., Tanaka, M. M., Boni, M. F., Rawlinson, W. D. & White, P. A. Recombination within the pandemic norovirus GII.4 lineage. Using the most conservative approach to identification of a non-recombinant genomic region (NRR1), SARS-CoV-2 forms a sister lineage with RaTG13, with genetically related cousin lineages of coronavirus sampled in pangolins in Guangdong and Guangxi provinces (Fig. is funded by The National Natural Science Foundation of China Excellent Young Scientists Fund (Hong Kong and Macau; no. Global epidemiology of bat coronaviruses. Boxplots show interquartile ranges, white lines are medians and box whiskers show the full range of posterior distribution. Schierup, M. H. & Hein, J. Recombination and the molecular clock. Virus Evol. GitHub - cov-lineages/pangolin: Software package for assigning SARS-CoV-2 genome sequences to global lineages. Green boxplots show the TMRCA estimate for the RaTG13/SARS-CoV-2 lineage and its most closely related pangolin lineage (Guangdong 2019). 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. The origins we present in Fig. M.F.B. 3). Extended Data Fig. We thank A. Chan and A. Irving for helpful comments on the manuscript. Lond. While there is evidence of positive selection in the sarbecovirus lineage leading to RaTG13/SARS-CoV-2 (ref. Here, we analyse the evolutionary history of SARS-CoV-2 using available genomic data on sarbecoviruses. 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). 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. These authors contributed equally: Maciej F. Boni, Philippe Lemey. 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 Ge, X. et al. Adv. Transparent bands of interquartile range width and with the same colours are superimposed to highlight the overlap between estimates. COVID-19: A Catastrophe or Opportunity for Pangolin Conservation? - Nature 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. PubMed 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. Conducting analogous analyses of codon usage bias as Ji et al. 26, 450452 (2020). Nat. CAS 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. Allen O'Brien on LinkedIn: #r #rstudio #rstats #pangolin #covid19 # Dis. is funded by the MRC (no. 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 (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. the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Methods Ecol. 68, 10521061 (2019). 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. SARS-CoV-2 genetic lineages in the United States are routinely monitored through epidemiological investigations, virus genetic sequence-based surveillance, and laboratory studies. [12] A reduced sequence set of 25sequences chosen to capture the breadth of diversity in the sarbecoviruses (obvious recombinants not involving the SARS-CoV-2 lineage were also excluded) was used because GARD is computationally intensive. 56, 152179 (1992). A distinct name is needed for the new coronavirus. The key to successful surveillance is knowing which viruses to look for and prioritizing those that can readily infect humans47. 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. Pangolin-CoV is 91.02% and 90.55% identical to SARS-CoV-2 and BatCoV RaTG13, respectively, at the whole-genome level. 6, e14 (2017). Menachery, V. D. et al. All authors contributed to analyses and interpretations. Sequence similarity. J. Gen. Virol. Coronavirus Disease 2019 (COVID-19) Situation Report 51 (World Health Organization, 2020). Mol. & Bedford, T. MERS-CoV spillover at the camelhuman interface. To obtain 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). R. Soc. Nature 583, 282285 (2020). A tag already exists with the provided branch name. Bruen, T. C., Philippe, H. & Bryant, D. A simple and robust statistical test for detecting the presence of recombination. & Holmes, E. C. A genomic perspective on the origin and emergence of SARS-CoV-2. Possible Bat Origin of Severe Acute Respiratory Syndrome Coronavirus 2 A., Lytras, S., Singer, J. eLife 7, e31257 (2018). Pangolins may have incubated the novel coronavirus, gene study shows Unfortunately, a response that would achieve containment was not possible. We considered (1) the possibility that BFRs could be combined into larger non-recombinant regions and (2) the possibility of further recombination within each BFR. Pangolin was developed to implement the dynamic nomenclature of SARS-CoV-2 lineages, known as the Pango nomenclature. Open reading frames are shown above the breakpoint plot, with the variable-loop region indicated in the Sprotein. 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 Slider with three articles shown per slide. Stegeman, A. et al. PLoS Pathog. It is available as a command line tool and a web application. As illustrated by the dashed arrows, these two posteriors motivate our specification of prior distributions with standard deviations inflated 10-fold (light color). The histogram allows for the identification of non-recombining regions (NRRs) by revealing regions with no breakpoints. Evol. 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. The canine viral genome was excluded from the Bayesian phylogenetic analyses because temporal signal analyses (see below) indicated that it was an outlier. 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). J. Virol. Given that these pangolin viruses are ancestral to the progenitor of the RaTG13/SARS-CoV-2 lineage, it is more likely that they are also acquiring viruses from bats. . A new SARS-CoV-2 variant (B.1.1.523) capable of escaping immune protections The coverage threshold and consensus sequence generation threshold were set to 20 and 90 respectively. Provided by the Springer Nature SharedIt content-sharing initiative, Molecular and Cellular Biochemistry (2023), Nature Microbiology (Nat 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 ). 27) receptors and its RBD being genetically closer to a pangolin virus than to RaTG13 (refs. However, formal testing using marginal likelihood estimation41 does provide some evidence of a temporal signal, albeit with limited log Bayes factor support of 3 (NRR1), 10 (NRR2) and 3 (NRA3); see Supplementary Table 1. The assumption of long-term purifying selection would imply that coronaviruses are in endemic equilibrium with their natural host species, horseshoe bats, to which they are presumably well adapted. Holmes, E. C., Dudas, G., Rambaut, A. Press, H.) 3964 (Springer, 2009). Our most conservative approach attempted to ensure that putative NRRs had no mosaic or phylogenetic incongruence signals. To begin characterizing any ancestral relationships for SARS-CoV-2, NRRs of the genome must be identified so that reliable phylogenetic reconstruction and dating can be performed. PLoS Pathog. Note that breakpoints can be shared between sequences if they are descendants of the same recombination events. Nucleotide positions for phylogenetic inference are 147695, 9621,686 (first tree), 3,6259,150 (second tree, also BFR B), 9,26111,795 (third tree, also BFR C), 12,44319,638 (fourth tree) and 23,63124,633, 24,79525,847, 27,70228,843 and 29,57430,650 (fifth tree). 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. There is a 90% DNA match between SARS CoV 2 and a coronavirus in pangolins. All sequence data analysed in this manuscript are available at https://github.com/plemey/SARSCoV2origins. Med. 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)). Natl Acad. Correspondence to 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 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. 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.