All three approaches to removal of recombinant genomic segments point to a single ancestral lineage for SARS-CoV-2 and RaTG13. 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. 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). Preprint at https://doi.org/10.1101/2020.04.20.052019 (2020). Discovery and genetic analysis of novel coronaviruses in least horseshoe bats in southwestern China. Given what was known about the origins of SARS, as well as identification of SARS-like viruses circulating in bats that had binding sites adapted to human receptors29,30,31, appropriate measures should have been in place for immediate control of outbreaks of novel coronaviruses. 31922087). Eight other BFRs <500nt were identified, and the regions were named BFRAJ in order of length. Aiewsakun, P. & Katzourakis, A. Time-dependent rate phenomenon in viruses. 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 . 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 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. 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). Region A has been shortened to A (5,017nt) based on potential recombination signals within the region. 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. & Holmes, E. C. Recombination in evolutionary genomics. 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. Uncertainty measures are shown in Extended Data Fig. 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. 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. Correspondence to Webster, R. G., Bean, W. J., Gorman, O. T., Chambers, T. M. & Kawaoka, Y. Evolution and ecology of influenza A viruses. These authors contributed equally: Maciej F. Boni, Philippe Lemey. 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. acknowledges support by the Research FoundationFlanders (Fonds voor Wetenschappelijk OnderzoekVlaanderen (nos. Virological.org http://virological.org/t/ncov-2019-codon-usage-and-reservoir-not-snakes-v2/339 (2020). collected SARS-CoV data and assisted in analyses of SARS-CoV and SARS-CoV-2 data. 87, 62706282 (2013). the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Nguyen, L.-T., Schmidt, H. A., Von Haeseler, A. 4), but also by markedly different evolutionary rates. Stamatakis, A. RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. A.R. As of December 2, 2021, SJdRP, a medium-sized city in the Northwest region of So Paulo state, Brazil (Fig. Preprint at https://doi.org/10.1101/2020.02.10.942748 (2020). 1) and thus likely to be the product of recombination, acquiring a divergent variable loop from a hitherto unsampled bat sarbecovirus28. 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. He, B. et al. Stamatakis, A. RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models. The Pango dynamic nomenclature is a popular system for classifying and naming genetically-distinct lineages of SARS-CoV-2, including variants of concern, and is based on the analysis of complete or near-complete virus genomes. 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. Are you sure you want to create this branch? It is RaTG13 that is more divergent in the variable-loop region (Extended Data Fig. Wong, A. C. P., Li, X., Lau, S. K. P. & Woo, P. C. Y. 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. A distinct name is needed for the new coronavirus. 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. 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. 206298/Z/17/Z. Genetics 172, 26652681 (2006). Mol. 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. 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). Google Scholar. Viruses 11, 979 (2019). PureBasic 53 13 constellations Public Python 42 17 Grey tips correspond to bat viruses, green to pangolin, blue to SARS-CoV and red to SARS-CoV-2. 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 . Evol. PLoS ONE 5, e10434 (2010). Many Git commands accept both tag and branch names, so creating this branch may cause unexpected behavior. Li, Q. et al. Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus. The S1 protein of Pangolin-CoV is much more closely related to SARS-CoV-2 than to RaTG13. By 2009, however, rapid genomic analysis had become a routine component of outbreak response. Sequences are colour-coded by province according to the map. J. Infect. The key to successful surveillance is knowing which viruses to look for and prioritizing those that can readily infect humans47. 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. 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 The coronavirus genome that these researchers had assembled, from pangolin lung-tissue samples, contained some gene regions that were ninety-nine per cent similar to equivalent parts of the SARS . performed recombination analysis for non-recombining alignment3, calibration of rate of evolution and phylogenetic reconstruction and dating. 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. Bryant, D. & Moulton, V. Neighbor-Net: an agglomerative method for the construction of phylogenetic networks. 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). 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. Humans' selfish, speciesist treatment of these animals could be the very reason why the novel coronavirus exists. & Andersen, K. G. Pandemics: spend on surveillance, not prediction. Zhang, Y.-Z. Share . # 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 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. B 281, 20140732 (2014). 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 . Wu, F. 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. Boxplots show interquartile ranges, white lines are medians and box whiskers show the full range of posterior distribution. 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). & Andersen, K. G. The evolution of Ebola virus: insights from the 20132016 epidemic. A third approach attempted to minimize the number of regions removed while also minimizing signals of mosaicism and homoplasy. 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. performed recombination analysis for non-recombining regions1 and 2, breakpoint analysis and phylogenetic inference on recombinant segments. To avoid artefacts due to recombination, we focused on NRR1 and NRR2 and the recombination-masked alignment NRA3 to infer time-measured evolutionary histories. 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. Visual exploration using TempEst39 indicates that there is no evidence for temporal signal in these datasets (Extended Data Fig. In March, when covid cases began spiking around India, Bani Jolly went hunting for answers in the virus's genetic code. USA 113, 30483053 (2016). The histogram allows for the identification of non-recombining regions (NRRs) by revealing regions with no breakpoints. The first available sequence data6 placed this novel human pathogen in the Sarbecovirus subgenus of Coronaviridae7, the same subgenus as the SARS virus that caused a global outbreak of >8,000 cases in 20022003. Coronavirus: Pangolins found to carry related strains. Originally, PANGOLIN used a maximum-likelihood-based assignment algorithm to assign query SARS-CoV-2 the most likely lineage sequence. Maciej F. Boni, Philippe Lemey, Andrew Rambaut or David L. Robertson. Mol. Publishers note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. 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. 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. Google Scholar. 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 . 2). Biol. The genetic distances between SARS-CoV-2 and RaTG13 (bottom) demonstrate that their relationship is consistent across all regions except for the variable loop. 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. J. Virol. Unfortunately, a response that would achieve containment was not possible. The relatively fast evolutionary rate means that it is most appropriate to estimate shallow nodes in the sarbecovirus evolutionary history. Forni, D., Cagliani, R., Clerici, M. & Sironi, M. Molecular evolution of human coronavirus genomes. Extended Data Fig. 36)gives a putative recombination-free alignment that we call non-recombinant alignment3 (NRA3) (see Methods). 36, 7597 (2002). The divergence time estimates for SARS-CoV-2 and SARS-CoV from their respective most closely related bat lineages are reasonably consistent among the three approaches we use to eliminate the effects of recombination in the alignment. Microbes Infect. In the meantime, to ensure continued support, we are displaying the site without styles A., Filip, I., AlQuraishi, M. & Rabadan, R. Recombination and lineage-specific mutations led to the emergence of SARS-CoV-2. 82, 48074811 (2008). Because these subclades had different phylogenetic relationships in regionD (Supplementary Fig. Virus Evol. Lam, H. M., Ratmann, O. PubMed Evol. & Holmes, E. C. A genomic perspective on the origin and emergence of SARS-CoV-2. 5). Bioinformatics 28, 32483256 (2012). All sequence data analysed in this manuscript are available at https://github.com/plemey/SARSCoV2origins. Conducting analogous analyses of codon usage bias as Ji et al. 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. CAS Wang, H., Pipes, L. & Nielsen, R. Synonymous mutations and the molecular evolution of SARS-Cov-2 origins. Google Scholar. 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 6, eabb9153 (2020). 13, e1006698 (2017). Lie, P., Chen, W. & Chen, J.-P. For weather, science, and COVID-19 . Virus Evol. Ji, W., Wang, W., Zhao, X., Zai, J. Nature 538, 193200 (2016). Intraspecies diversity of SARS-like coronaviruses in Rhinolophus sinicus and its implications for the origin of SARS coronaviruses in humans. wrote the first draft of the manuscript, and all authors contributed to manuscript editing. These rate priors are subsequently used in the Bayesian inference of posterior rates for NRR1, NRR2, and NRA3 as indicated by the solid arrows. https://doi.org/10.1093/molbev/msaa163 (2020). 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 725422-ReservoirDOCS). 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. Open reading frames are shown above the breakpoint plot, with the variable-loop region indicated in the Sprotein. Press, 2009). =0.00025. Divergence time estimates based on the three regions/alignments where the effects of recombination have been removed. A phylogenetic treeusing RAxML v8.2.8 (ref. This statement informs us of the possibility that a virus has spilled over from a very rare and shy reptile-looking mammal . Sci. The command line tool is open source software available under the GNU General Public License v3.0. with an alignment on which an initial recombination analysis was done. Mol. J. Virol. 3). J. Virol. 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 . Using these breakpoints, the longest putative non-recombining segment (nt1,88521,753) is 9.9kb long, and we call this region NRR2. The SARS-CoV divergence times are somewhat earlier than dates previously estimated15 because previous estimates were obtained using a collection of SARS-CoV genomes from human and civet hosts (as well as a few closely related bat genomes), which implies that evolutionary rates were predominantly informed by the short-term SARS outbreak scale and probably biased upwards. 5. To employ phylogenetic dating methods, recombinant regions of a 68-genome sarbecovirus alignment were removed with three independent methods. Slider with three articles shown per slide. Lancet 395, 565574 (2020). =0.00075 and one with a mean of 0.00024 and s.d. Sign up for the Nature Briefing newsletter what matters in science, free to your inbox daily. 21, 255265 (2004). 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. D.L.R. A tag already exists with the provided branch name. 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). 23, 18911901 (2006). In Extended Data Fig. A new coronavirus associated with human respiratory disease in China. Rambaut, A., Lam, T. T., Carvalho, L. M. & Pybus, O. G. Exploring the temporal structure of heterochronous sequences using TempEst (formerly Path-O-Gen). Add entries for pangolin-data/-assignment 1.18.1.1 (, Really add a document on testing strategy. 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. 5 (NRR1) are conservative in the sense that NRR1 is more likely to be non-recombinant than NRR2 or NRA3. 32, 268274 (2014). 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. 21, 15081514 (2015). 27) receptors and its RBD being genetically closer to a pangolin virus than to RaTG13 (refs. 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. 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. Membrebe, J. V., Suchard, M. A., Rambaut, A., Baele, G. & Lemey, P. Bayesian inference of evolutionary histories under time-dependent substitution rates. 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). Martin, D. P., Murrell, B., Golden, M., Khoosal, A. It compares the new genome against the large, diverse population of sequenced strains using a Annu Rev. DRAGEN COVID Lineage App This app aligns reads to a SARS-CoV-2 reference genome and reports coverage of targeted regions. 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. & Muhire, B. RDP4: Detection and analysis of recombination patterns in virus genomes. Note that breakpoints can be shared between sequences if they are descendants of the same recombination events. performed Srecombination analysis. Split diversity in constrained conservation prioritization using integer linear programming. 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. One geographic clade includes viruses from provinces in southern China (Guangxi, Yunnan, Guizhou and Guangdong), with its major sister clade consisting of viruses from provinces in northern China (Shanxi, Henan, Hebei and Jilin) as well as Hubei Province in central China and Shaanxi Province in northwestern China. 1, vev003 (2015). 190, 20882095 (2004). Su, S. et al. Curr. 04:20. 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). A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. While there is involvement of other mammalian speciesspecifically pangolins for SARS-CoV-2as a plausible conduit for transmission to humans, there is no evidence that pangolins are facilitating adaptation to humans. 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. PLoS Pathog. Abstract. performed recombination and phylogenetic analysis and annotated virus names with geographical and sampling dates. Our third approach involved identifying breakpoints and masking minor recombinant regions (with gaps, which are treated as unobserved characters in probabilistic phylogenetic approaches). Zhou, H. et al. Biol. The inset represents divergence time estimates based on NRR1, NRR2 and NRA3. 17, 15781579 (1999). Concatenated region ABC is NRR1. Boxes show 95% HPD credible intervals. Even before the COVID-19 pandemic, pangolins have been making headlines. Trends Microbiol. 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. All custom code used in the manuscript is available at https://github.com/plemey/SARSCoV2origins. J. Virol. The virus then. The sizes of the black internal node circles are proportional to the posterior node support. 3). 92, 433440 (2020). Dis. Suchard, M. A. et al. Due to the absence of temporal signal in the sarbecovirus datasets, we used informative prior distributions on the evolutionary rate to estimate divergence dates. All authors contributed to analyses and interpretations. Extended Data Fig. SARS-CoV-2 is an appropriate name for the new coronavirus. and T.A.C. J. Virol. A deep dive into the genetics of the novel coronavirus shows it seems to have spent some time infecting both bats and pangolins before it jumped into humans, researchers said . PubMed We thank all authors who have kindly deposited and shared genome data on GISAID. Liu, P. et al. 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. Internet Explorer). (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. Biol. "This is an extremely interesting . Phylogenetic trees and exact breakpoints for all ten BFRs are shown in Supplementary Figs. We aimed to analyze 3 naso-oropharyngeal swab samples collected between August and December 2021 to describe the amino acid changes present in the sequence reads that may have a role in the emergence of new . Mol. All four of these breakpoints were also identified with the tree-based recombination detection method GARD35. Because 3SEQ identified ten BFRs >500nt, we used GARDs (v.2.5.0) inference on 10, 11 and 12 breakpoints. 110. Based on the identified breakpoints in each genome, only the major non-recombinant region is kept in each genome while other regions are masked. We used TreeAnnotator to summarize posterior tree distributions and annotated the estimated values to a maximum clade credibility tree, which was visualized using FigTree. Lancet 383, 541548 (2013). Syst. 3) clusters with viruses from provinces in the centre, east and northeast of China. The boxplots show divergence time estimates (posterior medians) for SARS-CoV-2 (red) and the 20022003 SARS-CoV virus (blue) from their most closely related bat virus. PubMed 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 5. 36) (RDP, GENECONV, MaxChi, Bootscan, SisScan and 3SEQ) and considered recombination signals detected by more than two methods for breakpoint identification. Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins. Specifically, progenitors of the RaTG13/SARS-CoV-2 lineage appear to have recombined with the Hong Kong clade (with inferred breakpoints at 11.9 and 20.8kb) to form the CoVZXC21/CoVZC45-lineage. SARS-CoV-2 and RaTG13 are also exceptions because they were sampled from Hubei and Yunnan, respectively. A pneumonia outbreak associated with a new coronavirus of probable bat origin. 82, 18191826 (2008). 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 . PubMedGoogle Scholar. Microbiol. 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. BEAST inferences made use of the BEAGLE v.3 library68 for efficient likelihood computations. 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 .
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