We extracted a similar number (n=35) of genomes from a MERS-CoV dataset analysed by Dudas et al.59 using the phylogenetic diversity analyser tool60 (v.0.5). PLoS Pathog. 725422-ReservoirDOCS). 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. 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. Identification of diverse alphacoronaviruses and genomic characterization of a novel severe acute respiratory syndrome-like coronavirus from bats in China. covid19_mostefai2021_paper/01_CreateObjects.r at master HussinLab Wang, L. et al. 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). 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). Two other bat viruses (CoVZXC21 and CoVZC45) from Zhejiang Province fall on this lineage as recombinants of the RaTG13/SARS-CoV-2 lineage and the clade of Hong Kong bat viruses sampled between 2005 and 2007 (Fig. At present, we analyzed the diversity of SARS-CoV-2 viral genomes in India to know the evolutionary patterns of viruses in the country through their pangolin lineage and GISAID-Clade. 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. 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. volume5,pages 14081417 (2020)Cite this article. 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. Google Scholar. Cell 181, 223227 (2020). Indeed, the rates reported by these studies are in line with the short-term SARS rates that we estimate (Fig. Viral metagenomics revealed Sendai virus and coronavirus infection of Malayan pangolins (Manis javanica). and D.L.R. Identifying SARS-CoV-2 related coronaviruses in Malayan pangolins Li, Q. et al. A., Lytras, S., Singer, J. 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 . Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage - Nature Phylogenies of subregions of NRR1 depict an appreciable degree of spatial structuring of the bat sarbecovirus population across different regions (Fig. Biol. PubMedGoogle Scholar. COVID-19: Time to exonerate the pangolin from the transmission of SARS 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. 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). Proc. Evol. Identifying SARS-CoV-2-related coronaviruses in Malayan pangolins Zhou, P. et al. Complete genome sequence data were downloaded from GenBank and ViPR; accession numbers of all 68sequences are available in Supplementary Table 4. 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 . =0.00025. Lu, R. et al. Note that six of these sequences fall under the terms of use of the GISAID platform. Instead, similarity in codon usage metrics between the SARS-CoV-2 and eukaryotes analyzed was correlated with coding sequence GC content of the eukaryote, with more similar codon usage being identified in eukaryotes with low GC content similar to that of the coronavirus (b). There is a 90% DNA match between SARS CoV 2 and a coronavirus in pangolins. Are you sure you want to create this branch? 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. P.L. Evol. Extended Data Fig. Correspondence to 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. J. Virol. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins. Using these breakpoints, the longest putative non-recombining segment (nt1,88521,753) is 9.9kb long, and we call this region NRR2. the development of viral diversity. 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). (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. In the presence of time-dependent rate variation, a widely observed phenomenon for viruses43,44,52, slower prior rates appear more appropriate for sarbecoviruses that currently encompass a sampling time range of about 18years. Did Pangolin Trafficking Cause the Coronavirus Pandemic? 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. This long divergence period suggests there are unsampled virus lineages circulating in horseshoe bats that have zoonotic potential due to the ancestral position of the human-adapted contact residues in the SARS-CoV-2 RBD. Sequencing from Malayan pangolins collected during anti-smuggling operations in southern China detected coronavirus lineages related to SARS-CoV-2. However, on closer inspection, the relative divergences in the phylogenetic tree (Fig. 32, 268274 (2014). B 281, 20140732 (2014). 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 ). For weather, science, and COVID-19 . 90, 71847195 (2016). Removal of five sequences that appear to be recombinants and two small subregions of BFRA was necessary to ensure that there were no phylogenetic incongruence signals among or within the three BFRs. We thank all authors who have kindly deposited and shared genome data on GISAID. Although the human ACE2-compatible RBD was very likely to have been present in a bat sarbecovirus lineage that ultimately led to SARS-CoV-2, this RBD sequence has hitherto been found in only a few pangolin viruses. Coronavirus: Pangolins may have spread the disease to humans Anderson, K. G. nCoV-2019 codon usage and reservoir (not snakes v2). Stegeman, A. et al. USA 113, 30483053 (2016). Extended Data Fig. Pango lineage designation and assignment using SARS-CoV-2 - PubMed Article Gorbalenya, A. E. et al. Allen O'Brien on LinkedIn: #r #rstudio #rstats #pangolin #covid19 # 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. Biol. But some theories suggest that pangolins may be the source of the novel coronavirus. Stamatakis, A. RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. Nature 583, 286289 (2020). Lin, X. et al. DRAGEN COVID Lineage App This app aligns reads to a SARS-CoV-2 reference genome and reports coverage of targeted regions. & Li, X. Crossspecies transmission of the newly identified coronavirus 2019nCoV. Martin, D. P., Murrell, B., Golden, M., Khoosal, A. 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. 17, 15781579 (1999). PubMed Posada, D., Crandall, K. A. Microbiol. Evol. Green boxplots show the TMRCA estimate for the RaTG13/SARS-CoV-2 lineage and its most closely related pangolin lineage (Guangdong 2019). Pangolins: What are they and why are they linked to Covid-19? - Inverse Patino-Galindo, J. Genet. This boundary appears to be rarely crossed. You are using a browser version with limited support for CSS. Future trajectory of SARS-CoV-2: Constant spillover back and forth 36)gives a putative recombination-free alignment that we call non-recombinant alignment3 (NRA3) (see Methods). 5. 62,63), the GTR+ model and 100bootstrap replicateswas inferred for each BFR >500nt. 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. Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus. 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. Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor. Subsequently a bat sarbecovirusRaTG13, sampled from a Rhinolophus affinis horseshoe bat in 2013 in Yunnan Provincewas reported that clusters with SARS-CoV-2 in almost all genomic regions with approximately 96% genome sequence identity2. 31922087). 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. 206298/Z/17/Z. 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. Wong, A. C. P., Li, X., Lau, S. K. P. & Woo, P. C. Y. The origins we present in Fig. In December 2019, a cluster of pneumonia cases epidemiologically linked to an open-air live animal market in the city of Wuhan (Hubei Province), China1,2 led local health officials to issue an epidemiological alert to the Chinese Center for Disease Control and Prevention and the World Health Organizations (WHO) China Country Office. eLife 7, e31257 (2018). Bioinformatics 30, 13121313 (2014). stand-alone pangolin work flows or Illumina DRAGEN COVID Lineage App (v3.5.5) following the default parameters. Holmes, E. C. The Evolution and Emergence of RNA Viruses (Oxford Univ. A third approach attempted to minimize the number of regions removed while also minimizing signals of mosaicism and homoplasy. More evidence Pangolin not intermediary in transmission of SARS-CoV-2 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. Boxes show 95% HPD credible intervals. From this perspective, it may be useful to perform surveillance for more closely related viruses to SARS-CoV-2 along the gradient from Yunnan to Hubei. Discovery and genetic analysis of novel coronaviruses in least horseshoe bats in southwestern China. Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage responsible for the COVID-19 pandemic. Current sampling of pangolins does not implicate them as an intermediate host. 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. In our analyses of the sarbecovirus datasets, we incorporated the uncertainty of the sampling dates when exact dates were not available. 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. Forni, D., Cagliani, R., Clerici, M. & Sironi, M. Molecular evolution of human coronavirus genomes. 4 TMRCAs for SARS-CoV and SARS-CoV-2. Trova, S. et al. It allows a user to assign a SARS-CoV-2 genome sequence the most likely lineage (Pango lineage) to SARS-CoV-2 query sequences. To evaluate the performance procedure, we confirmed that the recombination masking resulted in (1) a markedly different outcome of the PHI test64, (2) removal of well-supported (bootstrap value >95%) incompatible splits in Neighbor-Net65 and (3) a near-complete reduction of mosaic signal as identified by 3SEQ. Holmes, E. C., Dudas, G., Rambaut, A. RegionB is 5,525nt long. 3). Sequence similarity. 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). 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. Xiao, K. et al. J. Gen. Virol. This statement informs us of the possibility that a virus has spilled over from a very rare and shy reptile-looking mammal . These datasets were subjected to the same recombination masking approach as NRA3 and were characterized by a strong temporal signal (Fig. Webster, R. G., Bean, W. J., Gorman, O. T., Chambers, T. M. & Kawaoka, Y. Evolution and ecology of influenza A viruses. A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist Provided by the Springer Nature SharedIt content-sharing initiative, Molecular and Cellular Biochemistry (2023), Nature Microbiology (Nat Microbiol) 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. Ji, W., Wang, W., Zhao, X., Zai, J. 2a. 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 ). Lemey, P., Minin, V. N., Bielejec, F., Pond, S. L. K. & Suchard, M. A. Using both prior distributions, this results in six highly similar posterior rate estimates for NRR1, NRR2 and NRA3, centred around 0.00055 substitutions per siteyr1. Nature 579, 270273 (2020). Accurate estimation of ages for deeper nodes would require adequate accommodation of time-dependent rate variation. 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). 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 TreeAnnotator to summarize posterior tree distributions and annotated the estimated values to a maximum clade credibility tree, which was visualized using FigTree. 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 . performed recombination and phylogenetic analysis and annotated virus names with geographical and sampling dates. 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. Don't blame pangolins, coronavirus family tree tracing could prove key Lie, P., Chen, W. & Chen, J.-P. He, B. et al. Extensive diversity of coronaviruses in bats from China. 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. PubMed Central A counting renaissance: combining stochastic mapping and empirical Bayes to quickly detect amino acid sites under positive selection. 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. In regionA, we removed subregion A1 (ntpositions 3,8724,716 within regionA) and subregion A4 (nt1,6422,113) because both showed PI signals with other subregions of regionA. a, Breakpoints identified by 3SEQ illustrated by percentage of sequences (out of 68) that support a particular breakpoint position. 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