J. Virol. Unlike other viruses that have emerged in the past two decades, coronaviruses are highly recombinogenic14,15,16. Bayesian phylogenetic and phylodynamic data integration using BEAST 1.10. 6, eabb9153 (2020). performed recombination and phylogenetic analysis and annotated virus names with geographical and sampling dates. 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). 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. Identification of diverse alphacoronaviruses and genomic characterization of a novel severe acute respiratory syndrome-like coronavirus from bats in China. Patino-Galindo, J. Share . Use the Previous and Next buttons to navigate the slides or the slide controller buttons at the end to navigate through each slide. 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. 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. Stamatakis, A. RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models. 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. GARD identified eight breakpoints that were also within 50nt of those identified by 3SEQ. 88, 70707082 (2014). 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. 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). COVID-19: Time to exonerate the pangolin from the transmission of SARS Lancet 395, 949950 (2020). Google Scholar. Nature 503, 535538 (2013). CAS Coronavirus Software Tools - Illumina, Inc. & Li, X. Crossspecies transmission of the newly identified coronavirus 2019nCoV. 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). 2). Duchene, S. et al. Slider with three articles shown per slide. 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 CAS Boni, M. F., Zhou, Y., Taubenberger, J. K. & Holmes, E. C. Homologous recombination is very rare or absent in human influenza A virus. More evidence Pangolin not intermediary in transmission of SARS-CoV-2 The idea is that pangolins carrying the virus, SARS-CoV-2, came into contact with humans. 3 Priors and posteriors for evolutionary rate of SARS-CoV-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. Discovery and genetic analysis of novel coronaviruses in least horseshoe bats in southwestern China. 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. All sequence data analysed in this manuscript are available at https://github.com/plemey/SARSCoV2origins. Another similarity between SARS-CoV and SARS-CoV-2 is their divergence time (4070years ago) from currently known extant bat virus lineages (Fig. Boxes show 95% HPD credible intervals. Holmes, E. C. The Evolution and Emergence of RNA Viruses (Oxford Univ. Med. Gorbalenya, A. E. et al. In the variable-loop region, RaTG13 diverges considerably with the TMRCA, now outside that of SARS-CoV-2 and the Pangolin Guangdong 2019 ancestor, suggesting that RaTG13 has acquired this region from a more divergent and undetected bat lineage. Anderson, K. G., Rambaut, A., Lipkin, W. I., Holmes, E. C. & Garry, R. F. The proximal origin of SARS-CoV-2. Nat. 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. 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. A new coronavirus associated with human respiratory disease in China. Split diversity in constrained conservation prioritization using integer linear programming. The web application was developed by the Centre for Genomic Pathogen Surveillance. The histogram allows for the identification of non-recombining regions (NRRs) by revealing regions with no breakpoints. Python 379 102 pangoLEARN Public Store of the trained model for pangolin to access. 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. However, for several reasons, nucleotide sequences may be generated that cover only the spike gene of SARS-CoV-2. B., Weaver, S. & Sergei, L. Evidence of significant natural selection in the evolution of SARS-CoV-2 in bats, not humans. Kosakovsky Pond, S. L., Posada, D., Gravenor, M. B., Woelk, C. H. & Frost, S. D. W. Automated phylogenetic detection of recombination using a genetic algorithm. 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. Posterior distributions were approximated through Markov chain Monte Carlo sampling, which were run sufficiently long to ensure effective sampling sizes >100. PI signals were identified (with bootstrap support >80%) for seven of these eight breakpoints: positions 1,684, 3,046, 9,237, 11,885, 21,753, 22,773 and 24,628. 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 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). There is a 90% DNA match between SARS CoV 2 and a coronavirus in pangolins. Combining regions A, B and C and removing the five named sequences gives us putative NRR1, as an alignment of 63sequences. It compares the new genome against the large, diverse population of sequenced strains using a Humans' selfish, speciesist treatment of these animals could be the very reason why the novel coronavirus exists. This boundary appears to be rarely crossed. Rambaut, A., Lam, T. T., Carvalho, L. M. & Pybus, O. G. Exploring the temporal structure of heterochronous sequences using TempEst (formerly Path-O-Gen). 92, 433440 (2020). 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. Viruses 11, 174 (2019). 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. Coronavirus: Pangolins found to carry related strains - BBC News Using a third consensus-based approach for identifying recombinant regions in individual sequenceswith six different recombination detection methods in RDP5 (ref. performed recombination analysis for non-recombining regions1 and 2, breakpoint analysis and phylogenetic inference on recombinant segments. Microbiol. Bioinformatics 22, 26882690 (2006). Based on the identified breakpoints in each genome, only the major non-recombinant region is kept in each genome while other regions are masked. SARS-CoV-2 Variant Classifications and Definitions Evol. Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus. By 2009, however, rapid genomic analysis had become a routine component of outbreak response. 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. 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. Coronavirus origins: genome analysis suggests two viruses may have combined 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. Article PubMed Central Don't blame pangolins, coronavirus family tree tracing could prove key Phylogenetic supertree reveals detailed evolution of SARS-CoV-2, Origin and cross-species transmission of bat coronaviruses in China, Emerging SARS-CoV-2 variants follow a historical pattern recorded in outgroups infecting non-human hosts, Inferring the ecological niche of bat viruses closely related to SARS-CoV-2 using phylogeographic analyses of Rhinolophus species, Genomic recombination events may reveal the evolution of coronavirus and the origin of SARS-CoV-2, A Bayesian approach to infer recombination patterns in coronaviruses, Metagenomic identification of a new sarbecovirus from horseshoe bats in Europe, A comparative recombination analysis of human coronaviruses and implications for the SARS-CoV-2 pandemic, Pandemic-scale phylogenomics reveals the SARS-CoV-2 recombination landscape, https://github.com/plemey/SARSCoV2origins, https://doi.org/10.1101/2020.04.20.052019, https://doi.org/10.1101/2020.02.10.942748, https://doi.org/10.1101/2020.05.28.122366, http://virological.org/t/ncov-2019-codon-usage-and-reservoir-not-snakes-v2/339, http://virological.org/t/ncovs-relationship-to-bat-coronaviruses-recombination-signals-no-snakes-no-evidence-the-2019-ncov-lineage-is-recombinant/331. . Virological.org http://virological.org/t/ncov-2019-codon-usage-and-reservoir-not-snakes-v2/339 (2020). Intraspecies diversity of SARS-like coronaviruses in Rhinolophus sinicus and its implications for the origin of SARS coronaviruses in humans. 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. 87, 62706282 (2013). 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. To obtain We demonstrate that the sarbecoviruses circulating in horseshoe bats have complex recombination histories as reported by others15,20,21,22,23,24,25,26. Eden, J.-S., Tanaka, M. M., Boni, M. F., Rawlinson, W. D. & White, P. A. Recombination within the pandemic norovirus GII.4 lineage. & Boni, M. F. Improved algorithmic complexity for the 3SEQ recombination detection algorithm. 110. Biol. RegionB showed no PI signals within the region, except one including sequence SC2018 (Sichuan), and thus this sequence was also removed from the set. Graham, R. L. & Baric, R. S. Recombination, reservoirs, and the modular spike: mechanisms of coronavirus cross-species transmission. 725422-ReservoirDOCS). 35, 247251 (2018). 04:20. Holmes, E. C., Dudas, G., Rambaut, A. . A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. COVID-19: A Catastrophe or Opportunity for Pangolin Conservation? - Nature These rate priors are subsequently used in the Bayesian inference of posterior rates for NRR1, NRR2, and NRA3 as indicated by the solid arrows. The origins we present in Fig. Genetics 172, 26652681 (2006). 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 . For the HCoV-OC43, MERS-CoV and SARS datasets we specified flexible skygrid coalescent tree priors. The rate of genome generation is unprecedented, yet there is currently no coherent nor accepted scheme for naming the expanding . A third approach attempted to minimize the number of regions removed while also minimizing signals of mosaicism and homoplasy. Wu, F. et al. Frontiers | Novel Highly Divergent SARS-CoV-2 Lineage With the Spike Hon, C. et al. Conducting analogous analyses of codon usage bias as Ji et al. Mol. By mid-January 2020, the virus was spreading widely within Hubei province and by early March SARS-CoV-2 was declared a pandemic8.
