Sliding window analysis of changes in the patterns of sequence similarity between human SARS-CoV-2, and pangolin and bat coronaviruses as described further in Fig. Stamatakis, A. RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Anderson, K. G., Rambaut, A., Lipkin, W. I., Holmes, E. C. & Garry, R. F. The proximal origin of SARS-CoV-2. Lin, X. et al. 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. However, inconsistency in the nomenclature limits uniformity in its epidemiological understanding. Wang, L. et al. In this study, we report the case of a child with severe combined immu presenting a prolonged severe acute respiratory syndrome coronavirus 2 infection. BEAST inferences made use of the BEAGLE v.3 library68 for efficient likelihood computations. This leaves the insertion of polybasic. ISSN 2058-5276 (online). 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. 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. The presence of SARS-CoV-2-related viruses in Malayan pangolins, in silico analysis of the ACE2 receptor polymorphism and sequence similarities between the Receptor Binding Domain (RBD) of the spike proteins of pangolin and human Sarbecoviruses led to the proposal of pangolin as intermediary. 874850). 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 Yres, D. L. et al. 382, 11991207 (2020). J. Virol. Biol. USA 113, 30483053 (2016). Microbiol. 26, 450452 (2020). The research leading to these results received funding (to A.R. Epidemiology, genetic recombination, and pathogenesis of coronaviruses. 4), but also by markedly different evolutionary rates. Using these breakpoints, the longest putative non-recombining segment (nt1,88521,753) is 9.9kb long, and we call this region NRR2. 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. Posterior distributions were approximated through Markov chain Monte Carlo sampling, which were run sufficiently long to ensure effective sampling sizes >100. 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. We compiled a set of 69SARS-CoV genomes including 58 sampled from humans and 11 sampled from civets and raccoon dogs. c, Maximum likelihood phylogenetic trees rooted on a 2007 virus sampled in Kenya (BtKy72; root truncated from images), shown for five BFRs of the sarbecovirus alignment. 35, 247251 (2018). Note that breakpoints can be shared between sequences if they are descendants of the same recombination events. 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. Internet Explorer). Liu, P. et al. 21, 255265 (2004). Extended Data Fig. A second breakpoint-conservative approach was conservative with respect to breakpoint identification, but this means that it is accepting of false-negative outcomes in breakpoint inference, resulting in less certainty that a putative NRR truly contains no breakpoints. Lancet 383, 541548 (2013). 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. RegionsB and C span nt3,6259,150 and 9,26111,795, respectively. Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins. In Extended Data Fig. We thank A. Chan and A. Irving for helpful comments on the manuscript. Virological.org http://virological.org/t/ncov-2019-codon-usage-and-reservoir-not-snakes-v2/339 (2020). 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. 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. Rev. It is RaTG13 that is more divergent in the variable-loop region (Extended Data Fig. P.L. Divergence time estimates based on the three regions/alignments where the effects of recombination have been removed. Because these subclades had different phylogenetic relationships in regionD (Supplementary 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 To estimate non-synonymous over synonymous rate ratios for the concatenated coding genes, we used the empirical Bayes Renaissance countingprocedure67. Accurate estimation of ages for deeper nodes would require adequate accommodation of time-dependent rate variation. b, Similarity plot between SARS-CoV-2 and several selected sequences including RaTG13 (black), SARS-CoV (pink) and two pangolin sequences (orange). However, on closer inspection, the relative divergences in the phylogenetic tree (Fig. 1, vev016 (2015). Zhou et al.2 concluded from the genetic proximity of SARS-CoV-2 to RaTG13 that a bat origin for the current COVID-19 outbreak is probable. Split diversity in constrained conservation prioritization using integer linear programming. Humans' selfish, speciesist treatment of these animals could be the very reason why the novel coronavirus exists. 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. Specifically, we used a combination of six methods implemented in v.5.5 of RDP5 (ref. A hypothesis of snakes as intermediate hosts of SARS-CoV-2 was posited during the early epidemic phase54, but we found no evidence of this55,56; see Extended Data Fig. 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. By 2009, however, rapid genomic analysis had become a routine component of outbreak response. Eight other BFRs <500nt were identified, and the regions were named BFRAJ in order of length. 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. A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. 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 . Alternatively, combining 3SEQ-inferred breakpoints, GARD-inferred breakpoints and the necessity of PI signals for inferring recombination, we can use the 9.9-kb region spanning nucleotides 11,88521,753 (NRR2) as a putative non-recombining region; this approach is breakpoint-conservative because it is conservative in identifying breakpoints but not conservative in identifying non-recombining regions. 1 Phylogenetic relationships in the C-terminal domain (CTD). Katoh, K., Asimenos, G. & Toh, H. in Bioinformatics for DNA Sequence Analysis (ed. 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. Robertson, D. nCoVs relationship to bat coronaviruses & recombination signals (no snakes) no evidence the 2019-nCoV lineage is recombinant. Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor. In our second stage, we wanted to construct non-recombinant regions where our approach to breakpoint identification was as conservative as possible. It allows a user to assign a SARS-CoV-2 genome sequence the most likely lineage (Pango lineage) to SARS-CoV-2 query sequences. 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. 3). The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. 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. . Emerg. SARS-CoV-2 and RaTG13 are also exceptions because they were sampled from Hubei and Yunnan, respectively. In light of these time-dependent evolutionary rate dynamics, a slower rate is appropriate for calibration of the sarbecovirus evolutionary history. But some theories suggest that pangolins may be the source of the novel coronavirus. Extended Data Fig. 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). 4). As of December 2, 2021, SJdRP, a medium-sized city in the Northwest region of So Paulo state, Brazil (Fig. RegionC showed no PI signals within it. Lam, T. T. et al. Phylogenetic Assignment of Named Global Outbreak LINeages, The pangolin web app is maintained by the Centre for Genomic Pathogen Surveillance. The inset represents divergence time estimates based on NRR1, NRR2 and NRA3. Extended Data Fig. The relatively fast evolutionary rate means that it is most appropriate to estimate shallow nodes in the sarbecovirus evolutionary history. Except for specifying that sequences are linear, all settings were kept to their defaults. 2). SARS-CoV-2 genetic lineages in the United States are routinely monitored through epidemiological investigations, virus genetic sequence-based surveillance, and laboratory studies. Despite the SARS-CoV-2 lineages acquisition of residues in its Spike (S) proteins receptor-binding domain (RBD) permitting the use of human ACE2 (ref. Li, Q. et al. Press, 2009). When the first genome sequence of SARS-CoV-2, Wuhan-Hu-1, was released on 10January 2020 (GMT) on Virological.org by a consortium led by Zhang6, it enabled immediate analyses of its ancestry. =0.00025. We demonstrate that the sarbecoviruses circulating in horseshoe bats have complex recombination histories as reported by others15,20,21,22,23,24,25,26. 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. The command line tool is open source software available under the GNU General Public License v3.0. Eden, J.-S., Tanaka, M. M., Boni, M. F., Rawlinson, W. D. & White, P. A. Recombination within the pandemic norovirus GII.4 lineage. While there is evidence of positive selection in the sarbecovirus lineage leading to RaTG13/SARS-CoV-2 (ref. A., Filip, I., AlQuraishi, M. & Rabadan, R. Recombination and lineage-specific mutations led to the emergence of SARS-CoV-2. GitHub - cov-lineages/pangolin: Software package for assigning SARS-CoV-2 genome sequences to global lineages. Virus Evol. Regions AC were further examined for mosaic signals by 3SEQ, and all showed signs of mosaicism. After removal of A1 and A4, we named the new region A. 3). 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. 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. Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus. Microbes Infect. Preprint at https://doi.org/10.1101/2020.04.20.052019 (2020). The origins we present in Fig. According to GISAID . Use the Previous and Next buttons to navigate the slides or the slide controller buttons at the end to navigate through each slide. He, B. et al. 95% credible interval bars are shown for all internal node ages. Another similarity between SARS-CoV and SARS-CoV-2 is their divergence time (4070years ago) from currently known extant bat virus lineages (Fig. PubMed matics program called Pangolin was developed. 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. Nat. We showed that severe acute respiratory syndrome coronavirus 2 is probably a novel recombinant virus. CAS J. Med. J. Virol. Wang, H., Pipes, L. & Nielsen, R. Synonymous mutations and the molecular evolution of SARS-Cov-2 origins. PLoS ONE 5, e10434 (2010). Consistent with this, we estimate a concomitantly decreasing non-synonymous-to-synonymous substitution rate ratio over longer evolutionary timescales: 1.41 (1.20,1.68), 0.35 (0.30,0.41) and 0.133 (0.129,0.136) for SARS, MERS-CoV and HCoV-OC43, respectively. 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 . Press, H.) 3964 (Springer, 2009). Annu Rev. Biazzo et al. with an alignment on which an initial recombination analysis was done. Biol. The virus then. 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). Abstract. PLoS Pathog. Gorbalenya, A. E. et al. PubMed Google Scholar. 4 TMRCAs for SARS-CoV and SARS-CoV-2. Get the most important science stories of the day, free in your inbox. 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. Hon, C. et al. Boxes show 95% HPD credible intervals. is funded by The National Natural Science Foundation of China Excellent Young Scientists Fund (Hong Kong and Macau; no. Google Scholar. stand-alone pangolin work flows or Illumina DRAGEN COVID Lineage App (v3.5.5) following the default parameters. Evol. RegionB showed no PI signals within the region, except one including sequence SC2018 (Sichuan), and thus this sequence was also removed from the set. Mol. 4. 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. & Bedford, T. MERS-CoV spillover at the camelhuman interface. Transparent bands of interquartile range width and with the same colours are superimposed to highlight the overlap between estimates. 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 . BEAGLE 3: improved performance, scaling, and usability for a high-performance computing library for statistical phylogenetics. Lam, H. M., Ratmann, O. Emergence of SARS-CoV-2 through recombination and strong purifying selection. 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. 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. CAS 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. 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 (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). 5. The S1 protein of Pangolin-CoV is much more closely related to SARS-CoV-2 than to RaTG13. 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)). 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. Li, X. et al. The 2009 influenza pandemic and subsequent outbreaks of MERS-CoV (2012), H7N9 avian influenza (2013), Ebola virus (2014) and Zika virus (2015) were met with rapid sequencing and genomic characterization. Bioinformatics 28, 32483256 (2012). Even before the COVID-19 pandemic, pangolins have been making headlines. 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. To avoid artefacts due to recombination, we focused on NRR1 and NRR2 and the recombination-masked alignment NRA3 to infer time-measured evolutionary histories. Effect of closure of live poultry markets on poultry-to-person transmission of avian influenza A H7N9 virus: an ecological study. 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. Visual exploration using TempEst39 indicates that there is no evidence for temporal signal in these datasets (Extended Data Fig. 4), that region and shorter BFRs were not included in combined putative non-recombinant regions. B.W.P. 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). and D.L.R. Trends Microbiol. PANGOLIN lineage database (15, 16) was used to analyze the frequency of lineages among countries. Using a third consensus-based approach for identifying recombinant regions in individual sequenceswith six different recombination detection methods in RDP5 (ref. Identification of diverse alphacoronaviruses and genomic characterization of a novel severe acute respiratory syndrome-like coronavirus from bats in China. Cell 181, 223227 (2020). Grey tips correspond to bat viruses, green to pangolin, blue to SARS-CoV and red to SARS-CoV-2. Ge, X. et al. 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 Aside from RaTG13, Pangolin-CoV is the most closely related CoV to SARS-CoV-2. The consistency of the posterior rates for the different prior means also implies that the data do contribute to the evolutionary rate estimate, despite the fact that a temporal signal was visually not apparent (Extended Data Fig. Boni, M. F., Posada, D. & Feldman, M. W. An exact nonparametric method for inferring mosaic structure in sequence triplets. # 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 Are you sure you want to create this branch? Conservatively, we combined the three BFRs >2kb identified above into non-recombining region1 (NRR1). Nature 579, 265269 (2020). 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. Coronavirus: Pangolins found to carry related strains. 36, 17931803 (2019). Evol. 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. https://doi.org/10.1093/molbev/msaa163 (2020). 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. Sequences are colour-coded by province according to the map. =0.00075 and one with a mean of 0.00024 and s.d. 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. 36) (RDP, GENECONV, MaxChi, Bootscan, SisScan and 3SEQ) and considered recombination signals detected by more than two methods for breakpoint identification. Originally, PANGOLIN used a maximum-likelihood-based assignment algorithm to assign query SARS-CoV-2 the most likely lineage sequence. Genetics 176, 10351047 (2007). Smuggled pangolins were carrying viruses closely related to the one sweeping the world, say scientists. 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. 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. Martin, D. P., Murrell, B., Golden, M., Khoosal, A. 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. performed Srecombination analysis. A tag already exists with the provided branch name. Proc. Evol. Complete genome sequence data were downloaded from GenBank and ViPR; accession numbers of all 68sequences are available in Supplementary Table 4. 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. 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. 1, vev003 (2015). obtained the genome sequences of 10 SARS-CoV-2 virus strains through nanopore sequencing of nasopharyngeal swabs in Malta and analyzed the assembled genome with pangolin software, and the results showed that these virus strains were assigned to B.1 lineage, indicating that SARS-CoV-2 was widely spread in Europe (Biazzo et al., 2021). B 281, 20140732 (2014). Mol. Developed by the Centre for Genomic Pathogen Surveillance. 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 . CNN . Pangolin was developed to implement the dynamic nomenclature of SARS-CoV-2 lineages, known as the Pango nomenclature. Biol. Further information on research design is available in the Nature Research Reporting Summary linked to this article. 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. 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). 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. 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. Mol. 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. CAS In the meantime, to ensure continued support, we are displaying the site without styles 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. Duchene, S., Holmes, E. C. & Ho, S. Y. W. Analyses of evolutionary dynamics in viruses are hindered by a time-dependent bias in rate estimates. PubMed is funded by the MRC (no. Google Scholar. Holmes, E. C. The Evolution and Emergence of RNA Viruses (Oxford Univ. To obtain Provided by the Springer Nature SharedIt content-sharing initiative, Molecular and Cellular Biochemistry (2023), Nature Microbiology (Nat Microbiol)