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. He, B. et al. 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. 31922087). Early detection via genomics was not possible during Southeast Asias initial outbreaks of avian influenza H5N1 (1997 and 20032004) or the first SARS outbreak (20022003). Biol. 36, 17931803 (2019). 1c). J. Virol.
Frontiers | Novel Highly Divergent SARS-CoV-2 Lineage With the Spike CNN . with an alignment on which an initial recombination analysis was done. Lancet 395, 565574 (2020). Using a third consensus-based approach for identifying recombinant regions in individual sequenceswith six different recombination detection methods in RDP5 (ref. 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. 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 ). Sign up for the Nature Briefing newsletter what matters in science, free to your inbox daily. A tag already exists with the provided branch name. Grey tips correspond to bat viruses, green to pangolin, blue to SARS-CoV and red to SARS-CoV-2. Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage responsible for the COVID-19 pandemic. 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. SARS-CoV-2 is an appropriate name for the new coronavirus. Nat Microbiol 5, 14081417 (2020). 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. Stamatakis, A. RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models. 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. Virology 507, 110 (2017). Lie, P., Chen, W. & Chen, J.-P. In light of these time-dependent evolutionary rate dynamics, a slower rate is appropriate for calibration of the sarbecovirus evolutionary history. Genetics 176, 10351047 (2007). performed recombination analysis for non-recombining regions1 and 2, breakpoint analysis and phylogenetic inference on recombinant segments. R. Soc. Liu, P. et al. D.L.R. 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). Webster, R. G., Bean, W. J., Gorman, O. T., Chambers, T. M. & Kawaoka, Y. Evolution and ecology of influenza A viruses. It compares the new genome against the large, diverse population of sequenced strains using a Aside from RaTG13, Pangolin-CoV is the most closely related CoV to SARS-CoV-2. 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. Nature 503, 535538 (2013). Now, the two researchers used genomic sequencing to compare the DNA of the new coronavirus in humans with that in animals and found a 99% match with pangolins. 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. 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). 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. Five example sequences with incongruent phylogenetic positions in the two trees are indicated by dashed lines. 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. Nature 579, 265269 (2020). These shy, quirky but cute mammals are one of the most heavily trafficked yet least understood animals in the world. 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). a, Breakpoints identified by 3SEQ illustrated by percentage of sequences (out of 68) that support a particular breakpoint position. and T.A.C. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Boni, M. F., de Jong, M. D., van Doorn, H. R. & Holmes, E. C. Guidelines for identifying homologous recombination events in influenza A virus. Due to the absence of temporal signal in the sarbecovirus datasets, we used informative prior distributions on the evolutionary rate to estimate divergence dates. To avoid artefacts due to recombination, we focused on NRR1 and NRR2 and the recombination-masked alignment NRA3 to infer time-measured evolutionary histories. We thank all authors who have kindly deposited and shared genome data on GISAID. 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). 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 .
Phylogenetic classification of the whole-genome sequences of SARS-CoV-2 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. Because these subclades had different phylogenetic relationships in regionD (Supplementary Fig. 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. 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. Gray inset shows majority rule consensus trees with mean posterior branch lengths for the two regions, with posterior probabilities on the key nodes showing the relationships among SARS-CoV-2, RaTG13, and Pangolin 2019. M.F.B. Extended Data Fig. 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. Extensive diversity of coronaviruses in bats from China. Google Scholar. Hu, B. et al. Biol. Zhang, Y.-Z. Evol. Extended Data Fig. Note that six of these sequences fall under the terms of use of the GISAID platform. 4, vey016 (2018). Article If stopping an outbreak in its early stages is not possibleas was the case for the COVID-19 epidemic in Hubeiidentification of origins and point sources is nevertheless important for containment purposes in other provinces and prevention of future outbreaks. 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. 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). Anderson, K. G., Rambaut, A., Lipkin, W. I., Holmes, E. C. & Garry, R. F. The proximal origin of SARS-CoV-2. 4), but also by markedly different evolutionary rates. 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. 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. Epidemiology, genetic recombination, and pathogenesis of coronaviruses. 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. 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. Lancet 383, 541548 (2013). pango-designation Public Repository for suggesting new lineages that should be added to the current scheme Python 968 73 pangolin Public Software package for assigning SARS-CoV-2 genome sequences to global lineages. J. Virol. Methods Ecol. Viral metagenomics revealed Sendai virus and coronavirus infection of Malayan pangolins (Manis javanica). 62,63), the GTR+ model and 100bootstrap replicateswas inferred for each BFR >500nt. This leaves the insertion of polybasic. 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 . The origins we present in Fig. Nature 579, 270273 (2020). Sequences were aligned by MAFTT58 v.7.310, with a final alignment length of 30,927, and used in the analyses below. 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. Accurate estimation of ages for deeper nodes would require adequate accommodation of time-dependent rate variation. In case of DRAGEN COVID Lineage tool, the minimum accepted alignment score was set to 22 and results with scores <22 were discarded. 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. 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 . T.L. Even before the COVID-19 pandemic, pangolins have been making headlines. Published. Add entries for pangolin-data/-assignment 1.18.1.1 (, Really add a document on testing strategy. Curr. 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.
Current Overview on Disease and Health Research Vol. 6 90, 71847195 (2016). It is available as a command line tool and a web application. PubMed Central J. Virol.
Coronavirus origins: genome analysis suggests two viruses may have combined 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. Biol. Several of the recombinant sequences in these trees show that recombination events do occur across geographically divergent clades. Software package for assigning SARS-CoV-2 genome sequences to global lineages. 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).