pangolin lineage covid pangolin lineage covid

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. Boni, M.F., Lemey, P., Jiang, X. et al. 92, 433440 (2020). 1) and thus likely to be the product of recombination, acquiring a divergent variable loop from a hitherto unsampled bat sarbecovirus28. Unfortunately, a response that would achieve containment was not possible. Extensive diversity of coronaviruses in bats from China. Lam, T. T. et al. 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. Posterior means (horizontal bars) of patristic distances between SARS-CoV-2 and its closest bat and pangolin sequences, for the spike proteins variable loop region and CTD region excluding the variable loop. 2). Preprint at https://doi.org/10.1101/2020.04.20.052019 (2020). Share . 190, 20882095 (2004). Biol. The construction of NRR1 is the most conservative as it is least likely to contain any remaining recombination signals. MC_UU_1201412). 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. Python 379 102 pangoLEARN Public Store of the trained model for pangolin to access. 68, 10521061 (2019). https://doi.org/10.1038/s41564-020-0771-4, DOI: https://doi.org/10.1038/s41564-020-0771-4. Researchers in the UK had just set the scientific world . Download a free copy. Natl Acad. the development of viral diversity. SARS-CoV-2 genetic lineages in the United States are routinely monitored through epidemiological investigations, virus genetic sequence-based surveillance, and laboratory studies. Hu, B. et al. RegionB showed no PI signals within the region, except one including sequence SC2018 (Sichuan), and thus this sequence was also removed from the set. 82, 18191826 (2008). Extended Data Fig. 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. 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. 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 And this genotype pattern led to creating a new Pangolin lineage named B.1.640.2, a phylogenetic sister group to the old B.1.640 lineage renamed B.1.640.1. 1 Phylogenetic relationships in the C-terminal domain (CTD). 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. Virological.org http://virological.org/t/ncov-2019-codon-usage-and-reservoir-not-snakes-v2/339 (2020). Emergence of SARS-CoV-2 through recombination and strong purifying selection. 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. Biol. GitHub - cov-lineages/pangolin: Software package for assigning SARS-CoV-2 genome sequences to global lineages. 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. Stamatakis, A. RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models. M.F.B. Further information on research design is available in the Nature Research Reporting Summary linked to this article. The fact that they are geographically relatively distant is in agreement with their somewhat distant TMRCA, because the spatial structure suggests that migration between their locations may be uncommon. Root-to-tip divergence as a function of sampling time for non-recombinant regions NRR1 and NRR2 and recombination-masked alignment set NRA3. Holmes, E. C. The Evolution and Emergence of RNA Viruses (Oxford Univ. matics program called Pangolin was developed. Wu, F. et al. Posada, D., Crandall, K. A. J. Med. =0.00025. 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). 1, vev016 (2015). PANGOLIN lineage database (15, 16) was used to analyze the frequency of lineages among countries. Google Scholar. Region A has been shortened to A (5,017nt) based on potential recombination signals within the region. # 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 Google Scholar. Nature 583, 286289 (2020). Article is funded by The National Natural Science Foundation of China Excellent Young Scientists Fund (Hong Kong and Macau; no. Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage responsible for the COVID-19 pandemic. Furthermore, the other key feature thought to be instrumental in the ability of SARS-CoV-2 to infect humansa polybasic cleavage site insertion in the Sproteinhas not yet been seen in another close bat relative of the SARS-CoV-2 virus. A., Filip, I., AlQuraishi, M. & Rabadan, R. Recombination and lineage-specific mutations led to the emergence of SARS-CoV-2. 4), but also by markedly different evolutionary rates. [12] T.L. 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. The time-calibrated phylogeny represents a maximum clade credibility tree inferred for NRR1. Holmes, E. C., Rambaut, A. Regions AC were further examined for mosaic signals by 3SEQ, and all showed signs of mosaicism. We used TreeAnnotator to summarize posterior tree distributions and annotated the estimated values to a maximum clade credibility tree, which was visualized using FigTree. Accurate estimation of ages for deeper nodes would require adequate accommodation of time-dependent rate variation. A tag already exists with the provided branch name. is funded by the MRC (no. Sci. Google Scholar. You are using a browser version with limited support for CSS. We compare both MERS-CoV- and HCoV-OC43-centred prior distributions (Extended Data Fig. Nature 503, 535538 (2013). Correspondence to 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. and JavaScript. Add entries for pangolin-data/-assignment 1.18.1.1 (, Really add a document on testing strategy. & Li, X. Crossspecies transmission of the newly identified coronavirus 2019nCoV. The Artic Network receives funding from the Wellcome Trust through project no. Nat. Several of the recombinant sequences in these trees show that recombination events do occur across geographically divergent clades. 1c). Divergence dates between SARS-CoV-2 and the bat sarbecovirus reservoir were estimated as 1948 (95% highest posterior density (HPD): 18791999), 1969 (95% HPD: 19302000) and 1982 (95% HPD: 19482009), indicating that the lineage giving rise to SARS-CoV-2 has been circulating unnoticed in bats for decades. Proc. Its origin and direct ancestral viruses have not been . Below, we report divergence time estimates based on the HCoV-OC43-centred rate prior for NRR1, NRR2 and NRA3 and summarize corresponding estimates for the MERS-CoV-centred rate priors in Extended Data Fig. After removal of A1 and A4, we named the new region A. Med. 3). 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. Wan, Y., Shang, J., Graham, R., Baric, R. & Li, F. Receptor recognition by the novel Coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus. performed recombination and phylogenetic analysis and annotated virus names with geographical and sampling dates. 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. 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. 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 . 35, 247251 (2018). 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. Xiao, K. et al. Relevant bootstrap values are shown on branches, and grey-shaded regions show sequences exhibiting phylogenetic incongruence along the genome. & Andersen, K. G. Pandemics: spend on surveillance, not prediction. Collectively our analyses point to bats being the primary reservoir for the SARS-CoV-2 lineage. SARS-CoV-2 is an appropriate name for the new coronavirus. 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. 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 . A pneumonia outbreak associated with a new coronavirus of probable bat origin. 21, 255265 (2004). =0.00075 and one with a mean of 0.00024 and s.d. Unlike other viruses that have emerged in the past two decades, coronaviruses are highly recombinogenic14,15,16. We thank T. Bedford for providing M.F.B. 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. 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 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 . 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. In March, when covid cases began spiking around India, Bani Jolly went hunting for answers in the virus's genetic code. T.T.-Y.L. Su, S. et al. CAS 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. These differences reflect the fact that rate estimates can vary considerably with the timescale of measurement, a frequently observed phenomenon in viruses known as time-dependent evolutionary rates41,43,44. Concatenated region ABC is NRR1. Decimal years are shown on the x axis for the 1.2 years of SARS sampling in c. d, Mean evolutionary rate estimates plotted against sampling time range for the same three datasets (represented by the same colour as the data points in their respective RtT divergence plots), as well as for the comparable NRA3 using the two different priors for the rate in the Bayesian inference (red points). Liu, P. 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. Extended Data Fig. Adv. Lin, X. et al. In this approach, we considered a breakpoint as supported only if it had three types of statistical support: from (1) mosaic signals identified by 3SEQ, (2) PI signals identified by building trees around 3SEQs breakpoints and (3) the GARD algorithm35, which identifies breakpoints by identifying PI signals across proposed breakpoints. Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus. 1. 16, e1008421 (2020). Because 3SEQ identified ten BFRs >500nt, we used GARDs (v.2.5.0) inference on 10, 11 and 12 breakpoints. Time-measured phylogenetic reconstruction was performed using a Bayesian approach implemented in BEAST42 v.1.10.4. It is available as a command line tool and a web application. 5). Two exceptions can be seen in the relatively close relationship of Hong Kong viruses to those from Zhejiang Province (with two of the latter, CoVZC45 and CoVZXC21, identified as recombinants) and a recombinant virus from Sichuan for which part of the genome (regionB of SC2018 in Fig. Note that breakpoints can be shared between sequences if they are descendants of the same recombination events. Methods Ecol. PLoS Pathog. A new coronavirus associated with human respiratory disease in China. 17, 15781579 (1999). Global epidemiology of bat coronaviruses. Smuggled pangolins were carrying viruses closely related to the one sweeping the world, say scientists. Grey tips correspond to bat viruses, green to pangolin, blue to SARS-CoV and red to SARS-CoV-2. Sequences are colour-coded by province according to the map. Boni, M. F., de Jong, M. D., van Doorn, H. R. & Holmes, E. C. Guidelines for identifying homologous recombination events in influenza A virus. SARS-like WIV1-CoV poised for human emergence. Indeed, the rates reported by these studies are in line with the short-term SARS rates that we estimate (Fig. Menachery, V. D. et al. 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 . 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. Sarbecovirus, HCoV-OC43 and SARS-CoV data were assembled from GenBank to be as complete as possible, with sampling year as an inclusion criterion. & Holmes, E. C. Recombination in evolutionary genomics. Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins. 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 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). Hon, C. et al. 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). This leaves the insertion of polybasic. Phylogenetic trees and exact breakpoints for all ten BFRs are shown in Supplementary Figs. However, for several reasons, nucleotide sequences may be generated that cover only the spike gene of SARS-CoV-2. Chernomor, O. et al. Trends Microbiol. 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. This new approach classifies the newly sequenced genome against all the diverse lineages present instead of a representative select sequences. Even before the COVID-19 pandemic, pangolins have been making headlines. But some theories suggest that pangolins may be the source of the novel coronavirus. 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. 88, 70707082 (2014). Transparent bands of interquartile range width and with the same colours are superimposed to highlight the overlap between estimates. To estimate non-synonymous over synonymous rate ratios for the concatenated coding genes, we used the empirical Bayes Renaissance countingprocedure67. The presence in pangolins of an RBD very similar to that of SARS-CoV-2 means that we can infer this was also probably in the virus that jumped to humans. For the HCoV-OC43, MERS-CoV and SARS datasets we specified flexible skygrid coalescent tree priors. Virus Evol. D.L.R. (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. 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. Published. BFRs were concatenated if no phylogenetic incongruence signal could be identified between them. 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. Patino-Galindo, J. 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. Originally, PANGOLIN used a maximum-likelihood-based assignment algorithm to assign query SARS-CoV-2 the most likely lineage sequence. Microbes Infect. 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. If the latter still identified non-negligible recombination signal, we removed additional genomes that were identified as major contributors to the remaining signal. 56, 152179 (1992). 2). 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. 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 . Because there is no single accepted method of inferring breakpoints and identifying clean subregions with high certainty, we implemented several approaches to identifying three classic statistical signals of recombination: mosaicism, phylogenetic incongruence and excessive homoplasy51. Robertson, D. nCoVs relationship to bat coronaviruses & recombination signals (no snakes) no evidence the 2019-nCoV lineage is recombinant. Wong, A. C. P., Li, X., Lau, S. K. P. & Woo, P. C. Y. 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). 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 5). 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). Except for specifying that sequences are linear, all settings were kept to their defaults. Google Scholar. In this study, we report the case of a child with severe combined immu presenting a prolonged severe acute respiratory syndrome coronavirus 2 infection. Epidemiology, genetic recombination, and pathogenesis of coronaviruses. Graham, R. L. & Baric, R. S. Recombination, reservoirs, and the modular spike: mechanisms of coronavirus cross-species transmission. 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. For coronaviruses, however, recombination means that small genomic subregions can have independent origins, identifiable if sufficient sampling has been done in the animal reservoirs that support the endemic circulation, co-infection and recombination that appear to be common. 13, e1006698 (2017). 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). PubMed Central PLoS ONE 5, e10434 (2010). We demonstrate that the sarbecoviruses circulating in horseshoe bats have complex recombination histories as reported by others15,20,21,22,23,24,25,26. PureBasic 53 13 constellations Public Python 42 17 Evol. Evol. Eight other BFRs <500nt were identified, and the regions were named BFRAJ in order of length.