pangolin lineage covid pangolin lineage covid

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. 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). A phylogenetic treeusing RAxML v8.2.8 (ref. While there is evidence of positive selection in the sarbecovirus lineage leading to RaTG13/SARS-CoV-2 (ref. Identification of diverse alphacoronaviruses and genomic characterization of a novel severe acute respiratory syndrome-like coronavirus from bats in China. PubMed Central PubMed Biol. Get the most important science stories of the day, free in your inbox. Wu, F. et al. 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. 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. B.W.P. While pangolins could be acting as intermediate hosts for bat viruses to get into humansthey develop severe respiratory disease38 and commonly come into contact with people through traffickingthere is no evidence that pangolin infection is a requirement for bat viruses to cross into humans. Published. Nature 583, 286289 (2020). Epidemiology, genetic recombination, and pathogenesis of coronaviruses. Google Scholar. 3). Humans' selfish, speciesist treatment of these animals could be the very reason why the novel coronavirus exists. Of the nine breakpoints defining these ten BFRs, four showed phylogenetic incongruence (PI) signals with bootstrap support >80%, adopting previously published criteria on using a combination of mosaic and PI signals to show evidence of past recombination events19. Boxes show 95% HPD credible intervals. Indeed, the rates reported by these studies are in line with the short-term SARS rates that we estimate (Fig. PubMed To obtain 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. Collectively our analyses point to bats being the primary reservoir for the SARS-CoV-2 lineage. 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. 88, 70707082 (2014). 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. 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. Intragenomic rearrangements involving 5-untranslated region segments in SARS-CoV-2, other betacoronaviruses, and alphacoronaviruses, Crystal structure of the CoV-Y domain of SARS-CoV-2 nonstructural protein 3, Association of underlying comorbidities and progression of COVID-19 infection amongst 2586 patients hospitalised in the National Capital Region of India: a retrospective cohort study, Molecular characterization of horse nettle virus A, a new member of subgroup B of the genus Nepovirus, Molecular phylogeny of coronaviruses and host receptors among domestic and close-contact animals reveals subgenome-level conservation, crossover, and divergence. 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. Hu, B. et al. 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. Bioinformatics 28, 32483256 (2012). J. Virol. Figure 1 (top) shows the distribution of all identified breakpoints (using 3SEQs exhaustive triplet search) by the number of candidate recombinant sequences supporting them. 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). 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. Pangolin was developed to implement the dynamic nomenclature of SARS-CoV-2 lineages, known as the Pango nomenclature. 382, 11991207 (2020). B 281, 20140732 (2014). However, on closer inspection, the relative divergences in the phylogenetic tree (Fig. Genet. Using a third consensus-based approach for identifying recombinant regions in individual sequenceswith six different recombination detection methods in RDP5 (ref. Google Scholar. When viewing the last 7kb of the genome, a clade of viruses from northern China appears to cluster with sequences from southern Chinese provinces but, when inspecting trees from different parts of ORF1ab, the N. China clade is phylogenetically separated from the S. China clade. Pangolin relies on a novel algorithm called pangoLEARN. 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. Evol. 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. J. Med. & Muhire, B. RDP4: Detection and analysis of recombination patterns in virus genomes. 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 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 . 5. 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. 874850). 56, 152179 (1992). & Holmes, E. C. Recombination in evolutionary genomics. 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 ). The S1 protein of Pangolin-CoV is much more closely related to SARS-CoV-2 than to RaTG13. RegionC showed no PI signals within it. 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). 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. 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. 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. Grey tips correspond to bat viruses, green to pangolin, blue to SARS-CoV and red to SARS-CoV-2. J. Virol. Su, S. et al. All three approaches to removal of recombinant genomic segments point to a single ancestral lineage for SARS-CoV-2 and RaTG13. 3) clusters with viruses from provinces in the centre, east and northeast of China. Suchard, M. A. et al. T.L. Complete genome sequence data were downloaded from GenBank and ViPR; accession numbers of all 68sequences are available in Supplementary Table 4. Nature 558, 180182 (2018). Temporal signal was tested using a recently developed marginal likelihood estimation procedure41 (Supplementary Table 1). Press, 2009). As illustrated by the dashed arrows, these two posteriors motivate our specification of prior distributions with standard deviations inflated 10-fold (light color). Biol. Viruses 11, 979 (2019). with an alignment on which an initial recombination analysis was done. The variable-loop region in SARS-CoV-2 shows closer identity to the 2019 pangolin coronavirus sequence than to the RaTG13 bat virus, supported by phylogenetic inference (Fig. RegionB showed no PI signals within the region, except one including sequence SC2018 (Sichuan), and thus this sequence was also removed from the set. GARD identified eight breakpoints that were also within 50nt of those identified by 3SEQ. 36, 17931803 (2019). 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). 1c). He, B. et al. Use the Previous and Next buttons to navigate the slides or the slide controller buttons at the end to navigate through each slide. 82, 48074811 (2008). 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. Add entries for pangolin-data/-assignment 1.18.1.1 (, Really add a document on testing strategy. "This is an extremely interesting . According to GISAID . Green boxplots show the TMRCA estimate for the RaTG13/SARS-CoV-2 lineage and its most closely related pangolin lineage (Guangdong 2019). This is evidence for numerous recombination events occurring in the evolutionary history of the sarbecoviruses22,33; specifying all past events in their correct temporal order34 is challenging and not shown here. 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. J. Virol. A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. 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 ). 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. volume5,pages 14081417 (2020)Cite this article. Over relatively shallow timescales, such differences can primarily be explained by varying selective pressure, with mildly deleterious variants being eliminated more strongly by purifying selection over longer timescales44,45,46. Lond. As of December 2, 2021, SJdRP, a medium-sized city in the Northwest region of So Paulo state, Brazil (Fig. This leaves the insertion of polybasic. Gorbalenya, A. E. et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. 2a. Specifically, we used a combination of six methods implemented in v.5.5 of RDP5 (ref. Zhou, H. et al. 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. Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus. Genetics 172, 26652681 (2006). Google Scholar. 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. 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. 3). 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.