pangolin lineage covid

A third approach attempted to minimize the number of regions removed while also minimizing signals of mosaicism and homoplasy. Extensive diversity of coronaviruses in bats from China. PubMed Removal of five sequences that appear to be recombinants and two small subregions of BFRA was necessary to ensure that there were no phylogenetic incongruence signals among or within the three BFRs. All four of these breakpoints were also identified with the tree-based recombination detection method GARD35. b, Similarity plot between SARS-CoV-2 and several selected sequences including RaTG13 (black), SARS-CoV (pink) and two pangolin sequences (orange). 30, 21962203 (2020). 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. B.W.P. In regionA, we removed subregion A1 (ntpositions 3,8724,716 within regionA) and subregion A4 (nt1,6422,113) because both showed PI signals with other subregions of regionA. is funded by the MRC (no. Virological.org http://virological.org/t/ncov-2019-codon-usage-and-reservoir-not-snakes-v2/339 (2020). Mol. Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins. Pango lineage designation and assignment using SARS-CoV-2 - PubMed Coronavirus Software Tools - Illumina, Inc. 2a. Originally, PANGOLIN used a maximum-likelihood-based assignment algorithm to assign query SARS-CoV-2 the most likely lineage sequence. Mol. Boni, M. F., Zhou, Y., Taubenberger, J. K. & Holmes, E. C. Homologous recombination is very rare or absent in human influenza A virus. Martin, D. P., Murrell, B., Golden, M., Khoosal, A. Biol. Identifying SARS-CoV-2-related coronaviruses in Malayan pangolins. Med. To avoid artefacts due to recombination, we focused on NRR1 and NRR2 and the recombination-masked alignment NRA3 to infer time-measured evolutionary histories. Our most conservative approach attempted to ensure that putative NRRs had no mosaic or phylogenetic incongruence signals. 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. Pangolins: What are they and why are they linked to Covid-19? - Inverse GARD identified eight breakpoints that were also within 50nt of those identified by 3SEQ. 2). CAS Provided by the Springer Nature SharedIt content-sharing initiative, Molecular and Cellular Biochemistry (2023), Nature Microbiology (Nat Microbiol) . Bryant, D. & Moulton, V. Neighbor-Net: an agglomerative method for the construction of phylogenetic networks. This produced non-recombining alignment NRA3, which included 63 of the 68genomes. Due to the absence of temporal signal in the sarbecovirus datasets, we used informative prior distributions on the evolutionary rate to estimate divergence dates. & Li, X. Crossspecies transmission of the newly identified coronavirus 2019nCoV. Softw. Biol. Indeed, the rates reported by these studies are in line with the short-term SARS rates that we estimate (Fig. a, Breakpoints identified by 3SEQ illustrated by percentage of sequences (out of 68) that support a particular breakpoint position. the development of viral diversity. Uncertainty measures are shown in Extended Data Fig. cov-lineages/pangolin - GitHub 36, 17931803 (2019). Published. 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. In March, when covid cases began spiking around India, Bani Jolly went hunting for answers in the virus's genetic code. For the HCoV-OC43, MERS-CoV and SARS datasets we specified flexible skygrid coalescent tree priors. This commit does not belong to any branch on this repository, and may belong to a fork outside of the repository. Host ecology determines the dispersal patterns of a plant virus. Transparent bands of interquartile range width and with the same colours are superimposed to highlight the overlap between estimates. Stamatakis, A. RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models. 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. MC_UU_1201412). 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. Identification of diverse alphacoronaviruses and genomic characterization of a novel severe acute respiratory syndrome-like coronavirus from bats in China. 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. Extended Data Fig. Even before the COVID-19 pandemic, pangolins have been making headlines. Using a third consensus-based approach for identifying recombinant regions in individual sequenceswith six different recombination detection methods in RDP5 (ref. 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. It is available as a command line tool and a web application. 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. (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). 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. Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage - Nature The shaded region corresponds to the Sprotein. & Minh, B. Q. IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies. While there is evidence of positive selection in the sarbecovirus lineage leading to RaTG13/SARS-CoV-2 (ref. 1a-c ), has the third-highest number of confirmed COVID-19 cases in the state of So. Mol. Lond. 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 SARS-CoV-2 is an appropriate name for the new coronavirus. 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 ). 2, vew007 (2016). Evolutionary rate estimation can be profoundly affected by the presence of recombination50. Lam, H. M., Ratmann, O. volume5,pages 14081417 (2020)Cite this article. Unfortunately, a response that would achieve containment was not possible. Suchard, M. A. et al. from the European Research Council under the European Unions Horizon 2020 research and innovation programme (grant agreement no. Nat. Sequences are colour-coded by province according to the map. Epidemiology, genetic recombination, and pathogenesis of coronaviruses. 4), but also by markedly different evolutionary rates. 5). Abstract. wrote the first draft of the manuscript, and all authors contributed to manuscript editing. 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. Many Git commands accept both tag and branch names, so creating this branch may cause unexpected behavior. Posterior rate distributions for MERS-CoV (far left) and HCoV-OC43 (far right) using BEAST on n=27 sequences spread over 4 years (MERS-CoV) and n=27 sequences spread over 49 years (HCoV-OC43). 82, 18191826 (2008). 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. Wu, F. et al. Open reading frames are shown above the breakpoint plot, with the variable-loop region indicated in the Sprotein. 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. Don't blame pangolins, coronavirus family tree tracing could prove key 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. 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. 4, vey016 (2018). 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. Evol. Li, X. et al. Split diversity in constrained conservation prioritization using integer linear programming. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. 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. 4. Frontiers | Novel Highly Divergent SARS-CoV-2 Lineage With the Spike 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. The relatively fast evolutionary rate means that it is most appropriate to estimate shallow nodes in the sarbecovirus evolutionary history. 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 87, 62706282 (2013). Dudas, G., Carvalho, L. M., Rambaut, A. Identifying SARS-CoV-2 related coronaviruses in Malayan pangolins 35, 247251 (2018). 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. This is not surprising for diverse viral populations with relatively deep evolutionary histories. Menachery, V. D. et al. If the latter still identified non-negligible recombination signal, we removed additional genomes that were identified as major contributors to the remaining signal. The idea is that pangolins carrying the virus, SARS-CoV-2, came into contact with humans. 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. Viral metagenomics revealed Sendai virus and coronavirus infection of Malayan pangolins (Manis javanica). Nguyen, L.-T., Schmidt, H. A., Von Haeseler, A. 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. Lancet 395, 565574 (2020). 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 . A., Lytras, S., Singer, J. Nature 538, 193200 (2016). Coronavirus origins: genome analysis suggests two viruses may have combined Five example sequences with incongruent phylogenetic positions in the two trees are indicated by dashed lines. 88, 70707082 (2014). 382, 11991207 (2020). J. Virol. & Holmes, E. C. A genomic perspective on the origin and emergence of SARS-CoV-2. RegionB is 5,525nt long. More evidence Pangolin not intermediary in transmission of SARS-CoV-2 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. Bruen, T. C., Philippe, H. & Bryant, D. A simple and robust statistical test for detecting the presence of recombination. Our third approach involved identifying breakpoints and masking minor recombinant regions (with gaps, which are treated as unobserved characters in probabilistic phylogenetic approaches). 6, eabb9153 (2020). 95% credible interval bars are shown for all internal node ages. 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. Trends Microbiol. BEAST inferences made use of the BEAGLE v.3 library68 for efficient likelihood computations. Chernomor, O. et al. 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. Annu Rev. Google Scholar. Zhou, P. et al. 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). 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. Identifying SARS-CoV-2-related coronaviruses in Malayan pangolins 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. 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. PDF How COVID-19 Variants Get Their Name - doh.wa.gov A new SARS-CoV-2 variant (B.1.1.523) capable of escaping immune protections Of the countries that have contributed SARS-CoV-2 data, 30% had genomes of this lineage. With horseshoe bats currently the most plausible origin of SARS-CoV-2, it is important to consider that sarbecoviruses circulate in a variety of horseshoe bat species with widely overlapping species ranges57. 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. This study provides an integration of existing classifications and describes evolutionary trends of the SARS-CoV . 36, 7597 (2002). Influenza viruses reassort17 but they do not undergo homologous recombination within RNA segments18,19, meaning that origins questions for influenza outbreaks can always be reduced to origins questions for each of influenzas eight RNA segments. Pangolin was developed to implement the dynamic nomenclature of SARS-CoV-2 lineages, known as the Pango nomenclature. The Sichuan (SC2018) virus appears to be a recombinant of northern/central and southern viruses, while the two Zhejiang viruses (CoVZXC21 and CoVZC45) appear to carry a recombinant region from southern or central China. G066215N, G0D5117N and G0B9317N)) and by the European Unions Horizon 2020 project MOOD (no. Grey tips correspond to bat viruses, green to pangolin, blue to SARS-CoV and red to SARS-CoV-2. This underscores the need for a global network of real-time human disease surveillance systems, such as that which identified the unusual cluster of pneumonia in Wuhan in December 2019, with the capacity to rapidly deploy genomic tools and functional studies for pathogen identification and characterization. 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. You are using a browser version with limited support for CSS. 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. 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). D.L.R. Sarbecovirus, HCoV-OC43 and SARS-CoV data were assembled from GenBank to be as complete as possible, with sampling year as an inclusion criterion. These datasets were subjected to the same recombination masking approach as NRA3 and were characterized by a strong temporal signal (Fig. 90, 71847195 (2016). Without better sampling, however, it is impossible to estimate whether or how many of these additional lineages exist. 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. Current sampling of pangolins does not implicate them as an intermediate host. Google Scholar. 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. 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. Collectively our analyses point to bats being the primary reservoir for the SARS-CoV-2 lineage. Preprint at https://doi.org/10.1101/2020.02.10.942748 (2020). 5 (NRR1) are conservative in the sense that NRR1 is more likely to be non-recombinant than NRR2 or NRA3. Wang, H., Pipes, L. & Nielsen, R. Synonymous mutations and the molecular evolution of SARS-Cov-2 origins. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. 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). 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. ac, Root-to-tip (RtT) divergence as a function of sampling time for the three coronavirus evolutionary histories unfolding over different timescales (HCoV-OC43 (n=37; a) MERS (n=35; b) and SARS (n=69; c)). Microbiol. & Bedford, T. MERS-CoV spillover at the camelhuman interface. A tag already exists with the provided branch name. 94, e0012720 (2020). 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. Current Overview on Disease and Health Research Vol. 6 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. Biol. Bayesian evolutionary rate and divergence date estimates were shown to be consistent for these three approaches and for two different prior specifications of evolutionary rates based on HCoV-OC43 and MERS-CoV. Adv. 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