scholarly journals Bayesian phylodynamic inferences on the temporal evolution and global transmission of SARS-CoV-2

2020 ◽  
Author(s):  
Jianguo Li ◽  
Zhen Li ◽  
Xiaogang Cui ◽  
Changxin Wu
Keyword(s):  
Viral Genome ◽  
Viral Population ◽  
Recent Common Ancestor ◽  
Replication Capacity ◽  
Synonymous Mutations ◽  
Most Recent Common Ancestor ◽  
The Usa ◽  
Bottle Neck ◽  
Clade 1 ◽  
The Uk

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread widely from China to the world. Although the viral genome has been well characterized, the evolutionary origin and global transmission dynamics of SARS-CoV-2 remain poorly investigated. To address this, we retrieved 313 SARS-CoV-2 genomes from the GISAID database (https://www.gisaid.org), from which 99 genomes generated from original clinical specimens with exact collection dates from 16 countries were selected and enrolled for Bayesian phylodynamic analysis. Here we show that the time to the Most Recent Common Ancestor (tMRCA) of SARS-CoV-2 is Dec 11, 2019 (95%HPD, Nov 21 - Dec 24). Two clades of global circulating strains of SARS-CoV-2 were suggested by Bayesian Maximum Clade Credibility (MCC) tree. The USA circulating strains of SARS-CoV-2 seemed to be from both of the two clades, the UK and Australia circulating strains were from Clade 1, the circulating strains in Singapore, Japan, Germany, France, and Italy were from Clade 2. Although we have not found any obvious bottle-neck-effect from the Bayesian Skyline Plot of the viral population dynamics reconstruction, a sharp reduction of the lower 95% HPD of the relative genetic diversity was observed from Feb 5, 2020, suggesting a possible initiation of a bottle-neck-effect. Thirteen (6 synonymous and 7 non-synonymous) mutations in the viral genome were observed, including two clade-specific mutations (C8782T and T1844C in Clade 1 rather than Clade 2) and eleven sub-clade specific mutations. All of the observed mutations occurred in the USA circulating strains, except one mutation T18488C only occurred in the UK circulating strains. A non-synonymous mutation in the 3’-UTR was also observed, suggesting an altered RNA replication capacity of SARS-CoV-2. We thus came to the conclusion that continuous evolution occurred in almost all regions of the SARS-CoV-2 genome and potentially in a country-specific manner. Further efforts on monitoring the genomic mutations of SARS-CoV-2 from different countries are recommended.

scholarly journals Molecular Phylogenesis and Spatiotemporal Spread of SARS-CoV-2 in Southeast Asia

2021 ◽  
Vol 9 ◽  
Author(s):  
Mingjian Zhu ◽  
Jian Shen ◽  
Qianli Zeng ◽  
Joanna Weihui Tan ◽  
Jirapat Kleepbua ◽  
...  
Keyword(s):  
Southeast Asia ◽  
Evolutionary Dynamics ◽  
Phylogenetic Analyses ◽  
Population Expansion ◽  
Principal Component ◽  
Viral Population ◽  
Recent Common Ancestor ◽  
Tropical Region ◽  
Effective Population ◽  
Most Recent Common Ancestor

Background: The ongoing coronavirus disease 2019 (COVID-19) pandemic has posed an unprecedented challenge to public health in Southeast Asia, a tropical region with limited resources. This study aimed to investigate the evolutionary dynamics and spatiotemporal patterns of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the region.Materials and Methods: A total of 1491 complete SARS-CoV-2 genome sequences from 10 Southeast Asian countries were downloaded from the Global Initiative on Sharing Avian Influenza Data (GISAID) database on November 17, 2020. The evolutionary relationships were assessed using maximum likelihood (ML) and time-scaled Bayesian phylogenetic analyses, and the phylogenetic clustering was tested using principal component analysis (PCA). The spatial patterns of SARS-CoV-2 spread within Southeast Asia were inferred using the Bayesian stochastic search variable selection (BSSVS) model. The effective population size (Ne) trajectory was inferred using the Bayesian Skygrid model.Results: Four major clades (including one potentially endemic) were identified based on the maximum clade credibility (MCC) tree. Similar clustering was yielded by PCA; the first three PCs explained 46.9% of the total genomic variations among the samples. The time to the most recent common ancestor (tMRCA) and the evolutionary rate of SARS-CoV-2 circulating in Southeast Asia were estimated to be November 28, 2019 (September 7, 2019 to January 4, 2020) and 1.446 × 10−3 (1.292 × 10−3 to 1.613 × 10−3) substitutions per site per year, respectively. Singapore and Thailand were the two most probable root positions, with posterior probabilities of 0.549 and 0.413, respectively. There were high-support transmission links (Bayes factors exceeding 1,000) in Singapore, Malaysia, and Indonesia; Malaysia involved the highest number (7) of inferred transmission links within the region. A twice-accelerated viral population expansion, followed by a temporary setback, was inferred during the early stages of the pandemic in Southeast Asia.Conclusions: With available genomic data, we illustrate the phylogeography and phylodynamics of SARS-CoV-2 circulating in Southeast Asia. Continuous genomic surveillance and enhanced strategic collaboration should be listed as priorities to curb the pandemic, especially for regional communities dominated by developing countries.

scholarly journals Witnessing Evolution of SARS-CoV-2 through Comparative Phylogenomics: The Proximate Origin is Guangdong, not Wuhan

2020 ◽  
Author(s):  
Özgül Doğan ◽  
Ertan Mahir Korkmaz ◽  
Mahir Budak ◽  
Battal Çıplak ◽  
Hasan Hüseyin Başıbüyük
Keyword(s):  
Exponential Growth ◽  
Viral Genome ◽  
Doubling Time ◽  
Rna Viruses ◽  
Amino Acid Sequences ◽  
Viral Population ◽  
N Gene ◽  
Pandemic Strain ◽  
Synonymous Mutations ◽  
S Gene

A new form of coronavirus called severe acute respiratory disease coronavirus type 2 (SARS-CoV-2) is currently causing a pandemic. A six-month evolutionary history of SARS-CoV-2 is witnessed by characterising the total genome of 821 samples using comparative phylogenomic approaches. Our analyses produced striking inclusive results that may guide scientists/professionals for the past/future of pandemic. Phylogenetic and time estimation analyses suggest the proximate origin of pandemic strain as Guangdong and the origin time as first half of September 2019, not Wuhan and December 2019, respectively. The viral genome experienced a substitution rate similar to other RNA viruses, but it is particularly high in some of the peptides encoding sequences such as leader protein, E gene, orf8, orf10, nsp10, N gene, S gene and M gene and nsp4, while low in nsp11, orf7a, 3C-like proteinase, nsp9, nsp8 and endoRNase. Most strikingly, the divergence rate of amino acid sequences is high proportional to nucleotide divergence. Additionally, specific non-synonymous mutations in nsp3 and nsp6 evolved under positive selection. The exponential growth rate (r), doubling time (Td) and R0 were estimated to be 47.43 per year, 5.39 days and 2.72, respectively. Comparison of synapomorphies distinguishing the SARS-CoV-2 and the candidate ancestor bat coronavirus indicates that mutation pattern in nsp3 and S gene enabled the new strain to invade human and become a pandemic strain. We arrive at the following main conclusions: (i) six months evolution of viral genome is nearly neutral, (ii) origin of pandemic is not Wuhan and predates formal reports, (iii) although viral population is ongoing an exponential growth, the doubling time is evolving towards shortening, and (iv) divergence rate of total genome is similar to other RNA viruses, but it is prominently high in some genes while low in some others and evolution in these genes should be closely monitored as their protein products intervening to pathogenicity, virulence and immune response.

scholarly journals The origin and early spread of SARS-CoV-2 in Europe

2020 ◽  
Author(s):  
Sarah A. Nadeau ◽  
Timothy G. Vaughan ◽  
Jérémie Sciré ◽  
Jana S. Huisman ◽  
Tanja Stadler
Keyword(s):  
Viral Genome ◽  
Geographic Location ◽  
Recent Common Ancestor ◽  
European Regions ◽  
Genome Sequences ◽  
Migration Patterns ◽  
Transmission Event ◽  
Most Recent Common Ancestor ◽  
Geographic Structure ◽  
Migratory Patterns

AbstractThe investigation of migratory patterns of the SARS-CoV-2 pandemic before border closures in Europe is a crucial first step towards an in-depth evaluation of border closure policies. Here we analyze viral genome sequences using a phylodynamic model with geographic structure to estimate the origin and spread of SARS-CoV-2 in Europe prior to border closures. Based on SARS-CoV-2 genomes, we reconstruct a partial transmission tree of the early pandemic, including inferences of the geographic location of ancestral lineages and the number of migration events into and between European regions. We find that the predominant lineage spreading in Europe has a most recent common ancestor in Italy and was probably seeded by a transmission event in either Hubei or Germany. We do not find evidence for preferential migration paths from Hubei into different European regions or from each European region to the others. Sustained local transmission is first evident in Italy and then shortly thereafter in the other European regions considered. Before the first border closures in Europe, we estimate that the rate of occurrence of new cases from within-country transmission was within the bounds of the estimated rate of new cases from migration. In summary, our analysis offers a view on the early state of the epidemic in Europe and on migration patterns of the virus before border closures. This information will enable further study of the necessity and timeliness of border closures.Significance StatementWe estimate the origin and spread of SARS-CoV-2 in Europe prior to border closures based on viral genome sequences using a phylodynamic model with geographic structure. We confirm that the predominant European outbreak most likely started in Italy and spread from there. This outbreak was probably seeded by a transmission event in either Hubei or Germany. In particular, we find that before the first border closures in Europe, the rate of new cases occurring from within-country transmission was within the estimated bounds on the rate of new migration cases.

Molecular Surveillance of HIV-1 Infection in Krasnoyarsk Region, Russia: Epidemiology, Phylodynamics and Phylogeography

2019 ◽  
Vol 17 (2) ◽  
pp. 114-125 ◽  
Author(s):  
Dmitry Neshumaev ◽  
Aleksey Lebedev ◽  
Marina Malysheva ◽  
Anatoly Boyko ◽  
Sergey Skudarnov ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Temporal Dynamics ◽  
Phylogenetic Reconstruction ◽  
Viral Population ◽  
Recent Common Ancestor ◽  
Krasnoyarsk Region ◽  
Most Recent Common Ancestor ◽  
And Migration ◽  
Viral Lineage ◽  
Hiv 1

Background:The information about the dynamics of the viral population and migration events that affect the epidemic in different parts of the Russia is insufficient. Possibly, the huge size of the country and limited transport accessibility to certain territories may determine unique traits of the HIV-1 evolutionary history in different regions.Objective:The aim of this study was to explore the genetic diversity of HIV-1 in the Krasnoyarsk region and reconstruct spatial-temporal dynamics of the infection in the region.Methods:The demographic and virologic data from 281 HIV-infected individuals in Krasnoyarsk region collected during 2011-2016 were analyzed. The time to the most recent common ancestor, evolutionary rates, population growth, and ancestral geographic movements was estimated using Bayesian coalescent-based methods.Results:The study revealed moderate diversity of the HIV-1 subtypes found in the region, which included A6 (92.3%), CRF063_02A (4.3%), B (1.1%), and unique recombinants (2.5%). Phylogenetic reconstruction revealed that the A6 subtype was introduced into Krasnoyarsk region by one viral lineage, which arose around 1996.9 (1994.5-1999.5). The phylogeography analysis pointed to Krasnoyarsk city as the geographical center of the epidemic, which further spread to central neighboring districts of the region. At least two epidemic growth phases of subtype A6 were identified which included exponential growth in early-2000s followed by the decline in the mid/late 2010s.Conclusion:This study demonstrates a change in the genetic diversity of HIV-1 in the Krasnoyarsk region. At the beginning of the epidemic, subtype A6 prevailed, subtypes B and CRF063_02A appeared in the region later.

scholarly journals Synonymous mutations and the molecular evolution of SARS-Cov-2 origins

2020 ◽  
Author(s):  
Hongru Wang ◽  
Lenore Pipes ◽  
Rasmus Nielsen
Keyword(s):  
Amino Acid ◽  
Negative Impact ◽  
Protein A ◽  
Viral Fitness ◽  
Recent Common Ancestor ◽  
Synonymous Divergence ◽  
Synonymous Mutations ◽  
Most Recent Common Ancestor ◽  
High Amino Acid ◽  
Amino Acid Divergence

AbstractHuman severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is most closely related, by average genetic distance, to two coronaviruses isolated from bats, RaTG13 and RmYN02. However, there is a segment of high amino acid similarity between human SARS-CoV-2 and a pangolin isolated strain, GD410721, in the receptor binding domain (RBD) of the spike protein, a pattern that can be caused by either recombination or by convergent amino acid evolution driven by natural selection. We perform a detailed analysis of the synonymous divergence, which is less likely to be affected by selection than amino acid divergence, between human SARS-CoV-2 and related strains. We show that the synonymous divergence between the bat derived viruses and SARS-CoV-2 is larger than between GD410721 and SARS-CoV-2 in the RBD, providing strong additional support for the recombination hypothesis. However, the synonymous divergence between pangolin strain and SARS-CoV-2 is also relatively high, which is not consistent with a recent recombination between them, instead it suggests a recombination into RaTG13. We also find a 14-fold increase in the dN/dS ratio from the lineage leading to SARS-CoV-2 to the strains of the current pandemic, suggesting that the vast majority of non-synonymous mutations currently segregating within the human strains have a negative impact on viral fitness. Finally, we estimate that the time to the most recent common ancestor of SARS-CoV-2 and RaTG13 or RmYN02 based on synonymous divergence, is 51.71 years (95% C.I., 28.11-75.31) and 37.02 years (95% C.I., 18.19-55.85), respectively.

scholarly journals An application of population genetic theory to synonymous gene sequence evolution in the human immunodeficiency virus (HIV)

1994 ◽  
Vol 64 (1) ◽  
pp. 1-9 ◽  
Author(s):  
John K. Kelly
Keyword(s):  
Human Immunodeficiency Virus ◽  
Mutation Rate ◽  
Population Genetic ◽  
Gene Sequence ◽  
High Rate ◽  
Viral Population ◽  
Recent Common Ancestor ◽  
Synonymous Mutations ◽  
Immunodeficiency Virus ◽  
Hiv 1

SummaryA population genetic model is developed and then applied to the synonymous gene sequence variation observed in samples of the Human Immunodeficiency Virus Type 1 (HIV-1). The samples, which were taken from several previous studies, contain sequences of the envelope glycoprotein gene (gp 120) of HIV-1. This analysis suggests that the viral population within an infected patient at any specific time is likely to be composed of close relatives. The viruses in a sample are likely to share a recent common ancestor probably due to consistent positive selection for non-synonymous mutations coupled with low recombination in this region of the genome. There is no substantial difference in synonymous evolutionary rate between samples of sequences obtained from Peripheral Blood Mononucleate Cells (PBMCs) and samples taken from blood plasma. This is likely to be due to the high rate of migration between these 2 HIV sub-populations. The mutation rate for the genetic region examined is estimated at 9·20 × 10−4per site per month. Under the assumptions of the estimation procedure, this estimate can be bounded between 8·50 and 9·91 × 10−4with 95% confidence. When coupled with direct estimates of mutation rate, the rate of synonymous evolution suggests that the mean number of generations per month for HIV-1in vivois between 1 and 4.

scholarly journals The Algerian Chapter of SARS-CoV-2 Pandemic: An Evolutionary, Genetic, and Epidemiological Prospect

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1525
Author(s):  
Safia Zeghbib ◽  
Balázs A. Somogyi ◽  
Brigitta Zana ◽  
Gábor Kemenesi ◽  
Róbert Herczeg ◽  
...  
Keyword(s):  
Amino Acid ◽  
Common Ancestor ◽  
Genomic Analysis ◽  
Amino Acid Replacement ◽  
Mitigation Measures ◽  
Recent Common Ancestor ◽  
Multiple Introductions ◽  
Most Recent Common Ancestor ◽  
The Usa ◽  
Nsp3 Gene

To explore the SARS-CoV-2 pandemic in Algeria, a dataset comprising ninety-five genomes originating from SARS-CoV-2 sampled from Algeria and other countries worldwide, from 24 December 2019, through 4 March 2021, was thoroughly examined. While performing a multi-component analysis regarding the Algerian outbreak, the toolkit of phylogenetic, phylogeographic, haplotype, and genomic analysis were effectively implemented. We estimated the Time to the Most Recent Common Ancestor (TMRCA) in reference to the Algerian pandemic and highlighted the multiple introductions of the disease and the missing data depicted in the transmission loop. In addition, we emphasized the significant role played by local and international travels in disease dissemination. Most importantly, we unveiled mutational patterns, the effect of unique mutations on corresponding proteins, and the relatedness regarding the Algerian sequences to other sequences worldwide. Our results revealed individual amino-acid replacements such as the deleterious replacement A23T in the orf3a gene in Algeria_EPI_ISL_418241. Additionally, a connection between Algeria_EPI_ISL_420037 and sequences originating from the USA was observed through a USA characteristic amino-acid replacement T1004I in the nsp3 gene, found in the aforementioned Algerian sequence. Similarly, successful tracing could be established, such as Algeria/G37318-8849/2020|EPI_ISL_766863, which was imported from Saudi Arabia during the pilgrimage. Lastly, we assessed the Algerian mitigation measures regarding disease containment using statistical analyses.

scholarly journals Synonymous mutations and the molecular evolution of SARS-CoV-2 origins

2020 ◽  
Author(s):  
Hongru Wang ◽  
Lenore Pipes ◽  
Rasmus Nielsen
Keyword(s):  
Amino Acid ◽  
Negative Impact ◽  
Protein A ◽  
Viral Fitness ◽  
Recent Common Ancestor ◽  
Synonymous Divergence ◽  
Synonymous Mutations ◽  
Most Recent Common Ancestor ◽  
High Amino Acid ◽  
Amino Acid Divergence

Abstract Human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is most closely related, by average genetic distance, to two coronaviruses isolated from bats, RaTG13 and RmYN02. However, there is a segment of high amino acid similarity between human SARS-CoV-2 and a pangolin-isolated strain, GD410721, in the receptor-binding domain (RBD) of the spike protein, a pattern that can be caused by either recombination or by convergent amino acid evolution driven by natural selection. We perform a detailed analysis of the synonymous divergence, which is less likely to be affected by selection than amino acid divergence, between human SARS-CoV-2 and related strains. We show that the synonymous divergence between the bat-derived viruses and SARS-CoV-2 is larger than between GD410721 and SARS-CoV-2 in the RBD, providing strong additional support for the recombination hypothesis. However, the synonymous divergence between pangolin strain and SARS-CoV-2 is also relatively high, which is not consistent with a recent recombination between them, instead, it suggests a recombination into RaTG13. We also find a 14-fold increase in the dN/dS ratio from the lineage leading to SARS-CoV-2 to the strains of the current pandemic, suggesting that the vast majority of nonsynonymous mutations currently segregating within the human strains have a negative impact on viral fitness. Finally, we estimate that the time to the most recent common ancestor of SARS-CoV-2 and RaTG13 or RmYN02 based on synonymous divergence is 51.71 years (95% CI, 28.11–75.31) and 37.02 years (95% CI, 18.19–55.85), respectively.

scholarly journals Birth of an order: comprehensive molecular phylogenetic study excludes Herpomyces (Fungi, Laboulbeniomycetes) from Laboulbeniales

2019 ◽  
Author(s):  
Danny Haelewaters ◽  
Walter P. Pfliegler ◽  
Michał Gorczak ◽  
Donald H. Pfister
Keyword(s):  
Molecular Data ◽  
Recent Common Ancestor ◽  
Phylogenetic Study ◽  
New Order ◽  
Most Recent Common Ancestor ◽  
Molecular Phylogenetic Study ◽  
Molecular Phylogenetic ◽  
The Usa ◽  
Single Genus ◽  
Morphological And Molecular Data

The class Laboulbeniomycetes comprises biotrophic parasites associated with arthropods and fungi. Two orders are currently recognized, Pyxidiophorales and Laboulbeniales. Herpomyces is an isolated genus of Laboulbeniales, with species that exclusively parasitize cockroaches (Blattodea). Here, we evaluate 39 taxa of Laboulbeniomycetes with a three-locus phylogeny (nrSSU, ITS, nrLSU) and propose a new order in this class. Herpomycetales accommodates a single genus, Herpomyces, with currently 26 species, one of which is described here based on morphological and molecular data. Herpomyces shelfordellae is found on Shelfordella lateralis cockroaches from Hungary, Poland, and the USA. We also build on the six-locus dataset from the Ascomycota Tree of Life paper (Schoch and colleagues, 2009) to confirm that Laboulbeniomycetes and Sordariomycetes are sister classes, and we apply laboulbeniomyceta as a rankless taxon for the now well-resolved node that describes the most recent common ancestor of both classes.

scholarly journals In-frame seven amino-acid duplication in AIP arose over the last 3000 years, disrupts protein interaction and stability and is associated with gigantism

2017 ◽  
Vol 177 (3) ◽  
pp. 257-266 ◽  
Author(s):  
Roberto Salvatori ◽  
Serban Radian ◽  
Yoan Diekmann ◽  
Donato Iacovazzo ◽  
Alessia David ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Amino Acid ◽  
Protein Stability ◽  
Protein Interactions ◽  
Common Ancestor ◽  
Recent Common Ancestor ◽  
Interacting Protein ◽  
Aryl Hydrocarbon ◽  
Most Recent Common Ancestor ◽  
The Uk

Objective Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are associated with pituitary adenoma, acromegaly and gigantism. Identical alleles in unrelated pedigrees could be inherited from a common ancestor or result from recurrent mutation events. Design and methods Observational, inferential and experimental study, including: AIP mutation testing; reconstruction of 14 AIP-region (8.3 Mbp) haplotypes; coalescent-based approximate Bayesian estimation of the time to most recent common ancestor (tMRCA) of the derived allele; forward population simulations to estimate current number of allele carriers; proposal of mutation mechanism; protein structure predictions; co-immunoprecipitation and cycloheximide chase experiments. Results Nine European-origin, unrelated c.805_825dup-positive pedigrees (four familial, five sporadic from the UK, USA and France) included 16 affected (nine gigantism/four acromegaly/two non-functioning pituitary adenoma patients and one prospectively diagnosed acromegaly patient) and nine unaffected carriers. All pedigrees shared a 2.79 Mbp haploblock around AIP with additional haploblocks privately shared between subsets of the pedigrees, indicating the existence of an evolutionarily recent common ancestor, the ‘English founder’, with an estimated median tMRCA of 47 generations (corresponding to 1175 years) with a confidence interval (9–113 generations, equivalent to 225–2825 years). The mutation occurred in a small tandem repeat region predisposed to slipped strand mispairing. The resulting seven amino-acid duplication disrupts interaction with HSP90 and leads to a marked reduction in protein stability. Conclusions The c.805_825dup allele, originating from a common ancestor, associates with a severe clinical phenotype and a high frequency of gigantism. The mutation is likely to be the result of slipped strand mispairing and affects protein–protein interactions and AIP protein stability.

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