Comparative Genomic Analyses Reveal a Specific Mutation Pattern Between Human Coronavirus SARS-CoV-2 and Bat-CoV RaTG13

BackgroundThe outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, rapidly grew into a global pandemic. How SARS-CoV-2 evolved remains unclear.MethodsWe performed a comprehensive analysis using the available genomes of SARS-CoV-2 and its closely related coronaviruses.ResultsThe ratio of nucleotide substitutions to amino acid substitutions of the spike gene (9.07) between SARS-CoV-2 WIV04 and Bat-CoV RaTG13 was markedly higher than that between other coronaviruses (range, 1.29–4.81); the ratio of non-synonymous to synonymous substitution rates (dN/dS) between SARS-CoV-2 WIV04 and Bat-CoV RaTG13 was the lowest among all the performed comparisons, suggesting evolution under stringent selective pressure. Notably, the relative proportion of the T:C transition was markedly higher between SARS-CoV-2 WIV04 and Bat-CoV RaTG13 than between other compared coronaviruses. Codon usage is similar across these coronaviruses and is unlikely to explain the increased number of synonymous mutations. Moreover, some sites of the spike protein might be subjected to positive selection.ConclusionsOur results showed an increased proportion of synonymous substitutions and the T:C transition between SARS-CoV-2 and RaTG13. Further investigation of the mutation pattern mechanism would contribute to understanding viral pathogenicity and its adaptation to hosts.

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Comparative genomic analysis revealed specific mutation pattern between human coronavirus SARS-CoV-2 and Bat-SARSr-CoV RaTG13

10.1101/2020.02.27.969006 ◽

2020 ◽

Cited By ~ 14

Author(s):

Longxian Lv ◽

Gaolei Li ◽

Jinhui Chen ◽

Xinle Liang ◽

Yudong Li

Keyword(s):

Amino Acid ◽

Genomic Analysis ◽

Synonymous Substitution ◽

Neutral Evolution ◽

Comparative Genomic ◽

Nucleotide Substitutions ◽

Evolutionary Mechanisms ◽

Spike Gene ◽

Synonymous Mutations ◽

Mutation Pattern

AbstractThe novel coronavirus SARS-CoV-2 (2019-nCoV) is a member of the family coronaviridae and contains a single-stranded RNA genome with positive-polarity. To reveal the evolution mechanism of SARS-CoV-2 genome, we performed comprehensive genomic analysis with newly sequenced SARS-CoV-2 strains and 20 closely related coronavirus strains. Among 98 nucleotide mutations at 93 sites of the genome among different SARS-CoV-2 strains, 58 of them caused amino acid change, indicating a result of neutral evolution. However, the ratio of nucleotide substitutions to amino acid substitutions of spike gene (9.07) between SARS-CoV-2 WIV04 and Bat-SARSr-CoV RaTG13 was extensively higher than those from comparisons between other coronaviruses (range 1.29 - 4.81). The elevated synonymous mutations between SARS-CoV-2 and RaTG13, suggesting they underwent stronger purifying selection. Moreover, their nucleotide substitutions are enriched with T:C transition, which is consistent with the mutation signature caused by deactivity of RNA 3’-to-5’ exoribonuclease (ExoN). The codon usage was similar between SARS-CoV-2 and other strains in beta-coronavirus lineage B, suggesting it had small impact on the mutation pattern. In comparison of SARS-CoV-2 WIV04 with Bat-SARSr-CoV RaTG13, the ratios of non-synonymous to synonymous substitution rates (dN/dS) was the lowest among all performed comparisons, reconfirming the evolution of SARS-CoV-2 under stringent selective pressure. Moreover, some sites of spike protein might be subjected to positive selection. Therefore, our results will help understanding the evolutionary mechanisms contribute to viral pathogenicity and its adaptation with hosts.

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Potent Antibody-Mediated Neutralization and Evolution of Antigenic Escape Variants of Simian Immunodeficiency Virus Strain SIVmac239 In Vivo

Journal of Virology ◽

10.1128/jvi.00871-08 ◽

2008 ◽

Vol 82 (19) ◽

pp. 9739-9752 ◽

Cited By ~ 18

Author(s):

Shuji Sato ◽

Eloisa Yuste ◽

William A. Lauer ◽

Eun Hyuk Chang ◽

Jennifer S. Morgan ◽

...

Keyword(s):

Amino Acid ◽

Time Course ◽

Neutralizing Antibody ◽

Synonymous Substitution ◽

Viral Envelope ◽

Single Amino Acid ◽

Nucleotide Substitutions ◽

Recombinant Viruses ◽

Synonymous Substitution Rates

ABSTRACT Here, we describe the evolution of antigenic escape variants in a rhesus macaque that developed unusually high neutralizing antibody titers to SIVmac239. By 42 weeks postinfection, 50% neutralization of SIVmac239 was achieved with plasma dilutions of 1:1,000. Testing of purified immunoglobulin confirmed that the neutralizing activity was antibody mediated. Despite the potency of the neutralizing antibody response, the animal displayed a typical viral load profile and progressed to terminal AIDS with a normal time course. Viral envelope sequences from week 16 and week 42 plasma contained an excess of nonsynonymous substitutions, predominantly in V1 and V4, including individual sites with ratios of nonsynonymous to synonymous substitution rates (dN/dS) highly suggestive of strong positive selection. Recombinant viruses encoding envelope sequences isolated from these time points remained resistant to neutralization by all longitudinal plasma samples, revealing the failure of the animal to mount secondary responses to the escaped variants. Substitutions at two sites with significant dN/dS values, one in V1 and one in V4, were independently sufficient to confer nearly complete resistance to neutralization. Substitutions at three additional sites, one in V4 and two in gp41, conferred moderate to high levels of resistance when tested individually. All the amino acid changes leading to escape resulted from single nucleotide substitutions. The observation that antigenic escape resulted from individual, single amino acid replacements at sites well separated in current structural models of Env indicates that the virus can utilize multiple independent pathways to rapidly achieve similar levels of resistance.

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Unbiased estimate of synonymous and non-synonymous substitution rates with non-stationary base composition

10.1101/124925 ◽

2017 ◽

Cited By ~ 4

Author(s):

Laurent Guéguen ◽

Laurent Duret

Keyword(s):

Base Composition ◽

Evolutionary Process ◽

Synonymous Substitution ◽

Substitution Rates ◽

Synonymous Mutations ◽

Synonymous Substitution Rates ◽

Good Proxy ◽

Neutral Mutations ◽

Stochastic Mapping ◽

Codon Evolution

AbstractThe measure of synonymous and non-synonymous substitution rates (dS and dN) is useful for assessing selection operating on protein sequences or for investigating mutational processes affecting genomes. In particular, the ratio is expected to be a good proxy of ω, the probability of fixation of non-synonymous mutations relative to that of neutral mutations. Standard methods for estimating dN, dS or ω rely on the assumption that the base composition of sequences is at the equilibrium of the evolutionary process. In many clades, this assumption of stationarity is in fact incorrect, and we show here through simulations and through analyses of empirical data that non-stationarity biases the estimate of dN, dS and ω. We show that the bias in the estimate of ω can be fixed by explicitly considering non-stationarity in the modeling of codon evolution, in a maximum likelihood framework. Moreover, we propose an exact method of estimate of dN and dS on branches, based on stochastic mapping, that can take into account non-stationarity. This method can be directly applied to any kind of model of evolution of codons, as long as neutrality is clearly parameterized.

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Detecting positive selection within genomes: the problem of biased gene conversion

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2010.0007 ◽

2010 ◽

Vol 365 (1552) ◽

pp. 2571-2580 ◽

Cited By ~ 86

Author(s):

Abhirami Ratnakumar ◽

Sylvain Mousset ◽

Sylvain Glémin ◽

Jonas Berglund ◽

Nicolas Galtier ◽

...

Keyword(s):

Positive Selection ◽

Gene Conversion ◽

Evolutionary Genetics ◽

Synonymous Substitution ◽

Nucleotide Substitutions ◽

Accelerated Evolution ◽

A Genome ◽

Biased Gene Conversion ◽

Synonymous Substitution Rates ◽

Wide Scale

The identification of loci influenced by positive selection is a major goal of evolutionary genetics. A popular approach is to perform scans of alignments on a genome-wide scale in order to find regions evolving at accelerated rates on a particular branch of a phylogenetic tree. However, positive selection is not the only process that can lead to accelerated evolution. Notably, GC-biased gene conversion (gBGC) is a recombination-associated process that results in the biased fixation of G and C nucleotides. This process can potentially generate bursts of nucleotide substitutions within hotspots of meiotic recombination. Here, we analyse the results of a scan for positive selection on genes on branches across the primate phylogeny. We show that genes identified as targets of positive selection have a significant tendency to exhibit the genomic signature of gBGC. Using a maximum-likelihood framework, we estimate that more than 20 per cent of cases of significantly elevated non-synonymous to synonymous substitution rates ratio ( d N / d S ), particularly in shorter branches, could be due to gBGC. We demonstrate that in some cases, gBGC can lead to very high d N / d S (more than 2). Our results indicate that gBGC significantly affects the evolution of coding sequences in primates, often leading to patterns of evolution that can be mistaken for positive selection.

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Synonymous Rates at the RpII215 Gene of Drosophila: Variation Among Species and Across the Coding Region

Genetics ◽

10.1093/genetics/152.1.269 ◽

1999 ◽

Vol 152 (1) ◽

pp. 269-280 ◽

Cited By ~ 2

Author(s):

Ana Llopart ◽

Montserrat Aguadé

Keyword(s):

Rna Polymerase Ii ◽

Molecular Clock ◽

Constitutive Expression ◽

Synonymous Substitution ◽

Coding Region ◽

Substitution Rates ◽

Synonymous Mutations ◽

Molecular Clock Hypothesis ◽

Synonymous Substitution Rates ◽

Clock Hypothesis

Abstract The region encompassing the RpII215 gene that encodes the largest component of the RNA polymerase II complex (1889 amino acids) has been sequenced in Drosophila subobscura, D. madeirensis, D. guanche, and D. pseudoobscura. Nonsynonymous divergence estimates (Ka) indicate that this gene has a very low rate of amino acid replacements. Given its low Ka and constitutive expression, synonymous substitution rates are, however, unexpectedly high. Sequence comparisons have allowed the molecular clock hypothesis to be tested. D. guanche is an insular species and it is therefore expected to have a reduced effective size relative to D. subobscura. The significantly higher rate of synonymous substitutions detected in the D. guanche lineage could be explained if synonymous mutations behave as nearly neutral. Significant departure from the molecular clock hypothesis for synonymous and nonsynonymous substitutions was detected when comparing the D. subobscura, D. pseudoobscura, and D. melanogaster lineages. Codon bias and synonymous divergence between D. subobscura and D. melanogaster were negatively correlated across the RpII215 coding region, which indicates that selection coefficients for synonymous mutations vary across the gene. The C-terminal domain (CTD) of the RpII215 protein is structurally and functionally differentiated from the rest of the protein. Synonymous substitution rates were significantly different in both regions, which strongly indicates that synonymous mutations in the CTD and in the non-CTD regions are under detectably different selection coefficients.

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Rates of synonymous substitution and base composition of nuclear genes in Drosophila.

Genetics ◽

10.1093/genetics/130.4.855 ◽

1992 ◽

Vol 130 (4) ◽

pp. 855-864

Author(s):

E N Moriyama ◽

T Gojobori

Keyword(s):

Nuclear Genome ◽

Nuclear Gene ◽

Synonymous Substitution ◽

Selective Constraint ◽

Nuclear Genes ◽

Functional Genes ◽

Silent Substitution ◽

Codon Positions ◽

Synonymous Substitution Rates ◽

Mutation Pattern

Abstract We compared the rates of synonymous (silent) substitution among various genes in a number of species of Drosophila. First, we found that even for a particular gene, the rate of synonymous substitution varied considerably with Drosophila lineages. Second, we showed a large variation in synonymous substitution rates among nuclear genes in Drosophila. These rates of synonymous substitution were correlated negatively with C content and positively with A content at the third codon positions. Nucleotide sequences were also compared between pseudogenes and their functional homologs. The C content of the pseudogenes was lower than that of the functional genes and the A content of the former was higher than that of the latter. Because the synonymous substitution for functional genes and the nucleotide substitution for pseudogenes are exempted from any selective constraint at the protein level, these observations could be explained by a biased pattern of mutation in the Drosophila nuclear genome. Such a bias in the mutation pattern may affect the molecular clock (local clock) of each nuclear gene of each species. Finally, we obtained the average rates of synonymous substitution for three gene groups in Drosophila; 11.0 x 10(-9), 17.5 x 10(-9) and 27.1 x 10(-9)/site/year.

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The domestication of Cucurbita argyrosperma as revealed by the genome of its wild relative

Horticulture Research ◽

10.1038/s41438-021-00544-9 ◽

2021 ◽

Vol 8 (1) ◽

Author(s):

Josué Barrera-Redondo ◽

Guillermo Sánchez-de la Vega ◽

Jonás A. Aguirre-Liguori ◽

Gabriela Castellanos-Morales ◽

Yocelyn T. Gutiérrez-Guerrero ◽

...

Keyword(s):

Defense Mechanisms ◽

Population Level ◽

Growth Hormones ◽

Comparative Genomic ◽

Structural Variants ◽

Closely Related Species ◽

Level Data ◽

Genomic Analyses ◽

Genotype By Sequencing ◽

Regulation Of Growth

AbstractDespite their economic importance and well-characterized domestication syndrome, the genomic impact of domestication and the identification of variants underlying the domestication traits in Cucurbita species (pumpkins and squashes) is currently lacking. Cucurbita argyrosperma, also known as cushaw pumpkin or silver-seed gourd, is a Mexican crop consumed primarily for its seeds rather than fruit flesh. This makes it a good model to study Cucurbita domestication, as seeds were an essential component of early Mesoamerican diet and likely the first targets of human-guided selection in pumpkins and squashes. We obtained population-level data using tunable Genotype by Sequencing libraries for 192 individuals of the wild and domesticated subspecies of C. argyrosperma across Mexico. We also assembled the first high-quality wild Cucurbita genome. Comparative genomic analyses revealed several structural variants and presence/absence of genes related to domestication. Our results indicate a monophyletic origin of this domesticated crop in the lowlands of Jalisco. We found evidence of gene flow between the domesticated and wild subspecies, which likely alleviated the effects of the domestication bottleneck. We uncovered candidate domestication genes that are involved in the regulation of growth hormones, plant defense mechanisms, seed development, and germination. The presence of shared selected alleles with the closely related species Cucurbita moschata suggests domestication-related introgression between both taxa.

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Complete chloroplast genomes of Leptodermis scabrida complex: comparative genomic analyses and phylogenetic relationships

Gene ◽

10.1016/j.gene.2021.145715 ◽

2021 ◽

pp. 145715

Author(s):

Ying Zhang ◽

Zhengfeng Wang ◽

Yanan Guo ◽

Sheng Chen ◽

Xianyi Xu ◽

...

Keyword(s):

Phylogenetic Relationships ◽

Comparative Genomic ◽

Chloroplast Genomes ◽

Genomic Analyses

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Pseudogenized Amelogenin Reveals Early Tooth Loss in True Toads (Anura: Bufonidae)

Integrative and Comparative Biology ◽

10.1093/icb/icab039 ◽

2021 ◽

Author(s):

John Shaheen ◽

Austin B Mudd ◽

Thomas G H Diekwisch ◽

John Abramyan

Keyword(s):

Tooth Loss ◽

Tooth Enamel ◽

Synonymous Substitution ◽

Bufo Bufo ◽

Molecular Dating ◽

Bufo Gargarizans ◽

The Family ◽

Synonymous Substitution Rates ◽

Mandibular Teeth ◽

Early Tooth Loss

Abstract Extant anurans (frogs and toads) exhibit reduced dentition, ranging from a lack of mandibular teeth to complete edentulation, as observed in the true toads of the family Bufonidae. The evolutionary timeline of these reductions remains vague due to a poor fossil record. Previous studies have demonstrated an association between the lack of teeth in edentulous vertebrates and the pseudogenization of the major tooth enamel gene amelogenin (AMEL) through accumulation of deleterious mutations and the disruption of its coding sequence. In the present study we have harnessed the pseudogenization of AMEL as a molecular dating tool to correlate loss of dentition with genomic mutation patterns during the rise of the family Bufonidae. Specifically, we have utilized AMEL pseudogenes in three members of the family as a tool to estimate the putative date of edentulation in true toads. Comparison of AMEL sequences from Rhinella marina, Bufo gargarizans and Bufo bufo, with nine extant, dentulous frogs, revealed mutations confirming AMEL inactivation in Bufonidae. AMEL pseudogenes in modern bufonids also exhibited remarkably high 86–93% sequence identity among each other, with only a slight increase in substitution rate and relaxation of selective pressure, in comparison to functional copies in other anurans. Moreover, using selection intensity estimates and synonymous substitution rates, analysis of functional and pseudogenized AMEL resulted in an estimated inactivation window of 46-60 MYA in the lineage leading to modern true toads, a timeline that coincides with the rise of the family Bufonidae.

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Evidence from comparative genomic analyses indicating that Lactobacillus-mediated irritable bowel syndrome alleviation is mediated by the conjugated linoleic acid synthesis

Food & Function ◽

10.1039/d0fo02616f ◽

2021 ◽

Author(s):

Yang Liu ◽

Wei Xiao ◽

Leilei Yu ◽

Fengwei Tian ◽

Gang Wang ◽

...

Keyword(s):

Irritable Bowel Syndrome ◽

Linoleic Acid ◽

Gut Microbiota ◽

Acid Synthesis ◽

Comparative Genomic ◽

Low Grade ◽

Genomic Analyses ◽

Irritable Bowel ◽

Low Grade Inflammation ◽

Gut Microbiota Dysbiosis

Irritable bowel syndrome (IBS) is a chronic intestinal disorder accompanied by low-grade inflammation, visceral hypersensitivity, and gut microbiota dysbiosis. Several studies have indicated that Lactobacillus supplementation can help to alleviate...

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