Evolution of the GII.3[P12] Norovirus from 2010 to 2019 in Jiangsu, China

Abstract Objectives Norovirus genotype GII.3[P12] strains have been an important pathogen for sporadic gastroenteritis infection. In previous studies of GII.3[P12], the number of specimens and time span are relatively small, which is difficult to truly reflect the infection and evolution of this type of norovirus. Here we report a molecular epidemiological study of the NoVs prevalent in Jiangsu between 2010 and 2019 to investigate the evolution of the GII.3[P12] strains in China. Methods In this study 60 GII.3[P12] norovirus strains were sequenced and analyzed for evolution, recombination, and selection pressure using bioanalysis software. Results The GII.3[P12] strains were continuously detected during the study period, which showed a high constituent ratio in males, in winter and among children aged 0–11 months, respectively. A time-scaled evolutionary tree showed that both GII.P12 RdRp and GII.3 VP1 sequences were grouped into three major clusters (Cluster I–III). Most GII.3[P12] strains were mainly located in sub-cluster (SC) II of Cluster III. A SimPlot analysis identified GII.3[P12] strain to be as an ORF1-intragenic recombinant of GII.4[P12] and GII.3[P21]. The RdRp genes of the GII.3[P12] showed a higher mean substitution rate than those of all GII.P12, while the VP1 genes of the GII.3[P12] showed a lower mean substitution rate than those of all GII.3. Alignment of the GII.3 capsid sequences revealed that three HBGA binding sites of all known GII.3 strains remained conserved, while several amino acid mutations in the predicted antibody binding sites were detected. The mutation at 385 was within predicted antibody binding regions, close to host attachment factor binding sites. Positive and negative selection sites were estimated. Two common positively selected sites (sites 385 and 406) were located on the surface of the protruding domain. Moreover, an amino acid substitution (aa204) was estimated to be near the active site of the RdRp protein. Conclusions We conducted a comprehensive analysis on the epidemic and evolution of GII.3[P12] noroviruses and the results suggested that evolution was possibly driven by intergenic recombination and mutations in some key amino acid sites.

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Evolution of the GII.3[P12] Norovirus from 2010 to 2019 in Jiangsu, China

10.21203/rs.3.rs-240713/v1 ◽

2021 ◽

Author(s):

Jian-Guang Fu ◽

Jing Ai ◽

Changjun Bao ◽

Jun Zhang ◽

Qingbin Wu ◽

...

Keyword(s):

Amino Acid ◽

Binding Sites ◽

Substitution Rate ◽

Negative Selection ◽

Acid Sites ◽

Antibody Binding ◽

Time Span ◽

Mean Substitution ◽

Amino Acid Mutations ◽

Attachment Factor

Abstract Objectives: Norovirus genotype GII.3[P12] strains have been an important pathogen for sporadic gastroenteritis infection. In previous studies of GII.3[P12], the number of specimens and time span are relatively small, which is difficult to truly reflect the infection and evolution of this type of norovirus. Here we report a molecular epidemiological study of the NoVs prevalent in Jiangsu between 2010 and 2019 to investigate the evolution of the GII.3[P12] strains in China. Methods: In this study 60 GII.3[P12] norovirus strains were sequenced and analyzed for evolution, recombination, and selection pressure using bioanalysis software. Results: The GII.3[P12] strains were continuously detected during the study period, which showed a high constituent ratio in males, among children aged 0–11 months and winter. A time-scaled evolutionary tree showed that both GII.P12 RdRp and GII.3 VP1 sequences were grouped into three major clusters (Cluster I-III). Most GII.3[P12] strains were mainly located in sub-cluster (SC) II of Cluster III. A SimPlot analysis identified GII.3[P12] strain to be as an ORF1-intragenic recombinant of GII.4[P12] and GII.3[P21]. The RdRp genes of the GII.3[P12] showed a higher mean substitution rate than those of all GII.P12, while the VP1 genes of the GII.3[P12] showed a lower mean substitution rate than those of all GII.3. Alignment of the GII.3 capsid sequences revealed that three HBGA binding sites of all known GII.3 strains remained conserved, while several amino acid mutations in the predicted antibody binding sites were detected. The mutation at 385 was within predicted antibody binding regions, close to host attachment factor binding sites. Positive and negative selection sites were estimated. Two common positively selected sites (sites 385 and 406) were located on the surface of the protruding domain. Moreover, an amino acid substitution (aa204) was estimated to be near the active site of the RdRp protein. These results suggested that evolution of the GII.3[P12] noroviruses was possibly driven by intergenic recombination and mutations in some key amino acid sites. Conclusions: The GII.3[P12] recombinant strain was dominant for the GII.P12 and GII.3 noroviruses in China, which is therefore a major concern for causing gastrointestinal infection.

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Genomic diversity of SARS-CoV-2 can be accelerated by a mutation in the nsp14 gene

10.1101/2020.12.23.424231 ◽

2020 ◽

Author(s):

Kosuke Takada ◽

Mahoko Takahashi Ueda ◽

Tokiko Watanabe ◽

So Nakagawa

Keyword(s):

Amino Acid ◽

Substitution Rate ◽

Nucleotide Substitution ◽

Acid Sites ◽

Genomic Diversity ◽

Nucleotide Substitution Rate ◽

Structural Protein ◽

Wild Type ◽

Gamma Delta ◽

Evolutionarily Conserved

AbstractNucleotide substitution rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is relatively low compared to the other RNA viruses because coronaviruses including SARS-CoV-2 encode non-structural protein 14 (nsp14) that is an error-correcting exonuclease protein. In this study, to understand genome evolution of SARS-CoV-2 in the current pandemic, we examined mutations of SARS-CoV-2 nsp14 which could inhibit its error-correcting function. First, to obtain functionally important sites of nsp14, we examined 62 representative coronaviruses belonging to alpha, beta, gamma, delta, and unclassified coronaviruses. As a result, 99 out of 527 amino acid sites of nsp14 were evolutionarily conserved. We then examined nsp14 sequences obtained from 28,082 SARS-CoV-2 genomes and identified 6 amino acid changes in nsp14 mutants that were not detected in the 62 representative coronaviruses. We examined genome substitution rates of these mutants and found that an nsp14 mutant with a proline to leucine change at position 203 (P203L) showed a higher substitution rate (35.9 substitutions/year) than SARS-CoV-2 possessing wild-type nsp14 (19.8 substitutions/year). We confirmed that the substitution rate of the P203L is significantly higher than those of other variants containing mutations in structural proteins. Although the number of SARS-CoV-2 variants containing P203L mutation of nsp14 is limited (26), these mutants appeared at least 10 times independently in the current pandemic. These results indicated that the molecular function of nsp14 is important for survival of various coronaviruses including SARS-CoV-2 and that some mutations such as P203L of nsp14 inhibiting its error-correcting function are removed rapidly due to their deleterious effects.

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Sulfadoxine Resistance in Plasmodium vivax Is Associated with a Specific Amino Acid in Dihydropteroate Synthase at the Putative Sulfadoxine-Binding Site

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.48.6.2214-2222.2004 ◽

2004 ◽

Vol 48 (6) ◽

pp. 2214-2222 ◽

Cited By ~ 64

Author(s):

Michael Korsinczky ◽

Katja Fischer ◽

Nanhua Chen ◽

Joanne Baker ◽

Karl Rieckmann ◽

...

Keyword(s):

Amino Acid ◽

Binding Site ◽

Plasmodium Vivax ◽

Binding Sites ◽

Protein Sequence ◽

Three Dimensional ◽

Specific Amino Acid ◽

Dihydropteroate Synthase ◽

Contact Residues ◽

Amino Acid Mutations

ABSTRACT Sulfadoxine is predominantly used in combination with pyrimethamine, commonly known as Fansidar, for the treatment of Plasmodium falciparum. This combination is usually less effective against Plasmodium vivax, probably due to the innate refractoriness of parasites to the sulfadoxine component. To investigate this mechanism of resistance by P. vivax to sulfadoxine, we cloned and sequenced the P. vivax dhps (pvdhps) gene. The protein sequence was determined, and three-dimensional homology models of dihydropteroate synthase (DHPS) from P. vivax as well as P. falciparum were created. The docking of sulfadoxine to the two DHPS models allowed us to compare contact residues in the putative sulfadoxine-binding site in both species. The predicted sulfadoxine-binding sites between the species differ by one residue, V585 in P. vivax, equivalent to A613 in P. falciparum. V585 in P. vivax is predicted by energy minimization to cause a reduction in binding of sulfadoxine to DHPS in P. vivax compared to P. falciparum. Sequencing dhps genes from a limited set of geographically different P. vivax isolates revealed that V585 was present in all of the samples, suggesting that V585 may be responsible for innate resistance of P. vivax to sulfadoxine. Additionally, amino acid mutations were observed in some P. vivax isolates in positions known to cause resistance in P. falciparum, suggesting that, as in P. falciparum, these mutations are responsible for acquired increases in resistance of P. vivax to sulfadoxine.

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Predicting the Strength of Stacking Interactions Between Heterocycles and Aromatic Amino Acid Side Chains

10.26434/chemrxiv.7628939.v2 ◽

2019 ◽

Author(s):

Andrea N. Bootsma ◽

Analise C. Doney ◽

Steven Wheeler

Keyword(s):

Amino Acid ◽

Binding Sites ◽

Aromatic Amino Acid ◽

Aromatic Amino Acids ◽

Biologically Active ◽

Side Chains ◽

Stacking Interactions ◽

Inhibitor Binding ◽

Protein Binding Sites ◽

Amino Acid Side Chains

Despite the ubiquity of stacking interactions between heterocycles and aromatic amino acids in biological systems, our ability to predict their strength, even qualitatively, is limited. Based on rigorous ab initio data, we have devised a simple predictive model of the strength of stacking interactions between heterocycles commonly found in biologically active molecules and the amino acid side chains Phe, Tyr, and Trp. This model provides rapid predictions of the stacking ability of a given heterocycle based on readily-computed heterocycle descriptors. We show that the values of these descriptors, and therefore the strength of stacking interactions with aromatic amino acid side chains, follow simple predictable trends and can be modulated by changing the number and distribution of heteroatoms within the heterocycle. This provides a simple conceptual model for understanding stacking interactions in protein binding sites and optimizing inhibitor binding in drug design.

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Genetic Variation and Evolution of the 2019 Novel Coronavirus

Public Health Genomics ◽

10.1159/000513530 ◽

2021 ◽

pp. 1-13

Author(s):

Salvatore Dimonte ◽

Muhammed Babakir-Mina ◽

Taib Hama-Soor ◽

Salar Ali

Keyword(s):

Amino Acid ◽

Receptor Binding ◽

Rapid Evolution ◽

Single Amino Acid ◽

Angiotensin Converting Enzyme 2 ◽

New Type ◽

Amino Acid Mutations ◽

Host Infection ◽

Human Coronaviruses ◽

Novel Coronavirus

Introduction: SARS-CoV-2 is a new type of coronavirus causing a pandemic severe acute respiratory syndrome (SARS-2). Coronaviruses are very diverting genetically and mutate so often periodically. The natural selection of viral mutations may cause host infection selectivity and infectivity. Methods: This study was aimed to indicate the diversity between human and animal coronaviruses through finding the rate of mutation in each of the spike, nucleocapsid, envelope, and membrane proteins. Results: The mutation rate is abundant in all 4 structural proteins. The most number of statistically significant amino acid mutations were found in spike receptor-binding domain (RBD) which may be because it is responsible for a corresponding receptor binding in a broad range of hosts and host selectivity to infect. Among 17 previously known amino acids which are important for binding of spike to angiotensin-converting enzyme 2 (ACE2) receptor, all of them are conservative among human coronaviruses, but only 3 of them significantly are mutated in animal coronaviruses. A single amino acid aspartate-454, that causes dissociation of the RBD of the spike and ACE2, and F486 which gives the strength of binding with ACE2 remain intact in all coronaviruses. Discussion/Conclusion: Observations of this study provided evidence of the genetic diversity and rapid evolution of SARS-CoV-2 as well as other human and animal coronaviruses.

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Codon-Substitution Models for Heterogeneous Selection Pressure at Amino Acid Sites

Genetics ◽

10.1093/genetics/155.1.431 ◽

2000 ◽

Vol 155 (1) ◽

pp. 431-449 ◽

Cited By ~ 41

Author(s):

Ziheng Yang ◽

Rasmus Nielsen ◽

Nick Goldman ◽

Anne-Mette Krabbe Pedersen

Keyword(s):

Amino Acid ◽

Positive Selection ◽

Selective Pressure ◽

Acid Sites ◽

Data Sets ◽

Protein Coding ◽

Important Indicator ◽

Diversifying Selection ◽

Codon Substitution ◽

Neutral Mutations

AbstractComparison of relative fixation rates of synonymous (silent) and nonsynonymous (amino acid-altering) mutations provides a means for understanding the mechanisms of molecular sequence evolution. The nonsynonymous/synonymous rate ratio (ω = dN/dS) is an important indicator of selective pressure at the protein level, with ω = 1 meaning neutral mutations, ω < 1 purifying selection, and ω > 1 diversifying positive selection. Amino acid sites in a protein are expected to be under different selective pressures and have different underlying ω ratios. We develop models that account for heterogeneous ω ratios among amino acid sites and apply them to phylogenetic analyses of protein-coding DNA sequences. These models are useful for testing for adaptive molecular evolution and identifying amino acid sites under diversifying selection. Ten data sets of genes from nuclear, mitochondrial, and viral genomes are analyzed to estimate the distributions of ω among sites. In all data sets analyzed, the selective pressure indicated by the ω ratio is found to be highly heterogeneous among sites. Previously unsuspected Darwinian selection is detected in several genes in which the average ω ratio across sites is <1, but in which some sites are clearly under diversifying selection with ω > 1. Genes undergoing positive selection include the β-globin gene from vertebrates, mitochondrial protein-coding genes from hominoids, the hemagglutinin (HA) gene from human influenza virus A, and HIV-1 env, vif, and pol genes. Tests for the presence of positively selected sites and their subsequent identification appear quite robust to the specific distributional form assumed for ω and can be achieved using any of several models we implement. However, we encountered difficulties in estimating the precise distribution of ω among sites from real data sets.

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