Molecular Evolutionary Analyses of the RNA-Dependent RNA Polymerase (RdRp) Region and VP1 Gene in Human Norovirus Genotypes GII.P6-GII.6 and GII.P7-GII.6
Abstract
:1. Introduction
2. Materials and Methods
2.1. Strains Used in This Study
2.2. Time-Scaled Phylogenetic Analyses
2.3. Phylogenetic Distance Analyses
2.4. Phylodynamic Analyses
2.5. Selective Pressure Analyses
2.6. Construction of the 3D Structure of RdRp and VP1 Proteins
2.7. Conformational B-Cell Epitope Prediction
3. Results
3.1. Time-Scaled Phylogeny of the RdRp Region and VP1 Gene in HuNoV GII.P6-GII.6 and GII.P7-GII.6
3.2. Evolutionary Rates of the RdRp Region and VP1 Gene in HuNoV GII.P6-GII.6 and GII.P7-GII.6
Region/Gene | Evolutionary Rates (95% HPDs) (Substitutions/Site/Year) | Compared Groups and Statistical Values |
---|---|---|
All RdRp region (141 strains) P6-type 15 strains; P7-type 126 strains | 3.287 × 10−3 (2.489 × 10−3–4.098 × 10−3) | All RdRp region vs. All GII.6 VP1 gene p < 0.001 |
All GII.6 VP1 gene (141 strains) P6-type 15 strains; P7-type 126 strains | 3.345 × 10−3 (2.295 × 10−3–4.419 × 10−3) | |
P6-type RdRp region (15 strains) | 5.063 × 10−3 (3.525 × 10−3–6.595 × 10−3) | P6-type RdRp region vs. P7-type RdRp region p < 0.001 |
P7-type RdRp region (126 strains) | 3.022 × 10−3 (2.268 × 10−3–3.775 × 10−3) | |
GII.P6-GII.6 VP1 gene (15 strains) | 3.725 × 10−3 (1.843 × 10−3–5.549 × 10−3) | GII.P6-GII.6 VP1 gene vs. GII. P7-GII.6 VP1 gene p < 0.001 |
GII.P7-GII.6 VP1 gene (126 strains) | 3.482 × 10−3 (2.419 × 10−3–4.568 × 10−3) |
3.3. Phylogenetic Distances among the Present Strains
3.4. Phylodynamics of GII.P6-GII.6 and GII.P7-GII.6
3.5. Positive Selection Sites in the RdRp and VP1 Proteins
3.6. Negative Selection Sites in RdRp and VP1 Proteins
3.7. 3D Mapping Relationships between Amino Acid Substitutions and Active Sites of the RdRp Dimer Proteins
3.8. 3D Mapping of the Positive Selection Sites and Conformational Epitopes in the VP1 Trimer Proteins
Region/Gene | Number of Negative Selection Sites | Number of Positive Selection Sites | Estimated as Positive Selective Sites |
---|---|---|---|
P6 type and P7 type RdRp region | 258 | 0 | — |
P6 type RdRp region | 3 | 0 | — |
P7 type RdRp region | 205 | 1 | 126Lys, Lys126Arg |
GII.P6-GII.6 and GII.P7-GII.6 VP1 gene | 298 | 2 | 354Pro, 390Asn |
GII.P6-GII.6 VP1 gene | 8 | 1 | Lys386His |
GII.P7-GII.6 VP1 gene | 274 | 2 | Pro354Thr, Ser and Gln, Asn390Thr and Asp |
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Region/Gene | Phylogenetic Distance (Mean ± SD) | Phylogenetic Distance (Median [IQR]) |
---|---|---|
All RdRp region (141 strains) | 0.112 ± 0.098 | 0.082 (0.028–0.172) |
All GII.6 VP1 gene (141 strains) | 0.317 ± 0.259 | 0.437 (0.031–0.530) |
P6-type RdRp region (15 strains) | 0.018 ± 0.017 | 0.021 (0.001–0.029) |
P7-type RdRp region (126 strains) | 0.078 ± 0.064 | 0.057 (0.023–0.130) |
GII.P6-GII.6 VP1 gene (15 strains) | 0.021 ± 0.019 | 0.027 (0.001–0.035) |
GII.P7-GII.6 VP1 gene (126 strains) | 0.305 ± 0.249 | 0.408 (0.024–0.535) |
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Takahashi, T.; Kimura, R.; Shirai, T.; Sada, M.; Sugai, T.; Murakami, K.; Harada, K.; Ito, K.; Matsushima, Y.; Mizukoshi, F.; et al. Molecular Evolutionary Analyses of the RNA-Dependent RNA Polymerase (RdRp) Region and VP1 Gene in Human Norovirus Genotypes GII.P6-GII.6 and GII.P7-GII.6. Viruses 2023, 15, 1497. https://doi.org/10.3390/v15071497
Takahashi T, Kimura R, Shirai T, Sada M, Sugai T, Murakami K, Harada K, Ito K, Matsushima Y, Mizukoshi F, et al. Molecular Evolutionary Analyses of the RNA-Dependent RNA Polymerase (RdRp) Region and VP1 Gene in Human Norovirus Genotypes GII.P6-GII.6 and GII.P7-GII.6. Viruses. 2023; 15(7):1497. https://doi.org/10.3390/v15071497
Chicago/Turabian StyleTakahashi, Tomoko, Ryusuke Kimura, Tatsuya Shirai, Mitsuru Sada, Toshiyuki Sugai, Kosuke Murakami, Kazuhiko Harada, Kazuto Ito, Yuki Matsushima, Fuminori Mizukoshi, and et al. 2023. "Molecular Evolutionary Analyses of the RNA-Dependent RNA Polymerase (RdRp) Region and VP1 Gene in Human Norovirus Genotypes GII.P6-GII.6 and GII.P7-GII.6" Viruses 15, no. 7: 1497. https://doi.org/10.3390/v15071497