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Basic Characteristics of Mutations
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Mutation Site
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E484K |
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Mutation Site Sentence
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Encouragingly, c/µ+Ka/Ks identified 32 top nonsynonymous mutations (in order of decreasing c/μ: D614G, P681H, N501Y, D1118H, T716I, A570D, S982A, L452R, T478K, D950N, T19R, E484K, K417N, L18F, G142D, V1176F, D138Y, T1027I, T95I, T20N, P26S, H655Y, A701V, R190S, D80A, D215G, A222V, S477N, F490S, N439K, R346K, and K440K) (Table 3, Fig. 3) and are all located within the S1 region (N-terminal domain/NTD and Receptor-binding domain/RBD) and S2 region (including Heptad-Repeat 1/HR1 and Heptad-Repeat 2/HR2). |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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S |
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Standardized Encoding Gene
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S
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Genotype/Subtype
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- |
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Viral Reference
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Wuhan-Hu-1
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Functional Impact and Mechanisms
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Disease
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-
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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39584063
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Title
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Enhanced detection and molecular modeling of adaptive mutations in SARS-CoV-2 coding and non-coding regions using the c/micro test
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Author
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Paradis NJ,Wu C
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Journal
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Virus evolution
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Journal Info
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2024 Nov 6;10(1):veae089
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Abstract
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Accurately identifying mutations under beneficial selection in viral genomes is crucial for understanding their molecular evolution and pathogenicity. Traditional methods like the Ka/Ks test, which assesses non-synonymous (Ka) versus synonymous (Ks) substitution rates, assume that synonymous substitutions at synonymous sites are neutral and thus is equal to the mutation rate (micro). Yet, evidence suggests that synonymous sites in translated regions (TRs) and untranslated regions (UTRs) can be under strong beneficial selection (Ks > micro) and strongly conserved (Ks approximately 0), leading to false predictions of adaptive mutations from codon-by-codon Ka/Ks analysis. Our previous work used a relative substitution rate test (c/micro, c: substitution rate in UTR/TR, and micro: mutation rate) to identify adaptive mutations in SARS-CoV-2 genome without the neutrality assumption of the synonymous sites. This study refines the c/micro test by optimizing micro value, leading to a smaller set of nucleotide and amino acid sites under beneficial selection in both UTR (11 sites with c/micro > 3) and TR (69 nonsynonymous sites: c/micro > 3 and Ka/Ks > 2.5; 107 synonymous sites: Ks/micro > 3). Encouragingly, the top two mutations in UTR and 70% of the top nonsynonymous mutations in TR had reported or predicted effects in the literature. Molecular modeling of top adaptive mutations for some critical proteins (S, NSP11, and NSP5) was carried out to elucidate the possible molecular mechanism of their adaptivity.
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Sequence Data
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-
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