Phylogenomics and population genomics of sars-cov-2 in mexico during the pre-vaccination stage reveals variants of interest b.1.1.28.4 and b.1.1.222 or b.1.1.519 and the nucleocapsid mutation s194l associated with symptoms
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Understanding the evolution of the SARS-CoV-2 virus in various regions of the world during the Covid-19 pandemic is essen-tial to help mitigate the effects of this devastating disease. We describe the phylogenomic and population genetic patterns of the virus in Mexico during the pre-vaccination stage, including asymptomatic carriers. A real-time quantitative PCR screening and phylogenomic reconstructions directed at sequence/structure analysis of the spike glycoprotein revealed mutation of concern E484K in genomes from central Mexico, in addition to the nationwide prevalence of the imported variant 20C/S:452R (B.1.427/9). Overall, the detected variants in Mexico show spike protein mutations in the N-terminal domain (i.e. R190M), in the receptor-binding motif (i.e. T478K, E484K), within the S1–S2 subdomains (i.e. P681R/H, T732A), and at the basis of the protein, V1176F, raising concerns about the lack of phenotypic and clinical data available for the variants of interest we postulate: 20B/478K.V1 (B.1.1.222 or B.1.1.519) and 20B/P.4 (B.1.1.28.4). Moreover, the population patterns of single nucleotide variants from symptomatic and asymptomatic carriers obtained with a self-sampling scheme confirmed the presence of several fixed variants, and differences in allelic frequencies among localities. We identified the mutation N:S194L of the nucleocapsid protein associated with symptomatic patients. Phylogenetically, this mutation is frequent in Mexican sub-clades. Our results highlight the dual and complementary role of spike and nucleocapsid proteins in adaptive evolution of SARS-CoV-2 to their hosts and provide a baseline for specific follow-up of mutations of concern during the vaccination stage. © 2021 The Authors.
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Asymptomatic; Mexico; Nucleocapsid; Population genomics; SARS-CoV-2; Variants virus spike protein; nucleocapsid phosphoprotein, SARS-CoV-2; phosphoprotein; allele; amino acid substitution; amino terminal sequence; Article; asymptomatic carrier; bioinformatics; cladistics; controlled study; follow up; gene frequency; gene identification; gene mutation; genetic analysis; genetic association; genotyping technique; glycosylation; haplotype; human; major clinical study; minimum inhibitory concentration; phylogenomics; phylogeny; phylogeography; population genomics; prevalence; real time reverse transcription polymerase chain reaction; receptor binding; SARS-CoV-2 variant B.1.1.222; SARS-CoV-2 variant B.1.1.28.4; SARS-CoV-2 variant B.1.1.519; sequence alignment; sequence analysis; Severe acute respiratory syndrome coronavirus 2; single nucleotide polymorphism; three dimensional printing; vaccination; variant of interest; virus load; virus nucleocapsid; administration and dosage; classification; epidemiology; genetics; heterozygote; immunology; isolation and purification; Mexico; mutation; phylogeny; prevention and control; vaccination; virology; virus genome; Carrier State; Coronavirus Nucleocapsid Proteins; COVID-19; COVID-19 Vaccines; Genome, Viral; Humans; Mexico; Mutation; Phosphoproteins; Phylogeny; SARS-CoV-2; Vaccination
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