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Fig 1.

Distribution of the 3,067 genomes used in this study by country and date of isolation.

A) The pie chart represents the percentage of genomes used in this study according to their geographic origins. The colors indicate different countries. B) Number of genomes of complete pathogens, distributed over a period of 3 months from the end of December to the end of March.

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Fig 2.

Schematic representation illustrating the distribution of recurrent non-synonymous mutations along the SARS-CoV-2 genome.

The brown and garnet diagrams illustrate the non-structural proteins (nsp1 to nsp 16) of the orf1ab protein and the two subunits of the spike protein, respectively. Recurrent mutations represented by vertical lines. The frequency of each mutation in the population is presented by color coded circles. Abbreviations: S, spike; E, enveloppe; M, membrane protein; N, nucleocapsid protein; CT, Cytoplasmic chail.

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Fig 3.

Map showing geographical distribution of recurrent mutation in the studied population worldwide.

The pie charts show the relative frequencies of haplotype for each population. The haplotypes are color coded as shown in the key. The double-digit represent countries' two letters code. The circle's size was randomly generated with no association with the number of genomes in each country. Abbreviations: S, spike; E, enveloppe; M, membrane protein; N, nucleocapsid protein.

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Fig 4.

The graph represents substitutions accumulation in a three months period.

A) The accumulation of mutations increases linearly with time. The dots represent the number of mutations in each genome. All substitutions have been included: non-synonymous, synonymous and intergenic mutations. B) The distribution and accumulation of Hot spot mutations over time.

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Fig 5.

Phylogenetic analysis of 3067 SARS-CoV 2 genomes grouped according to the country of origin.

The length of the branches represents the distance in time.

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Fig 6.

Heatmap showing the correlation between mutations and the geographic distribution of the genomes analyzed.

The correlation was applied to a data set of 68 most recurrent mutations with different distribution in all 55 countries divided into two distinct cluster A and B. The color scale indicates the significance of correlation with blue and orange colors indicating the highest and lowest correlation. The red, yellow and orange colors in the horizontal bar represent the continent of origin. Abbreviations: S, spike; M, membrane protein; N, nucleocapsid protein.

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Table 1.

Selective pressure analysis on the spike and orf1ab genes of SARS-CoV-2.

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Table 1 Expand

Fig 7.

Structural view of selective pressure in orf1ab gene.

The residue under the positive and negative selection is highlighted in blue and red respectively. The modeling of orf1ab non-structural proteins (nsp3, nsp4, nsp6, nsp12, nsp13, nsp14, and nsp16) harboring residues under pressure selection was produced using CI-TASSER. A. The nsp3 domains MAC1, Ubl1, Ubl2-PLpro, and SUD-C are color-coded in the 3D representation. The residues Ile-1426 and Ala-655 under negative selection are located respectively on 3Eco and SUD-C domains while Thr-353 residue under positive selection is shown on the MAC1 domain. Likewise, B, C, D, E, F, and G illustrating 3D representation of the nsp4, nsp6, nsp12, nsp13, nsp14 and nsp 16 proteins, respectively.

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Fig 8.

Structural view of selective pressure in spike gene.

The negatively selected site in spike protein is highlighted in red. The only amino acid residue selected negatively on the receptor-binding domain corresponds to GLN-474. The cryo-EM structure with PDB id 6VSB was used as a model for the spike gene in its prefusion conformation.

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Fig 9.

Pangenome construction of different strains belonging to the genus Betacoronavirus.

A. The Venn diagram represents the shared and unique proteins of SARS-CoV-2 compared to the 16 species of the genus Betacoronavirus. B. The pie diagram showing the core (present in all strains) and accessory proteins (not present in all strains) at the intragenomic scale of SARS-CoV-2.

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