Fig. 3: Clonal selection and competition differ according to country.
From: Somatic mutations in facial skin from countries of contrasting skin cancer risk
a, Number of mutations of each consequence for positively selected genes (dNdScv: q < 0.01) according to country. ARID2 is not significantly positively selected in the Singapore samples. b, Plot of non-synonymous mutations per gene in Singapore versus UK samples. Gradient of line: total number of non-synonymous mutations in the UK/Singapore = 6,846/1,432. Positively selected genes (purple) are labeled. Red indicates positively selected genes with a significant (one-sided likelihood ratio test: Padj < 0.001) difference in dN/dS ratio according to country, after accounting for global differences. c, A representation of protein-altering mutations in 1 cm2 of skin from donors from Singapore and the UK. Samples were randomly selected and mutations are displayed as circles, randomly distributed in the space. Sequencing data, including copy number, were used to infer the size and number of clones and, where possible, the nesting of subclones. Otherwise, subclones are nested randomly. d, Estimated percentage of cells with at least one non-synonymous mutation per positively selected gene, according to country (n = 11 donors, samples with known CNA removed). Tukey box plot where the lower and upper hinges represent the first and third quartile, the center represents the median and the outliers are more than 1.5× the IQR. Two-sided Wilcoxon signed-rank test: Padj = 0.03 (NOTCH1), 0.66 (NOTCH2), 8.7 × 10−3 (FAT1) and 0.05 (TP53) with Holm multiple testing correction. e, Estimated percentage of cells with at least one non-synonymous mutation across 74 genes according to country (Methods; n = 11 donors, two-sided Wilcoxon signed-rank test: P = 4.3 × 10−3). Tukey box plot where the lower and upper hinges represent the first and third quartile, the center represents the median and the outliers more than 1.5× the IQR. f, Violin plot comparing clone size distributions (summed variant allele fraction) per mutation according to country. UK donor mutations had a lower mean clone size (two-sided Welch’s t-test: P = 4.27 × 10−14).
