Figure 2.

Candidate somatic mutations are highly enriched for true somatic mutations. (A–C) The transition–transversion (Ti:Tv) ratio, nonsynonymous–synonymous (N:S) ratio, and four-way PhastCons score at missense substitution sites for CTVT somatic variants were statistically significant outliers (two-sided Grubb's test, critical value of Z for 188 observations = 3.59) compared to both the canid WGS panel and the CTVT founder's inherited alleles. (D–F) Substitution profiles in their trinucleotide sequence context for germline variation averaged across the 186 canids (D), the CTVT founder's putative inherited alleles (E), and the candidate CTVT somatic mutations (F). Germline variants have more C>T and T>C variants than other substitutions, but no dramatic overrepresentation of surrounding sequence contexts. In contrast, the CTVT candidate somatic mutations are enriched for C>T transitions, especially TCC>TTC (15.9%) and CCC>CTC (6.0%). Notably, the enrichment of T>C substitutions is also absent from the CTVT candidate somatic mutations. For all three plots, the base substitutions are indicated by color and displayed relative to the reference pyrimidine base (i.e., C>A and G>T transversions are shown together). Each bar conveys the fraction of variants for which the indicated substitution occurs in the context of the adjacent bases in the reference sequence. For example, the leftmost bar represents the percentage of mutations that are ACA>AAA transversions.