Fig. 2: Unique mutational signature found in somatic mutations dates cancer to >200 years old.
a, Trinucleotide context of SNVs found in healthy clams (top) and high-confidence somatic mutations in PEI (middle) or USA (bottom) sub-lineages, corrected for mutational opportunities in the clam genome. The trinucleotide order is the same as in b. b, De novo extracted mutational biases for SigS. c,d, Sig5′ (c) and SigS (d) attributed mutations per Mb (signature fitting estimates with fitting error) across USA MarBTN samples (n = 5) by sampling date. Results of linear regression with 95% CI (gray) overlaid. SNVs found in healthy clams, PEI MarBTN samples or LOH regions are excluded. e, Fraction of SNVs attributed to SigS from healthy clams (black), variants found in all MarBTN samples (gray) and high-confidence somatic mutations (colored). Variants found in all MarBTN samples are divided by whether they are found in healthy clams and whether they are homozygous (hmz) or heterozygous (htz). Dashed lines display SigS fraction estimates for likely somatic mutations and likely founder variants. f, Age estimate of the most recent common ancestor (MRCA) of the USA and PEI sub-lineages using Sig5′ and SigS and of the BTN origin from SigS mutations. g, dN:dS ratios (ratio of 1 indicates neutrality) for SNVs found in healthy clams (black), SNVs found in all MarBTN samples (gray) and high-confidence somatic mutations (colored) (n = 20,075,227, 7,676,209, 2,596,657, 320,715, 331,167 and 651,882 as shown from left to right). Error bars in all plots display 95% CI.
