Fig. 2. New CH gene-specific mutation landscapes and fitness effects.

a, Location and type of mutation across the gene body for new drivers of CH. Filled black circles, missense mutations; filled white circles, truncating mutations (frameshift indel or nonsense mutations). b, Twenty-five recurrently mutated sites with the highest estimated fitness effects include several mutations in new CH driver genes. The error bars for the inferred fitness effect and mutation rate parameters are the CI. The number of observations of VAF for each mutation used to infer parameters is presented in Supplementary Table 4. c, Ten recurrently mutated sites with the highest estimated mutation rate. Of note, MYD88 Leu273Pro, which lies outside the SANT domain, has one of the highest mutation rates within the dataset but did not have a significantly increased fitness effect. The error bars for the inferred fitness effect and mutation rate parameters are the CI. The number of observations of VAF for each mutation used to infer parameters is presented in Supplementary Table 4. d, Fitness estimates for MTA2 plotted across the gene body, which primarily localize to the SANT domain. The error bars for the inferred fitness effect and mutation rate parameters are the CI. The number of observations of VAF for each mutation used to infer parameters is presented in Supplementary Table 4. Amino acid positions are colored by the gene elements shown in the key. Orange shading refers to new fitness-inferred genes of CH; classical fitness-inferred genes of CH are shown in blue, and classical non-fitness-inferred CH genes are shown in green.