Extended Data Figure 1: The effect of recurrence across different mutation and functional classes.

a, TiTv (transition to transversion) ratio of synonymous variants at downsampled intervals of ExAC. The TiTv is relatively stable at previous sample sizes (<5,000), but changes drastically at larger sample sizes. b, For synonymous doubleton variants, mutability of each trinucleotide context is correlated with mean Euclidean distance of individuals that share the doubleton. Transversion (red), and non-CpG transition (green) doubletons are more likely to be found in closer PCA space (more similar ancestries) than CpG transitions (blue). c, The proportion singleton among various functional categories. The functional category stop lost has a higher singleton rate than nonsense. Error bars represent standard error of the mean. d, Among synonymous variants, mutability of each trinucleotide context is correlated with proportion singleton, suggesting CpG transitions (blue) are more likely to have multiple independent origins driving their allele frequency up. e, The proportion singleton metric from c, broken down by transversions, non-CpG transitions, and CpG variants. Notably, there is a wide variation in singleton rates among mutational contexts in functional classes, and there are no stop-lost (variants that result in the loss of a stop codon) CpG transitions. Error bars represent standard error of the mean.