Left: dN/dS is the normalized ratio of nonsynonymous to synonymous mutations. dN represents the rate of nonsynonymous mutations per nonsynonymous site, and dS represents the rate of synonymous mutations per synonymous site. A dN/dS of ~1 is expected under neutrality. Genes with a dN/dS ratio >1, taking into account a trinucleotide-specific mutation rate, indicates the gene is under positive selection ('fitness inferred', FI). HSCs with a mutation under positive selection will clonally expand to result in CH. Right: global positive selection in blood detectable at missense, essential splice site and truncating mutations (comprising nonsense substitutions and frameshift insertions/deletions). Nonsynonymous mutations comprise missense and nonsense single base substitutions. The error bars represent the 95% CI of the dN/dS parameter for that mutation type. N = 52,701 mutations.
