Figure 1

The procedure used for random sampling of mutations at non-synonymous sites in the NSMC test. Step 1 includes the selection of a sample of non-synonymous sites such that the number of sites and their base composition were the same as in the entire set of synonymous substitutions in the given gene; sampling was performed without replacement. The comparison of the number of hotspots, i.e., sites with at least two substitutions, between the samples of synonymous and non-synonymous sites gives a measure of the skewness of the distribution of mutations (Step 2). Synonymous sites and sampled non-synonymous sites are shown by inverse shading, synonymous hotspots are shown in yellow, and simulated non-synonymous hotspots are shown in green.