Figure 5

Regions surrounding SAVs are under greater non-coding evolutionary constraint. (a) We created a 192-codon position-specific scoring matrix based on genome-wide conservation levels across mammals. Matrix scores are visualized increasing from green to red. As scores are inversely proportional to the genome-wide conservation of each codon position, conservation levels can also be visualized using the same matrix, decreasing from green to red. (b) For each variant, four-way mammalian multiple DNA alignments were extracted for a region surrounding the variant, and a score assigned to each fully conserved column via the scoring matrix, and the total normalized by the length of the alignment. An example of a random synonymous CγG variant is shown. (c) The mean conservation score for all SAVs (blue arrow) and SAVs on autosomes (yellow arrow) was compared to a distribution of randomly sampled sets of scores from all hSNPs (orange distribution). Randomly sampled distributions of hSNPs were also created controlling for minimum distance from a splice junction by having similar distributions in this regard as SAVs (blue distribution). A distribution of mean conservation scores was also produced for hSNPs from autosomes also controlled by minimum distance from the splice site (yellow distribution).