Is the Mutation Rate Lower in Genomic Regions of Stronger Selective Constraints?

A study of the plant Arabidopsis thaliana detected lower mutation rates in genomic regions where mutations are more likely to be deleterious, challenging the principle that mutagenesis is blind to its consequence. To examine the generality of this finding, we analyze large mutational data from baker's yeast and humans. The yeast data do not exhibit this trend, whereas the human data show an opposite trend that disappears upon the control of potential confounders. We find that the Arabidopsis study identified substantially more mutations than reported in the original data-generating studies and expected from Arabidopsis' mutation rate. These extra mutations are enriched in polynucleotide tracts and have relatively low sequencing qualities so are likely sequencing errors. Furthermore, the polynucleotide "mutations" can produce the purported mutational trend in Arabidopsis. Together, our results do not support lower mutagenesis of genomic regions of stronger selective constraints in the plant, fungal, and animal models examined.