Evolution: are the monkeys' typewriters rigged?

Evolution is presumed to proceed by random mutations, which increase an individual's fitness. Increased fitness produces a higher survival rate for those individuals within populations and drives the variants to fixation over large timescales to produce new species. We recently identified positively selected sites in mitochondrial complex I in numerous, diverse taxa. In one taxon, a simple sequence repeat (SSR) encompassed the positively selected sites. We hypothesized a model in which: (i) slip-strand mis-pairing during replication due to the SSR increases the mutation rate at these sites, and (ii) a functional constraint at the protein level maintains the SSR and therefore a higher mutation rate at this site over large time scales to drive evolution. We tested this model by identifying SSRs in a mitochondrial-encoded protein in species from our previous work and determined that nearly all of the positively selected sites encompass an SSR. Furthermore, we show that our proposed model accounts for most of the mutations at neutral sites but it is probably the predominant mechanism at positively selected sites. This suggests that evolution does not proceed by simple random processes but is guided by physical properties of the DNA itself and functional constraint of the proteins encoded by the DNA.