Evolution in small steps - A nearly-universal rule of negative selection on codons

The widely accepted view that evolution proceeds in small steps is based on two assumptions: i) negative selection acts strongly against large differences (Kimura 1983); and ii) positive selection favors small-step changes (Fisher 1930). The two assumptions are not biologically connected and should be evaluated separately. To do so, we measure the substitution rates between codons, using the physico-chemical distance between amino acids (AAs) for step size. The distance used is a function of 48 physico-chemical properties. Between 9 pairs of closely-related species of plants, invertebrates and vertebrates, the evolutionary rate is indeed strongly and negatively correlated with the AA distance (ΔU, scaled to [0, 1]). Remarkably, ΔU is strongly correlated with the evolutionary rate (R2 u003e 0.8) in almost all taxa, as long as the genes are under some negative selection. ΔU is thus a nearly-universal measure of evolutionary constraint. We conclude that negative selection is the driving force of the small-step evolution, the strength of which is governed by ΔU. The possibility that positive selection may not follow the small-step rule will be tested in the companion study.