Young proteins experience more variable selection pressures than old proteins

Abstract

It is well known that young proteins tend to experience weaker purifying selection and evolve more quickly than old proteins. Here, we show that, in addition, young proteins tend to experience more variable selection pressures over time than old proteins. We demonstrate this pattern in three independent taxonomic groups: yeast, Drosophila, and mammals. The increased variability of selection pressures on young proteins is highly significant even after controlling for the fact that young proteins are typically shorter and experience weaker purifying selection than old proteins. The majority of our results are consistent with the hypothesis that the function of a young gene tends to change over time more readily than that of an old gene. At the same time, our results may be caused in part by young genes that serve constant functions over time, but nevertheless appear to evolve under changing selection pressures due to depletion of adaptive mutations. In either case, our results imply that the evolution of a protein-coding sequence is partly determined by its age and origin, and not only by the phenotypic properties of the encoded protein. We discuss, via specific examples, the consequences of these findings for understanding of the sources of evolutionary novelty.

Figure 1.

According to conceptual models of protein evolution, young genes experience more variable selection pressures over time than old genes. The two examples shown here illustrate a young gene that arose at the common ancestor of species 1–4 (stars), compared with an old gene that arose in the distant past. (Bottom) The cumulative number of nonsynonymous substitutions over time, the slope of which is proportional to the d_N/d_S value. If the young gene retains its original function (left), it rapidly depletes adaptive sites, resulting in a dramatic slowdown in the nonsynonymous substitution rate: ω₂ < ω₁. If the young gene experiences a functional change in a lineage (either relaxed constraint or neofunctionalization; right), as indicated by a lighting bolt, it rapidly accumulates nonsynonymous substitutions, resulting in ω₂ > ω₁. In both cases the young gene experiences variable selection pressures (i.e., large |ω₁ – ω₂|), whereas the old gene experiences roughly the same selection pressure in recent times, because it retains its function and most of its adaptive sites have already been depleted: ω₂ ≈ ω₁.

Figure 2.

The five-species phylogeny for each of the taxa analyzed in our study (yeast, mammals, Drosophila). For each ortholog we estimated branch-specific d_N/d_S values along two subsequent branches (ω₁, ω₂), as well as separate values for most terminal branches (ω₃), the outgroup branch (ω₀), and additional internal branches in Drosophila (ω₄). We quantified the temporal variability in d_N/d_S as the absolute difference ν = |ω₁ – ω₂|.

Figure 3.

The distribution of d_N/d_S values (ω₁) among old and young mammalian genes. The old genes are skewed toward lower d_N/d_S values, but there is a substantial overlap. When comparing old and young genes we control for this bias by analyzing a subset of old and young genes with the same distributions of ω₁ values.