KaKs

KaKs, often written as dN/dS, is a ratio used in molecular evolution to quantify selective pressure on protein-coding genes. Ka denotes the rate of non-synonymous substitutions (those that alter amino acids), while Ks denotes the rate of synonymous substitutions (silent changes). The ratio provides a summary of how protein-coding regions evolve under different selective regimes.

Computation and methods rely on codon-aligned coding sequences. Substitution rates are estimated per site and per codon, then combined to yield Ka and Ks. Common approaches include pairwise comparisons and codon-based models (for example, methods implemented in various phylogenetics and population-genetics software). Estimates can be reported for whole genes, regions, or sliding windows along a sequence, and site- or branch-specific analyses can test for variation in selective pressure.

Interpretation follows a general rule: Ka/Ks > 1 suggests positive selection driving amino-acid changes; Ka/Ks < 1 implies purifying (negative) selection removing deleterious amino-acid changes; Ka/Ks ≈ 1 indicates neutral evolution with little selective constraint. In practice, interpretation depends on divergence level, alignment quality, and model assumptions. Low Ks can inflate the ratio; saturation at Ks in distant comparisons and recombination can bias results.

Applications include identifying genes subject to adaptive evolution, studying functional divergence after gene duplication, and comparing selective pressures across lineages or functional categories. KaKs remains a widely used but method-sensitive tool in comparative genomics and evolutionary biology.