Δ-dN/dS: New Criteria to Distinguish among Different Selection Modes in Gene Evolution

One of the most widely-used measures for protein evolution is the ratio of nonsynonymous distance (dN) to synonymous distance (dS). Under the assumption that synonymous substitutions in the coding region are selectively neutral, the dN/dS ratio can be used to test the adaptive evolution if dN/dS>1 statistically significantly. However, due to selective constraints imposed on amino acid sites, most encoding genes demonstrate dN/dS1-H for the adaptive evolution. The potential of this new method for resolving the neutral-adaptive debates has been illustrated by case studies. For over 4000 vertebrate genes, virtually all of them showed dN/dS1 (strong positive selection) or 1-H<CN/CS<1 (weak positive selection, combined with strong purifying selection), whereas nearly neutral selection due to reduced effective clonal size is highly unlikely in cancer evolution.