[1] If a gene has lower levels of nonsynonymous than synonymous nucleotide substitution, then it can be inferred to be functional because a Ka/Ks ratio < 1 is a hallmark of sequences that are being constrained to code for proteins.
[4] This is due to the fact that nonsynonymous substitutions are subject to much higher selective pressures than synonymous mutations.
[3] He determined that if this were true, genetic drift would be a more powerful factor in molecular evolution than natural selection.
[6] The "nearly neutral" theory proposes that molecular evolution acting on nonsynonymous substitutions is driven by mutation, genetic drift, and very weak natural selection, and that it is extremely sensitive to population size.
[9] Further research by Yang and Nielsen found that nonsynonymous to synonymous substitution ratios varied across loci in differing evolutionary lineages.