Research on accurately modeling rates of mutation has been conducted for many years. A recent paper by Ziheng Yang and Rasmus Nielsen compared various methods and developed a new modeling method. They found that the new method was preferable for its smaller biases, which make it useful for large scale screening, but that the maximum-likelihood model was preferable in most scenarios because of its simplicity, and its flexibility in comparing multiple sequences while taking into account phylogeny.
Further research by Yang and Nielsen found that nonsynonymous to synonymous substitution ratios varied across loci in differing evolutionary lineages. During their study of nuclear loci of primates, even-toed ungulates, and rodents, they found that the ratio varied significantly at 22 of the 48 loci studied. This result provides strong evidence against a strictly neutral theory of molecular evolution, which states that mutations are mostly neutral or deleterious, and provides support for theories that include advantageous mutations.