The specific mechanism notwithstanding, it is clear that synonymous mutations are not always neutral; however, the degree of variability in their fitness effects, and how often they contribute to adaptation, remains unknown.

What mutations are neutral?

In population genetics, mutations in which natural selection does not affect the spread of the mutation in a species are termed neutral mutations. Neutral mutations that are inheritable and not linked to any genes under selection will either be lost or will replace all other alleles of the gene.

Is synonymous substitution neutral?

They are either slightly deleterious or slightly advantageous, and mutation–selection–drift equilibrium is expected for codon usage. Thus, most synonymous substitutions are neutral in the broad sense. Average selection intensity is smaller for synonymous than for nonsynonymous substitutions.