Once they found what genes were all about the Darwinians thought they had a mechanism to support the entire thesis in every detail ~ to wit: mutations in genes, occuring for a variety of reasons, with "beneficial" genes assisting in adaptation.
Subsequent research has demonstrated that virtually all "mutations" at the base-pair level do nothing ~ this is because (according to some sources) because every protein produced in a gene is readily assembled by at least three different ways ~ so most variations don't create changes in the intended product.
Genetic change other than mutation, e.g. duplication, (deletion), and reordering have far greater impact, and do so at far faster rates.
DNA methylation has recently come under indepth study and that process might well account for far more change than we can yet imagine.
Evolution follows few of the possible paths to antibiotic resistance
Mutations may not be as helpful for neo-Darwinian evolution as expected.