I think using an alphabet of length 4 is probably a specialized enough use case that it deserves its own analysis from whole cloth if your goal is maximal performance.

I work on text search where the alphabet size is 256. If someone told me to work on text search where the alphabet size is 4, a lot of what I'd do would change, starting with my benchmark inputs.

So I kind of think responding to general claims about substring performance with, "well in DNA searching..." is kind of reframing the discussion to a specialized use case with very different priors. That is, I'm not sure anyone ever said running BM on DNA was a good idea. But maybe it's convenient, so that's what folks do. :-)