Agreed, which I why I spent time detailing how conservation is explained by natural selection having driven some sequence to a local optimum, and why the evolutionary sampling of sequence space is extremely biased, and why the number of sequences sampled for even a relatively short protein is only an infinitesimal fraction of that total space.
- On what a local optimum is in the fitness landscape analogy.
- On how the sampling of sequence space around a particular protein is highly biased.
- On how only a tiny fraction of the total space is sampled.
And as we saw above, handwaves in the direction of “statistics of sample size”, or the ruggedness of the fitness landscape, do not constitute meaningful rebuttals to these issues either.