I couldn’t copy from Mercer’s post, but he said he wanted me to defend this statement, I think.
So unless functional sequences are easy to find (very common), and/or are clustered together (easily reachable from one functional island to another), explaining current protein diversity without design is impossible.
I don’t see why anyone disputes it. The main critique we got on the 2011 paper was that we didn’t start from an ancestral sequence, which had enough sequence similarity to acquire the new functions easily. People made this critique because they knew that existing proteins with different functions are far apart in sequence, stabilized by epistatic interactions among amino acids, and resistant to change toward a new function. It would require too many changes ! Does Mercer think it’s easy to convert proteins from one function to another if they are far distant in sequence space?
The question to be disputed is whether they are far distant in sequence space. This may be a surprise to some, but all Doug shows is that functional folds are very rare in sequence space, not how they are arranged in sequence space. That is another question. Arguments can be made but I am not going to do that here. I have said as much is I care to about Doug’s paper.
Are our proteins in the 2011 paper proteins with shared structure far apart in sequence space? They certainly can be. Even proteins with the same function can be, because they have differing stabilization—different epistatic interactions to stabilize the fold. Every biologist knows this instinctively. No one was surprised when we couldn’t do a conversion. So then, let us ask the key question. If proteins are so established in their particular functions that they can’t shift function easily, where did all the diversity of proteins function we have come from.? Some kind of changes are possible. I have been discussing that here with Mercer. Others do not seem to be possible, yet we see evidence they must have happened in the protein record. I simply want to point out that the conclusion that they evolved from each other is not based in any experiment. It is derived from evolutionary thinking. It may be true. Perhaps with the simpler enzymes it could be demonstrated. But the experiment must be done rather than simply assume that the patterns we see are due to evolution. Simple point. Should be understandable.
My statement above was “if this, then that”. “This” may or may not be true, so “this” is what we need to establish—if this is true.
BTW, I don’t think anyone has demonstrated that it is possible to go from a hypothetical ancestral sequence to the modern form, all the way. They have shown the first few steps and that is all.