Hi @swamidass and @Rumraket,
Thanks very much for your kind responses. After reading @Rumraket’s takedown, it appears to me that Dr. Miller (who is a physicist, not a biochemist) has failed to understand the role of purifying selection.
Yeah, that’s what happens in the absence of purifying selection. If deleterious mutations aren’t weeded out, they invariably accumulate. If no compensatory effects are allowed, fitness will decline. This is a surprise to exactly no evolutionary biologist ever.
In another comment in response to Dr. Miller, @Rumraket adds:
The other paper you cited (Lundin et al 2018) explored the fitness effects of mutations and found, completely unsurprisingly that most mutations are deleterious. They didn’t find anything which supports the view that protein evolution can only go downhill as mutations accumulate. Their protocol did not even include a lineage evolving under purifying selection. All mutations were created directly in DNA by PCR and then inserted in the bacterial chromosome and their fitness effects were tested. When the effects of multiple mutations in combination were tested, it was again the in absence of purifying selection.
I was also interested to read @Mercer’s remark over on the other post:
If one wishes to estimate how hard it is for evolution to find new functions in sequence space, mutating an existing wild-type protein makes little sense–but Axe didn’t even do that. He mutated a [temperature-sensitive mutant] protein that had already been selected to be on the edge of stability.
The conclusion that this was done to generate the lowest number is hard to escape.
All in all, not such a convincing paper, after all. @swamidass sums it up well:
The best thing to do is just tune out the theatrical parts of the paper. They are always going to claim grand success, no matter what.