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This is a good paper with an empirical example of a molecule level ratchet effect, but the message here is way overstated. It is definitely NOT the case that evolution "can't go in reverse" as a categorical statement.

1) First and most importantly, if selection pressure was reversed in sexually reproducing species, it is (a) unlikely that the ancestral allele will ever completely die out and (b) also unlikely that a sequence of recombinational events could not reconstruct the ancestral allele.

So reversed selection pressure would lead to an increase in frequency of the ancestral allele. Doesn't require the (much higher) level of difficulty of pushing six consecutive mutations to fixation in a single protein.

In bacteria or archaea it would be even easier -- just pick up the ancestral allele through horizontal gene transfer.

2) Second, even discounting sexual reproduction for now, given strong enough reversed selection pressure, either the species would go extinct or (more likely) some other protein would have been co-opted into pursuing the new function. That is, this road might be blocked but another one will almost certainly be open.

3) Third, this particular example has an accumulation of several mutations that act as blockades in fitness space. But this is far from generally proven. You'd need to do some serious correlation of activity with multiple sequence/structure alignments across large families of proteins to show this ratchet effect.

4) Finally, the whole concept of QSAR (quantitative structure activity relationships) is based on the idea that activity-structure relationships tend to be more continuous than not, in the sense that small changes usually have small effects on activity [though in dealing with adding atoms to molecules, you're talking about irreducibly large step sizes in different dimensions]).

And continuous alterations in activity usually imply reversibility as a function of many small steps.



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