REC
Posts: 638 Joined: Sep. 2006
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Wow....2nd 2015 publication from BioComplexity, and it is a doozy:
Axe and Gauger "tested these proposals by observing how the endpoint of simple evolutionary optimization depends on the starting point. Beginning with optimization of protein-like constructs in the Stylus computational model, we compared promiscuous and junk starting points, where design elements specific to the test function were completely absent, to a starting point that retained most elements of a good design (mutation having disrupted some). In all three cases, evolutionary optimization improved activities by a large factor."
Another round of Axe and Gauger running experiments designed to fail, therefore design (except again, some worked, but you know, still design. Not evolution. Nope. Not ever).
Oopsy.
Much handwaving BS follows. Mostly that good 'designs' (defined by them as starting points closer to their target) perform better in a few rounds of directed evolution than more distant starting points, which they call promiscuous or junk (which are totes not-designed, cuz please they be evolutionary random 'junk'). Duh.
My favorite junky 'non-design' is a totally deranged protein* with a huge deletion which apparently fails to achieve full activity in a couple rounds of kit mutagenesis. This kit in my hands only changes a few bases per clone. No insertions more than a base. They don't try shuffling to mimic recombination. Shockingly, it didn't work!! But nearer starting points (again, called designs) do, therefore design and Jesus and all that.
*Their words: "In addition to the 36 residues that are missing in the deletion mutant, another 29 residues are unequivocally prevented from adopting the wild-type conformation because of the missing segment, meaning that the structural disruption extends to 65 residues. Because this is the minimum extent of impact to the whole structure, the images on the right show the maximum amount of wild-type structure that could remain in TEMΔ. What actually remains may be much less. In addition to the deletion, TEMΔ carries 32 amino acid substitutions (see Supplement S1 [28])"
When you read that, remember that TEM is ~280 amino acids.
eta: I'm actually most bothered by their misrepresentation of some very fine science.
eta 2: I wonder what the DI and UD say about this paper. Wonder if even they are a bit ashamed.
Edited by REC on Dec. 29 2015,22:55
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