There are a number of professional science journal ranking services which calculate the impact factor of each publication.
To my knowledge none of them recognize Bio-Complexity, just like they don’t recognize Creation Research Society Quarterly.
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No it doesn’t.
With respect to her first point, the extreme distance of their relationship makes the interconversion of them all the more absurd, since even if one were to do ancestor reconstruction at such an extreme age, chances are it is actually impossible to correctly infer the ancestral state for many sites, because the probability of saturation increases as the proteins become more diverged.
With respect to her second point, no, there is no reason to think such an inter-conversion actually took place unless you can actually resurrect the ancestor and show that it was in fact active primarily on one of the extant substrates.
But it is known that many enzymes actually evolved from promiscuous ancestors, being capable of catalyzing the reaction on both substrates used from either of it’s descendants.
If they really wanted to assess the feasibility of conversions within this superfamily of proteins, they’d use ancestor reconstructions for more recent nodes, and then use mutation and selection screening of mutants to test for functions.
Ironically the hypothesis they are testing is whether it is possible to convert one enzyme directly into another by rational design, using some knowledge of how the enzymes functions and relies on particular residues to perform that function. The irony is that, using this method, it fails.
So the ID method failed, and they didn’t even test the evolutionary scenario, they test one they made up. And it is very very very difficult not speculate that they made up a straw man of an evolutionary scenario by stacking the deck against it as much as possible. Why else use such distantly related proteins?
They could have picked proteins that are 70% to 80% similar instead, used a broader “taxon” sample, inferred ancestral states, and THEN tested the “convertibility” of this ancestor. THAT would have been an actual test of what modern evolutionary theory says actually happened.
With respect to her last point that it is somehow implied there are only few or narrow sets of pathways for protein evolution to follow. If that is the case, so what? Then it is possible and evolution can follow them.
It should be noted, though, that for proteins where it has even been attempted to elucidate how many pathways there are between the ancestors and there descendants, there are hundreds:
Starr TN, Picton LK, Thornton JW. Alternative evolutionary histories in the
sequence space of an ancient protein. Nature. 2017 Sep 21;549(7672):409-413. doi:
10.1038/nature23902
Free here: Alternate evolutionary histories in the sequence space of an ancient protein - PMC
Abstract
To understand why molecular evolution turned out as it did, we must characterize not only the path that evolution followed across the space of possible molecular sequences but also the many alternative trajectories that could have been taken but were not. A large-scale comparison of real and possible histories would establish whether the outcome of evolution represents a unique or optimal state driven by natural selection or the contingent product of historical chance events1; it would also reveal how the underlying distribution of functions across sequence space shaped historical evolution2,3. Here we combine ancestral protein reconstruction4 with deep mutational scanning5–10 to characterize alternate histories in the sequence space around an ancient transcription factor, which evolved a novel biological function through well-characterized mechanisms11,12. We found hundreds of alternative protein sequences that use diverse biochemical mechanisms to perform the derived function at least as well as the historical outcome. These alternatives all require prior permissive substitutions that do not enhance the derived function, but not all require the same permissive changes that occurred during history. We found that if evolution had begun from a different starting point within the network of sequences encoding the ancestral function, outcomes with different genetic and biochemical forms would likely have resulted; this contingency arises from the distribution of functional variants in sequence space and epistasis between residues. Our results illuminate the topology of the vast space of possibilities from which history sampled one path, highlighting how the outcome of evolution depends on a serial chain of compounding chance events.
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I said no such thing.
But, yeah, maybe a little.
Still funny though.
Gauger writes in her response:
For evolution to be true, though, in case you are not comfortable with the above, it must have been possible to get new proteins from old, by many pathways. It must be possible to convert closely related structures to each other’s function; isn’t that the assumption of gene duplication and recruitment, of cooption?
I agree, it must be possible to convert CLOSELY RELATED functions to each other. Not functions that shared ancestry over half the forking lifetime of the planet ago.
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Something that bothered me was she said it would have to happen at the beginning. If it did, surely the two enzymes would be wayyyy more similar than 33%.
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: excessively or improperly intimate or exclusive:
mainstream fashion magazines have an incestuous relationship with advertisers
Now you’ve learned a new definition.
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Exactly. It just doesn’t make sense as a test of the scenario they are proposing.
I seriously have trouble giving so ill-conceived an experiment with so misleading a spin, a charitable interpretation. Look at this alignment of their chosen proteins:
What is the probability of multiple hits for two proteins this dissimilar?
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This is exactly my issue with this paper that DI has planted their flag on. @Agauger, what rationale was used in selecting the two different proteins? The two proteins used in the study share 34% sequence identity - barely enough to be considered homologous. I think it is reasonable to say that a better test of evolutionary theory would be to use proteins with a much greater degree of similarity. You and Axe changed roughly 11% of the approximately 260 amino acid differences and couldn’t make one enzyme function as the other. Your conclusion was that this was a clear demonstration of the limits of evolution, but as @Rumraket has stated, that is like jumping from squid to pig.
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It also makes no sense to ignore intramolecular epistasis. A deleterious mutation in one genetic background may not be deleterious in a different genetic background due to the interactions of amino acids within the same protein molecule. This is protein chemistry 101, and yet they ignore it.
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I would like to discuss this paper. Wouldn’t work like this also have consequences for their waiting-time argument? If there are multiple pathways, it seems that would decrease the waiting time pretty drastically. Makes me think of @glipsnort and his comments about it on biologos:
Glipsnort responds to a critical article - #2 - Faith & Science Conversation - The BioLogos Forum
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Yes that is one of the fundamental problems with the “waiting time”-type arguments. They focus on a specific outcome, as opposed any similarly complex adaptive outcome. It essentially always reduces to the Texas sharpshooter fallacy.
As I wrote in another thread, consider the difference between these two questions:
What is the probability that this specific gene G will be duplicated, and then later mutate through this specific loss of function mutation L, and that this particular other protein P will buffer against the loss?
What is the probability that some gene will be duplicated, and then later will mutate by some loss of function mutation, and that some other protein P will buffer against the loss?
My point is that for the probability argument against such scenarios to make sense, we’d have to know at least the approximate frequency with which the general case happens, as opposed to the odds of the specific. And the same goes for so-called “waiting time” problems. What is the average waiting time for the specific case, versus the average waiting time for any similarly complex case?
How often are genes duplicated? How often do duplicates suffer loss of functions mutations? How often do duplicate genes interact in buffering ways with other proteins? If we can answer these general questions we can calculate the frequency with which such events in general would be expected to occur given population size and so on. So while any one such event looks extremely unlikely, if such cases do occur in general with some appreciable frequency, the “waiting time” problem is completely misleading.
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Do you know of any more papers that demonstrate multiple pathways? Or different proteins or distinct folds that can perform similar functions?
Not off the top of my head.
Here is an interesting paper on multiple evolutionary pathways for pyrimethamine resistance in P. falciparum.
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Actually what comes to mind is that the malate and lactate dehydrogenases have evolved convergently, multiple times independently, from distant ancestors by different pathways in distinct eukaryotic clades.
Jeffrey I. Boucher, Joseph R. Jacobowitz, Brian C. Beckett, Scott Classen, and Douglas L. Theobald (2014)
“An atomic resolution view of neofunctionalization in the evolution of apicomplexan lactate dehydrogenases.”
eLife 2014;10.7554/eLife.02304 [ Open Access ]
doi:10.7554/eLife.02304
Phillip A. Steindel, Emily H. Chen, Jacob D. Wirth, and Douglas L. Theobald (2016)
“Gradual neofunctionalization in the convergent evolution of trichomonad lactate and malate dehydrogenases.”
Protein Science 25(7):1319-1331. [ Open Access , pdf]
doi:10.1002/pro.2904
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