Based on what?
Unbiased readers might actually read Behe’s book.
Here’s the link to the study Gauger cited. You tell me:
Try reading Behe’s book.
The answer is “zero”. They tested disease-causing mutations. This tells us nothing at all about how likely mutations are to be gain of function when they are adaptive.
I read his paper. Does he introduce much new data in the book?
It sounds like you are using “positive” in a different way from the abstract.
This could be a problem. For example, he cites a DNA study on finch beaks that shows that two mutations were responsible for the difference between sharp and blunt beaks. The authors of the study point to a computer analysis that says both mutations were damaging. But now I assume you will challenge the computer analysis.
But here’s a link to the finch beaks study:
They’re using positive controls to test the intended application of the program – detecting mutations most likely to cause disease. For that purpose, they’re using the right controls. You’re talking about using it for a completely different application, where that intended context does not apply.
I suggest you stop making assumptions about me.
Have you? What have you learned from the book that you believe is the strongest evidence for the concept of “Darwin Devolves”? I have shown you why the polar bear APOB evidence is not nearly as strong as Behe would have his readers believe.
Okay. I provided the link. You can read the paper and tell me what you think.
Yes, I’ve read the book. That when DNA studies have been done on species in nature, Behe’s first rule of evolution seems to hold. But we will have to agree to disagree on what the APOB evidence shows.
Here’s a list I put together from the index of Darwin Devolves of organisms in the wild where Behe says that DNA studies show there have been adaptive mutations that involved breaking or damaging genes:
Polar bears, finches, cichlids, humans, yersinia pestis, Trifolium (white clover), yeast, and woolly mammoths.
He also cites examples where articial breeding resulted in damaged or broken genes:
Dogs, cats, and horses.
He does mention one adaptive mutation in the wild that was not the result of a broken or damaged gene. Whoops! Two adaptive mutations. One each in:
Cichlids and humans.
Now perhaps he refers to other examples. Without re-reading the entire book, I wouldn’t know for sure.
Perhaps Behe has misrepresented the data. Perhaps there are lots more examples of adaptive mutations in the wild that have been shown not to involve broken or damaged genes. If so, feel free to point them out.
I don’t think Behe has ever claimed the the rule of adaptive evolution always holds which seems to nullify the importance of the rule. How do you see first rule as evidence supporting ID when Behe must admit that it doesn’t always hold true?
Since you have read the book, what else does he write that convinces you that APOB is strong evidence of ID? It seems highly arguable that PolyPhen 2 and the mouse study are really sufficiently strong scientific arguments to support his point.
Right, he only sees it as a rule of thumb. Let’s see if I can summarize his argument:
(1) Constructing new biochemical complexes almost always involves multiple non-damaging mutations.
(2) Damaging mutations happen much more often and much more quickly than non-damaging mutations.
(3) It is much more likely that Before an organism has evolved a new biochemical complex, it will have “solved” its evolutionary challenge by an adaptive damaging mutation.
APOB was only one of several (I think 17) highly selected genes in polar bears cited by the researchers as having probably damaging mutations, using the PolyPhen-2 study. But APOB is the one that ignites the most controversy for some reason. Nothing further about it in the book, except perhaps that it fits the pattern shown in the other DNA studies that Behe cites.
It might fit the pattern. There really isn’t enough yet known. It is an odd hill for Behe to plant his flag on, since it is still rather speculative.
Moving on from APOB, Behe gives a clearer presentation of his argument that damaging adaptive mutations are a challenge to Darwinian evolution in his reply to Lenski:
I think the moderators might allow me to quote one of the paragraphs:
"As I initially discussed in a book chapter and as I emphasize in Darwin Devolves, beneficial degradative mutations have a very strong, natural, built-in advantage over beneficial constructive ones, exactly because of their frequency of occurrence. Let me explain briefly here. Consider two genes, either of which when mutated would be beneficial for an organism to meet some particular selective challenge. The first gene (call it A) would be helpful if it mutated (call the mutated protein A*) at a particular residue of the protein it coded for to give a new constructive feature (perhaps a helpful new binding site). The second gene (call it B) would be helpful if it mutated (to B*) so that its activity were substantially degraded or eliminated entirely. Yet there are orders of magnitude — a hundred to a thousand — more ways to degrade B than to improve A. That means that if neither mutation were originally present in the population of a species, B* would be expected to appear in only a hundredth to a thousandth of the time needed for A* to show up. For example, if in this situation the time expected for a constructive mutation to arrive were a hundred thousand years, a degradative mutation would arrive in only one hundred to one thousand years. The result is that B* would have 99,ooo to 99,900 years to spread through the population to fixation before A* even showed up. If both A* and B* relieve the same selective pressure, then when A* eventually did show up there would be no more pressure to relieve, since B* had done so long before. Thus B* has a built in advantage simply because it is degradative — because its mutation rate is much higher.:
Curtis, would you be able to look this paper up and see what sort of computer program they used to determine that the two mutations that affect finch beaks were damaging?
@Bilbo, could you explain the significance of this thread in your eyes? I’m not really sure what the overarching point or excitement is- from my perspective I see ‘sometimes genetic changes break stuff, but that can often be beneficial to a population over time.’
Like we have lots of pseudogenes scattered throughout our genomes and that’s a good thing- we have remnants of genes for digesting chitinase for example and it’s fine that we don’t need those anymore. Some are bothersome like needing to take vitamin C thanks to a lack of selection pressure on that gene in the past in our lineage.
Help me out here Bilbo.
It’s called SIFT:
I thought it might be interesting and informative to see what kind of point was made at EN about this paper. I didn’t do a thorough search, but did find an article (here) that contains this quote:
All studies demonstrated the same basic results. First, the vast majority of adaptive mutations degrade or outright disable genes. For instance, the gene most strongly associated with the difference in blunt-beak verses pointed-beak finches is called ALX 1 . The only variation in it throughout all finch species is two mutations that both impair function.
First, ALX1 is indeed a homeobox gene that is important in craniofacial structure in birds and mammals. Additionally, according to the Nature article, loss of ALX1 causes loss of early craniofacial development in humans, so clearly this is a gene of interest. The EN report states “The only variation in it (ALX1) throughout all finch species is two mutations that both impair function.” This doesn’t seem to be the case by eyeballing the figures, but I haven’t done side-by-side sequence comparisons for all (or any) of the finches in question. In any case, the Nature paper does point out two clear candidates:
Two other changes constitute missense mutations (L112P and I208V) at ALX1 amino-acid residues that are highly conserved among birds and mammals
The analysis performed on these missense mutations is done by a tool called SIFT (Sorting Intolerant from Tolerant). Full confession - I am not even a novice when it comes to using SIFT or PolyPhen 2, I can just see what the tool is used for, just like anyone else that takes the time. But the SIFT analysis is rather similar in output to PolyPhen 2 - it categorizes mutations based on likelihood of disrupting function of the wt gene, and there is no way to determine if these changes are “positive” or “negative”. You can learn more about SIFT here. And this is a quick set of instructions for interpreting data from one of the samples provided at the website:
#+ means substitution does not alter phenotype
#- means substitution affects protein
#+ - and -+ do not affect protein as severely as “-”
#order of severity : - > -+ > + - > +
The ALX1 mutation in question were give a score of 0.3, but I honestly don’t know how to interpret that. Regardless, we see the same issue as seen in PolyPhen 2 - missense mutations can be categorized as “not affecting” or “affecting” phenotype, but those that are “affecting phenotype” cannot be categorized further into the “positive” vs “negative” categories that would be important support for Behe’s “first rule”.
PolyPhen 2 was being discussed at Peaceful Science recently and @T_aquaticus made a very important point - “I think it is also worth mentioning that even an intelligent designer would not be able to change a genome in a way that PolyPhen would consider beneficial.”
Sensitivity measures the true positive rate and specificity measures the true negative rate. My working assumption is that a true positive in this context means that Polyphen-2 labeled a positive change as not neutral, which means that it applied the label of “damaged” because that’s the only label it uses other than “neutral.” Likewise, a true negative means that Polyphen-2 applied the “damaged” label rather than the “neutral” label.