Part 2 of Polar Bear Seminar

Design
(Bill Cole) #74

Can you expand on this?

(Dave Carlson) #75

I and others have done so repeatedly, even in threads you were participating in. In brief:

Behe’s hypothesis is that adaptive evolution proceeds primarily via mutations that degrade molecular functions instead of improving them. The chief example he gives in the beginning of his book is the APOB protein (among others) in Polar bears, which appears to be under positive selection. To support this example, he uses predictions from PolyPhen, a program that examines sequence alignments to predict functional changes in proteins. If a variant is not predicted to change any amino acids, PolyPhen calls it benign. If a variant does change an amino acid, this is evidence of a potential functional change, and PolyPhen will label this change as either “possibly damaging” or “probably damaging.”

Thus, PolyPhen is incapable of producing a result that contradicts Behe’s hypothesis. Either a mutation will not change the protein and be labeled as benign (and is thus unlikely to be under positive selection) or will change the protein and be labeled as damaging. There is no possible way for PolyPhen to predict an enhancement in function, so the results cannot be used to determine how frequently adaptive evolution proceeds via degrading function versus improving function.

Basically, Behe has set up a “heads I win, tails you lose” scenario.

That isn’t how science works.

Edit: I want to add that I missed the fact that some variants that change the protein can be labeled as benign, based on the level of conservation at the site and the likelihood of structural changes. Still, there is no category of “enhanced” function or anything like it.

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(Bill Cole) #76

Can you make the case that a change to current function will not be damaging in most cases?

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(Arthur Hunt) #77

Replying to myself:

EN says here:

Second, Behe’s critics are making a big deal about his not showing the data in the table where mutations were predicted to be “benign” — but benign or neutral mutations don’t challenge his thesis . Data only challenges Behe’s thesis when a mutation is shown to be constructive. In this regard, it’s crucial to point out that the mutations that Behe didn’t list from the chart that were not said to be damaging were also NOT said to be “constructive.” They were said to be “benign.” That’s a key point that completely undermines Lents’s charge that the data Behe doesn’t list is somehow “contrary” to his position.

However, ALL of the mutations listed in Table S7 of Liu et al. are in genes that show clear indications of being under positive selection. While benign mutations in these genes may be neutral, they may also be beneficial or constructive. Indeed, to cite an example from the data Behe omits, at least one of the benign changes in the polar bear OR5D14 gene must be constructive or beneficial, since this gene that is under positive selection only carries mutations flagged by PolyPhen2 as benign. To give another example, the sole missense mutation in another gene under positive selection – EHD3 – must be beneficial or constructive (PolyPhen2 flags this change as benign).

Just how does the data Behe omits affect his thesis? From this essay:

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.

(Bold emphasis added to point out the actual numbers Behe is thinking of.)

In other words, for every benign and beneficial mutation, there should be 99-999 damaging mutations. If one considers all of Table S7, and not just the parts Behe presented in his first response, then we see easily that Behe is quite completely wrong in his assertion. There are 23 benign missense changes, 15 predicted to be either possibly or probably damaging, and nine with conflicting predictions. As we see from the above (and from closer perusal of the Table), at least three of the benign changes MUST be constructive or beneficial, and the number likely is much greater. This is plainly not in line with the numbers Behe asserts.

The bottom line is, the parts of Table S7 that Behe omitted plainly conflict with his ideas and claims.

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(Dave Carlson) #78

That’s a good point. I didn’t realize missense mutations could fall under the category of “benign”.

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(S. Joshua Swamidass) #79

Alright @discovery_institute, here is my answer (again): Is Polar Bear ApoB Damaged?.

Please stop misrepresenting these poor authors. The evidence is so trivially against the claim that they agree with you, it is best to just apologize and stop.

Constructive neutral evolution demonstrates that Behe’s argument fails because he neglects that neutral mutations are often constructive. This is one of the important facts we can see on display in the ENCODE data.

I encourage ENV to look at some of the first responses to Behe’s work, which were spot on:

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(Blogging Graduate Student) #80

That’s… how circular reasoning works. The point is that the interpretation in question can’t support the initial hypothesis if it assumes the initial hypothesis as a premise. If there’s independent evidence supporting claim 1, that’s what should be focused on, not this.

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(Arthur Hunt) #81

All of the mutations in Table S7 are missense.

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(Dave Carlson) #82

Got it. I work with SnpEff quite a bit, so I was thinking that PolyPhen was more similar to that method than it actually is.

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(Edgar Tamarian) #83

I have read your post, I am now happy that you completely refuted @NLENTS claim that Behe misrepresented the table 7 by cutting off, since the table does not provide any positive evidence that mutations are constrictive, If there is no positive evidence in the table for constructive mutations what was the purpose of hiding the rest of the table?, So, that was false accusation which was no relevance to the issue at all, just to shift real discussion into the discussion that Behe has a hidden agenda. But, now I am happy, ENV was able to force all of you to admit the falsehood of the accusation and to return real science discussion. You made good points, and I am sure that your points will be addressed. Even though, it was already addressed by Behe with post reply to Lenski.

#84

Behe and ENV did misrepresent that table. They claimed that those were conclusions. They weren’t. They were observations.

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(John Mercer) #85

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(Blogging Graduate Student) #86

As I said when I pointed out the altered table 2 months ago:

Are we supposed to believe that Behe did that little switcharoo without thinking that a large fraction of his lay readers would just see a big list of entries saying “damaging” and come away with the impression that these were the majority of variants, or even all of them?

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(Nathan H. Lents) #87

Well, as long as you’re happy!

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(Edgar Tamarian) #88

Scientific conculsions should be based on observations, is not it?

The problem of biology is it does not much realy on observations but realy on the theory that was put forward in 1859. That makes conlusions be felxible, if an observation at sightest supports the theory, it is accepted, if observations do not support theory, the concusions are drown not from the observation, but imaginary wishfull thinking that fits the theory

#89

Conclusions should be based on observations, but that doesn’t mean you are allowed to misrepresent observations as conclusions. Behe claimed that he agreed with the conclusions of the paper. That wasn’t true. Behe took the same observations and arrived at the opposite conclusion to that found in the paper. Behe tried to give his claims more credence by claiming he agreed with the authors when in fact he doesn’t agree with them.

Baseless accusations aren’t worth much.

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(Edgar Tamarian) #90

the conclusion of the paper does not say mutations are constructive, it just makes suggestion that mutations had certain effect, but that effect you can come either by constrictive mutations or by degradative mutations. Behe claims that the effect is due to degradative mutation by replying on the observation made in the paper

#91

Where does the paper say that?

(Edgar Tamarian) #92

First, the paper does not say mutations are constructive

Second, a scientist can read already published works and can make conclusions, observations that are not explicit in the paper more explicit to a wider audience,

Third, Yes, the author of the paper did not write explicitly that certain effect, is due to degradative mutation, but the author of the paper did not write certain effect, is due to constructive mutation either.

Forth, Behe just made what was implicit in the paper more explicit, which itself neither contradicts observations made in the paper nor the conclusion of the author.

(S. Joshua Swamidass) #93

@Edgar_Tamarian why do you care so much? Why are you carrying water for them?

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