Polar Bears Again, Is Behe Vindicated?

[swamidass (S. Joshua Swamidass)]

Another article comes out on Polar Bear ApoB. I honestly lost track of all of them at this point. Once again, unsigned:

https://evolutionnews.org/2019/05/polar-bear-seminar-new-evidence-that-behe-is-right/

[swamidass (S. Joshua Swamidass)]

What are your thoughts @Art and @NLENTS? This one is primarily about me though. They respond to this post by me: Is Polar Bear ApoB Damaged?. So I will read it closely and respond in detail later.

[T_aquaticus]

From the ENV article:

In fact, multiple medical studies have found that unequivocally damaging mutations in APOB lead to truncated and poorly functioning versions of apoB proteins that are associated with lower cholesterol — perhaps related to the sort phenotype seen in polar bears!

This is not the phenotype seen in polar bears. Serum cholesterol levels in polar bears is comparable to brown bears. The human phenotype they are pointing to results in drastically reduced cholesterol in humans, but that is simply not seen in polar bears. Therefore, this comparison is not valid.

Again, from the article:

The post on APOB linked above answered these critics in great detail. Biologist Joshua Swamidass has now written a response titled “Is Polar Bear ApoB Damaged?” There, he likewise asserts that the idea that Liu et al. believe APOB to be damaged “is totally and utterly false.” His lengthy discussion is appreciated, but he did not meet our request that the critics provide language from Liu et al. where the authors contradict their own findings and state that APOB was not damaged.

Let’s take a look at the actual paper:

Five of the nine cluster within the N-terminal βα1 domain of the APOB gene, although the region comprises only 22% of the protein (binomial test p -value = 0.029). This domain encodes the surface region and contains the majority of functional domains for lipid transport. We suggest that the shift to a diet consisting predominantly of fatty acids in polar bears induced adaptive changes in APOB , which enabled the species to cope with high fatty acid intake by contributing to the effective clearance of cholesterol from the blood.
POPULATION GENOMICS REVEAL RECENT SPECIATION AND RAPID EVOLUTIONARY ADAPTATION IN POLAR BEARS - PMC

The authors concluded that there was an increase in the clearance function of APOB in polar bears.

What is ENV’s response to this section of the paper:

We’ll return momentarily to Behe’s point that cholesterol may be removed by damaging APOB . For now, the point is that Swamidass is putting words in the authors’ mouths when he claims they concluded that APOB was not damaged .

The authors concluded that there was an increase in clearance of cholesterol in the blood. The real question is if Behe would call this a damaging change. I would assume not.

[Art (Arthur Hunt)]

Some people gotta blast. Me, I download and map.

So, I downloaded the reads from two animals and mapped them back to the polar bear NCBI sequence. The consensuses from these mappings lack the amino acid changes seen in Table S7 of Liu et al. This is very preliminary, but it is looking more and more like Table S7 has variants that are not widely distributed in the population. Which would mean that the polar bear APOB (I am not going to bother with the other genes) actually has none (I repeat - NONE) of the variants Behe claims will break the protein.

i will probably do more animals, at least until I find one of the variants in one of them. I will keep the board posted as I slog through this.

[NLENTS (Nathan H. Lents)]

@swamidass

I honestly lost track of all of them at this point

Me too. If there’s anything new, do let me know, but at this point, that seems pretty unlikely.

[swamidass (S. Joshua Swamidass)]

The key thing is we need to start writing our final post, to bookend the whole thing.

[swamidass (S. Joshua Swamidass)]

I may suggest we do the polar bears and malaria seperately.

[Edgar_Tamarian]

I deliberatly was absent from duscussion for while, because of insults i recived here, However, since this paticular topic is the one that i participated, i will contine to look at it

and why not to say that Science does not care who, where at his home, at his office or at his car downloaded and mapped…Science does not work that way, Your mappings would be valid if you present published results. But this is all that you all could say this means you all failed to respond the last ENV article which is summarised …here Polar Bear Seminar: This Is the End

[NLENTS (Nathan H. Lents)]

Also so that we can fully move past this, as they seem ready to do. I’m glad we didn’t fall into the trap of trying to respond to every one of their posts. Even without reading them all, there is a stunning about of repetition and redundancy to all of them. We obviously got them pretty stirred up, but is anyone buying any of it? They’re throwing a lot of pasta at the wall (or, actually, the same noodles over and over), but is any of it sticking? I’m trying to keep an open mind but none of it has given me pause.

[swamidass (S. Joshua Swamidass)]

The key thing to keep track of is the moving goal posts. This is about Behe’s book. Every argument and peice of evidence they add is an admission his book did not make the case. Every change of claims, also, is a concession that they could not defend Behe’s original point, every unsigned post, moreover, need not be engaged by us.

[Roy (30-year veteran)]

I’ll save time and apply Betteridge’s law.

[Sarah_Rodriguez]

Im particularly interested in @swamidass response regarding polyphen unless that was given already ““Polyphen does not attempt to predict ‘biochemical damage’.” That’s wrong”

[swamidass (S. Joshua Swamidass)]

They misunderstood PolyPhen. I’m a computational biologist, so this is solidly my area. Behe is outside his field. Just saying I’m wrong and quoting back the classification features is not a valid way to overturn our understanding of PolyPhen.

How did this happen?

My best guess is that they quote mined the author. Then, when we pointed this out, Behe painted himself into a corner. It seems he never admits error, so we are stuck.

We are still thinking through our final response. And I hope it will tie up loose ends. There have been so many articles on this that I want to go coallate them too.

[Faizal_Ali]

@swamidass

The key thing to keep track of is the moving goal posts. This is about Behe’s book. Every argument and peice of evidence they add is an admission his book did not make the case. Every change of claims, also, is a concession that they could defend Behe’s original point

Yes, which is his modus operandi. Look at how many changes the definition of “irreducible complexity” has undergone.

[Faizal_Ali]

@NLENTS

We obviously got them pretty stirred up, but is anyone buying any of it? They’re throwing a lot of pasta at the wall (or, actually, the same noodles over and over), but is any of it sticking? I’m trying to keep an open mind but none of it has given me pause.

I often wonder if their incoherence and inconsistency is part of the point, or if at least coherence and consistency are not important objectives for them. I spend a lot of (too much?) time debating creationists, and they rarely seem to even understand the arguments ID’ers are making. Rather, they will say “Well, sure, scientist X said this, but then Behe responded with this article here, so that takes care of that”, without even bothering to demonstrate that Behe (or whoeve) has addressed the pertinent points. The impression I get is that they are just bamboozled by the amount of “scientific” verbiage and jargon thrown at them and figure they can’t understand it, but Behe is a scientist so he must understand it, and that’s good enough.

[T_aquaticus]

@Art

So, I downloaded the reads from two animals and mapped them back to the polar bear NCBI sequence. The consensuses from these mappings lack the amino acid changes seen in Table S7 of Liu et al.

If memory serves, that’s what I saw when I looked at the NCBI sequence. None of the variants in Table S7 are in the NCBI sequence, as far as I could tell.

Thanks for slogging through the data. It’s much appreciated.

[evograd (Blogging Graduate Student)]

Do want to add anything to this thread from last month?

Repeating analysis of human APOB

While studying how Polyphen-2 works, I noticed that one of its features is to use a sequence comparison to help assess the effect of a mutation in a human protein. This made me wonder if the polar bear gene was included as a homolog in the analysis back before the 2014 Liu paper was published. Further I wondered if any new data has come out or any new updates would allow a new prediction by Polyphen for the exact same polar bear mutations. Basically, let’s repeat the Polyphen analysis for the following “damaging” mutations: Gene Position Ancestral Polar bear HDivPred APOB 716 N K possibly damaging APOB 749 D E possibly damaging APOB 2623 D N probably damaging APOB 3920 T P possibly damaging APOB 4418 L H probably damaging [PolyPhen2-716] [716-alignment] It is predicted exactly the same, which makes it seem like nothing has changed since it is giving the exact same probability to 3 decimal places. We can see the homologs used in the alignment, but I did not find…

[Giltil (Gilbert Thill)]

@T_aquaticus

This is not the phenotype seen in polar bears. Serum cholesterol levels in polar bears is comparable to brown bears. The human phenotype they are pointing to results in drastically reduced cholesterol in humans, but that is simply not seen in polar bears. Therefore, this comparison is not valid.

Several points

1. the human phenotype they are pointing to results in drastically reduced cholesterol in humans ONLY WHEN THE TWO APOB ALLELES ARE FUNCTIONALLY DEFICIENT. But heterezygous APOB deficiency in human result only in a mild cholesterol reduction.
   https://www.ahajournals.org/doi/pdf/10.1161/CIRCGEN.118.002376
2. Serum cholesterol levels in polar bears is comparable to brown bears DESPITE THE FACT THAT WHITE BEARS HAVE HIGHER FAT DIET THAN BROWN BEARS. So, metabolic changes are expected in polar bears to accomodate for this higher fat diet, metabolic changes without which too much cholesterol would be present in the blood of polar bears.
3. if you combine points 1 and 2, you will see that the comparison made in the ENV article is valid and that Behe’s case regarding APOB in polar bears is strong.

[T_aquaticus]

@Giltil

the human phenotype they are pointing to results in drastically reduced cholesterol in humans ONLY WHEN THE TWO APOB ALLELES ARE FUNCTIONALLY DEFICIENT. But heterezygous APOB deficiency in human result only in a mild cholesterol reduction.

Is this the case in polar bears? Are the individual polar bears homozygous or heterozygous for the specific variants?

@Giltil

Serum cholesterol levels in polar bears is comparable to brown bears DESPITE THE FACT THAT WHITE BEARS HAVE HIGHER FAT DIET THAN BROWN BEARS. So, metabolic changes are expected in polar bears to accomodate for this higher fat diet, metabolic changes without which too much cholesterol would be present in the blood of polar bears.

Humans who are homozygous for the APOB deletion never attain normal cholesterol levels no matter how much fat they consume, so this argument isn’t relevant.

[Giltil (Gilbert Thill)]

@T_aquaticus

the human phenotype they are pointing to results in drastically reduced cholesterol in humans ONLY WHEN THE TWO APOB ALLELES ARE FUNCTIONALLY DEFICIENT. But heterezygous APOB deficiency in human result only in a mild cholesterol reduction.

Is this the case in polar bears? Are the individual polar bears homozygous or heterozygous for the specific variants?

My understanding of the discussion around APOB in polar bear is that some adaptive mutations were fixed in the polar bears population precisely because they were adaptive. So I would rather say that the current population of polar bears is probably homozygous for the specific variant. This being said, it is easy to imagine how an APOB homzygous variant in polar bear can result in the same phenotype than an heterozygous loss of function variant in human. For example, such an outcome would be obtain if the homozygous variant (allele) in polar bear would result in a 50% activity reduction as compared to the wt allele.