A Scholarly discussion of ApoB

I note with interest the discussion of ApoB in the Scholars forum. The paper posted in the OP is a pretty interesting and comprehensive discussion of all the known mutations in ApoB. All of them degrade its function. From whence the confidence that somehow in polar bears ApoB mutations are likely to be constructive, I surely cannot fathom.

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On what basis do you assert that it covers all known mutations, Ben? I don’t see anything of the sort in the paper.

From my first skimming, it appears to be covering a subset of pathogenic mutations, not all mutations.

I think you’re engaging in wishful thinking.

Can you fathom how many known APOB variants exist?

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Since the paper focuses on mutations that cause disease, this is to be expected. If you saw a report on the crime rate in the city, would you take that as evidence that no one does anything nice in that city?

There is also a serious bias towards detecting mutations that cause disease. It’s a lot easier to find people within a population who are sick. It’s much harder to find people who are feeling healthier and then be able to match that increase in health to a specific mutation.

Polar bears don’t show the effects of deleterious mutations in ApoB. That is where the confidence comes from.

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I went over to Ensembl and took a look at the variant table for human ApoB. There were so many known and naturally occurring missense mutations in the human population that I had to export the table to Excel just to get a count. There are over 4,000 known variations in the amino acid sequence of ApoB in the human population. Hopefully that puts the handful of mutations in the review paper into context.

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You’re right. I was careless with my words.

What is this?

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I see. ApoB seems to have a very complex mechanism. What sorts of effects would you expect a degradative mutation to have? Hyper or hypocholesterolemia aren’t the only ways to degrade such a complex mechanism. Is that all you meant?

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Interesting. How many of them are degradative, neutral and constructive? Or maybe how many would you predict are in those categories?

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That’s gracious of you.

It’s a deleted post, left over when I merged it with the one above.

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You can look at 642 alleles at OMIM:
https://www.ncbi.nlm.nih.gov/clinvar?term=107730[MIM]

It’s very hard to know. However, it’s essential to keep in mind the different contexts in which these alleles were found; for the patients they are searching in those with dyslipidemia, while for the polar bears they are looking in regions that have been strongly selected in normal individuals. Thus, it would be completely illegitimate to use the spectrum found in the former set as a template for predictions for the latter set.

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I expected that kind of reply. I was referring to T_aquatica’s search showing 4,000 variants though. I realize this is in one species whereas polar bears and brown bears are a different species, though I’m not sure how much different they are from each other compared to different human populations. I’m really not looking for a hard prediction. I’m just curious whether you think there might be any mutants both beneficial and constructive in that set.

It seems the main difference between IDists and evolutionists is our differing intuitions about the prevalence of constructive, beneficial mutations. I would look at that group of 4,000 and guesstimate 0 beneficial, constructive mutations, with “constructive” defined as a novel functional coded element (FCE) as Behe defines it. I was only wondering if you would expect more than 0 or agree with me.

The main difference between IDCreationists and scientists is that the former group consistently presents false assumptions as facts and refuses to test hypotheses, while the latter group consistently gathers facts and tests hypotheses.

And your guesstimate would be based on nothing more than wishful thinking.

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This is right, but the difference is actually not that great. Scientists and those that accept their conclusions on evolution (I am avoiding use of the bizarre term “evolutionists”) freely acknowledge that it’s way easier to harm a gene or protein through unguided mutation than to effect positive or creative change. We all agree on that. We also agree that sometimes these “damaging mutations” (also not a term we would use that much because the reality can be much more nuanced) can sometimes lead to fitness gains. The only real difference between Behe and the scientific community is that he claims that harming things is pretty much ALL that unguided mutations can do and that to achieve any gain-of-function (and he uses a single disulfide bridge as a regular example), something more than random unguided mutation is needed.

To answer an earlier question in this thread, there are two important pieces of suggestive evidence that the cholesterol-clearing function of ApoB is enhanced in polar bears: one is that they eat a diet very high in saturated fats and yet have low LDL levels and do not develop cardiovascular disease. Their cholesterol clearance must be working very well and the ApoB gene harbors the second-most highly selected variants in polar bears - highly suggestive. Secondly, the variants themselves are mutations that cluster disproportionately in the domain that we know is involved in cholesterol clearance. Again, highly suggestive.

Also, you ask about the thousands of variants and how many of them are “damaging.” That’s just not something we can know without exploring each variant one-by-one in the lab. The computer predictions are just not there yet. They predict the type of mutation (missense, etc.) and then attempt to say if it alters the domain structurally and call it damaging if it looks like it does. You see the problem there, right? While most mutations that cause structural change will weaken the function of the domain, some will bring enhanced or modified function. While more rare, these are more important than your average damaging mutation and so when they do appear, they often get selected for and accumulate in the population. Behe and other IDers are putting way too much stock in the PolyPhen predictions simply because a superficial look at the results support the position that they want to be true. It’s confirmation bias, pure and strong.

I also want to point out that the few times that Behe has acknowledged the creative new-function effect of genetic rearrangements, like occurred in the citrate+ mutations in the LTEE (which he acknowledged) or the tURF13 ion channel (which he hasn’t), he chides scientists for confusing WHAT happened with HOW it happened. So, even when we are lucky enough to capture one of these events in such a way as to figure out with relative certainty how they unfolded, Behe fires back, “yeah, but you can’t show it wasn’t guided.” Here’s a direct quote (although talking about feathers, not molecules): “It never ceases to amaze me that Darwinists like Coyne are unable to separate the question of what happened from the question of how it happened.”

Ultimately, he’s right. Down to the precise molecular events, the breaking of the DNA strands, the DNA polymerase grabbing the wrong nucleotide… we can’t know whether or not the hand of G-d was involved or not. If it was, that leads to some pretty uncomfortable conclusions as far as I am concerned, but if people want to believe that mutations and genetic rearrangements are all intended and executed by a supernatural force, that’s totally fine. But what we can’t do is pretend that this is a valid scientific approach.

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Thanks, as always, for this thoughtful reply, Nathan. As one whose attitude and understanding has been greatly affected by the dialog here (at PS over time), I really appreciate what you are saying. I came to PS because I wanted to see if there wasn’t some sort of unified theory of how things got here, what degree of agreement exists, and how such a philosophy might be articulated to the laypeople who are interested in this topic.

Many of us can envision the hand of God being involved in some way regarding the structure of the cosmos, the origin of life, and its evolution over time. If and how that happened may never be known for certain. But when we have a voice which carries authority (such as yours or Joshua’s) that merely leaves open the possibility of God’s involvement, it keeps open the door for a peaceful dialog, and also the minds to develop a greater understanding of the work that you in the science community are engaged in.

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The door on God’s involvement is as open as the door on leprechauns, Muad’Dib, fairies, Santa Clause, Gandalf, the flying spaghetti monster, and Obi-Wan Kenobi.

I’ll note that nobody has answered my question.

@NLENTS

I have wanted Behe to respond to Hunt’s stuff on tURF-13 ever since I first read it years ago. But I will say for myself that I think tURF-13 does look designed to me. That does not mean I think God miraculously causes those mutations directly. What I would hypothesize is tURF-13 is the result of what James Shapiro calls natural genetic engineering. In other words I would predict a mechanism similar to the immune system that mixes and matches genetic modules until it gets something that solves the problem was involved. This is in principle a testable prediction, and that is a valid scientific approach.

That’s not what we mean by a testable hypothesis. The prediction must be empirical–that is, what you will directly observe, with no wiggle room for interpretation.

Do you have an empirical prediction?

I am quickly ceasing to care what you mean.

So, @Rumraket, are you saying that you can, from science, know for certain that God was not involved at all? Leaving out the leprechauns, etc., for now at least. This seems to fly in the face of what Nathan said.

No, I can’t know that for certain. That doesn’t mean there are any good reason to even entertain the idea any more than the rest of the options I listed. There’s an infinite list of conceivable dial-twichers hiding behind the scenes. I could be causing these mutations with my telekinetic powers too, can you really know for certain that I’m not?

No, I cannot. Not from science anyhow. From the perspective of science, it is equally likely that you and Obi-Wan possibly are in cahoots with one another. It may be less likely for the leprechauns and Santa, however.

The point that I was trying to make is that it is refreshing to read a conversation over science that does not overstep its bounds and, as such, become exclusive to many groups of people. And, if you happened to be flipping the switches… well that’s a nice bit of work! Kudos!

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