One of the interesting findings in the study on mice is that animals that were homozygous (i.e. have two copies) for the knockout ApoB mutation did not make it past the fetal stage. They had severe developmental issues. I would assume that there are many polar bears who are homozygous for the mutations in question, and they have no developmental issues. This is a big red flag. I don’t think the mouse study can be directly applied to polar bears.
I’m in for that kind of thing. Once again, what Behe has done is an extreme cherry pick… in a paper detailing all the problems with APOB-deficient mice, he found one result that could, maybe, if you squint long enough, indicate that reduced APOB activity improves cholesterol clearance. The problem is that the paper didn’t look at cholesterol clearance, so it doesn’t support his position directly. Another problem is that simply having lower plasma triglycerides does not indicate overall better cardiovascular health. A person (or a mouse) can be very very sick, but their LDL levels look good (low), particularly if they are undernourished. In fact, when someone is critically ill, the chemical composition of the blood can start to go haywire in unpredictable ways. Some of the individual items may look fine in isolation, but the overall picture will be a picture of very poor health, as those mice were. Honestly, Behe might have a very lucrative second career in the picking of cherries - he has a real talent for it!
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Um, the yolk sac likely has nothing to do with the phenotype Behe is ignoring.
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I think Behe would argue that the “damaging” mutations, even in homozygotes, only lead to a 50% reduction in activity (whatever that may be).
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On a different tangent, a 50% increase in activity can also be deleterious in different circumstances.
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True enough. This applies to a few of the genes I work on …
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@NLENTS you should collaborate with @swamidass and @Art on this as it will help you to become a more widely known, lesser known scientist. 
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You are again NOT reading my post**
in Farese et al it says
In both species, apo-B is expressed in the yolk sac ; however, the yolk sac plays a different developmental role in the two species. In the mouse, the yolk sac becomes part of the membranes that surround the developing embryo and contact the maternal tissues early in gestation, whereas in human embryos the yolk sac is a less prominent organ
An aside that I hope doesn’t distract too much…
By chance, I’ve just sat through a few seminars that discuss functional roles of the ‘disordered’ regions of proteins. One role that’s interesting (to me) is in forming lose connections or gel-like regions in the cell. This type of configuration has interesting impacts on regulation. What’s nice is that we’re developing the biophysical tools necessary to understand more about their dynamics (a nice application for computational modelling, @swamidass).
The relationship to this discussion is…
We often talk about disrupting the folding of an ‘organized’ protein as having a negative or ‘damaging’ effect. And certainly, in some cases that can increase the protein’s turnover in the cell. However, there are also clearly instances where this change is a positive effect. And in fact, that we know of roles for disordered regions suggests that changes that disrupt parts of a protein’s structure is another way for ‘functions’ to be acquired and/or changed.
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In your own words, @Edgar_Tamarian, could you explain the connection between the yolk sac and sperm functionality? That may help clear up some confusion here.
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In Reality, you are cutting the quote to sound Behe what you like to him be sound
in Darwin devolves we read the opposite.
Since few experiments can be done with grumpy polar bears, they analyzed the changes by computer . They determined that the mutations were very likely to be damaging —that is, likely to degrade or destroy the function of the protein that the gene codes for…Computer analysis of the multiple mutations of the gene showed that they too were almost certainly damaging to its function. In fact, of all the mutations in the seventeen genes that were most highly selected, about half were predicted to damage the function of the respective coded proteins
as also Behe explains
Professor Lenski points out (as I repeatedly do in the book) that the computer analysis is a prediction that a particular mutation will or won’t be damaging; it is not an experimental demonstration
He precisely addressed here
The APOB gene of polar bears is mutated with changes that were predicted by computer methods to be damaging. A 1995 study showed that a mouse model that had one copy of the APOB gene knocked out actually had lower plasma cholesterol levels and increased resistance to hypercholesterolemia from a high fat diet. If the polar bear mutations acted to lower the activity of its own APOB, a result similar to that for the mouse might be expected. Thus there is no good reason to speculate about new functions
Trollhoffer recently called me “somewhat prominent.” I dunno. I think I preferred “lesser known.” But at least I’m not “some other guy” (@art). I’m actually surprised that Behe didn’t remember him from the T-urf13 bit.
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I think someone needs to remind Behe of the First Law of Holes.
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lol, very true. It’s a natural consequence of their “never admit any mistakes” posture that they find themselves in untenable arguments.
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Let’s fix this to account for some more information:
“The APOB gene of polar bears is mutated with changes that were predicted by computer methods to be damaging. A 1995 study showed that a mouse model that had one copy of the APOB gene knocked out actually had lower plasma cholesterol levels and increased resistance to hypercholesterolemia from a high fat diet.”
Two other studies of the heterozygous mouse model - published in 1995 and 1996 - showed that these mice had significant defects in male fertility. If the polar bear mutations acted to lower the activity of its own APOB, results similar to those for the mouse might be expected.
Of course, this is where the wheels fall off for Behe.
The 1995 study did not look at the specific mutations in the polar bear ApoB gene. There has been no experimental verification that polar bear ApoB has less function than brown bear ApoB. Computer model predictions need to be verified by experiment, especially when there are other mutations that can compensate for damaging mutations.
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Yes. This is one of the things I think about with respect to the poly(A) complex. The plant proteins have several with predicted unstructured regions, and they involve subunits whose functions seem to have diverged greatly from what is known about their roles in mammals.
No, it is speculation.
They eat an incredibly high-fat diet.
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I highly doubt that Behe will ever discuss that subject publicly.
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There was no computer analysis done that “showed that they too were almost certainly damaging to its function.” Behe misread the results. Do we need to over that again too?
Behe still states:
They concluded…
Who is “they” if not the researchers? Behe could clarify for us. He has not.
No. He did not address the fact that unequivocally (unintentionally or not) misrepresented the authors.
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