I don’t have much criticism. They didn’t have data on direct function, so they employed an algorithm for a very crude initial analysis:
Their goal wasn’t to determine the specific functional roles of the mutations they found. This was an initial sweep of the entire polar bear genome that was meant to find genes that are potentially under selective pressures. Their other goal was to tease out the population dynamics of polar bear speciation. They used PolyPhen as a way of guiding future research, and it was never meant to be the final say on the actual causal role of those specific mutations.
As many here understand, not all conclusions are created equal. There are strong conclusions and weak conclusions. It is up to the reader to determine the strength of those conclusions, and Behe failed to do this, at least in my opinion. It isn’t enough to simply repeat what the authors write and act as if it is gospel. The quality of the conclusion matters.
If you read the other thread, I climbed out of the APOB black hole just before I reached the event horizon. The point of no return in this case is the point where you start looking at KEGG pathways and the spider web of protein interactions across different tissues and organs. What is interesting is that polar bear and brown bear cholesterol levels seem to be in the same range with the number of data points available. If a group of scientists measured cholesterol levels in 1,000 polar bears and brown bears we might see a statistical difference between the groups, but the error bars overlap at the moment. In other words, we don’t see evidence of a stark difference in cholesterol levels between polar bears and brown bears, at least not at the levels we see in human cases of hypo and hypercholesterolemia.
Yes, but the message from here on should be simple:
Behe’s a biochemist. He screwed up in his representation of the paper, so the obvious thing to do is for him to do biochemical assays to test his hypothesis. That’s how people who still do science behave. Period.
Well, I’m not sure if that’s really germane because I think we all agree (Behe included) that polar APOB is almost certainly involved in protecting them against hypercholesterolemia in the face of a diet high in saturated fats. I think the disagreement is in the nature of the APOB mutations - do they enhance removal of cholesterol in the blood, or do they cripple APOB-mediated loading of cholesterol into the blood (a possibility you mention above). The former would refute Behe, the latter would support him, BUT… it would require other enhancing alterations (because otherwise, the dietary fat just stays in the gut and they poop it out?). There’s no sign of those other alterations that would compensate for the diminished APOB in the list of highly selected gene variants. So this is a real stretch.
I have always maintained that it’s possible that APOB is somehow functionally diminished in polar bears, compared to brown bears. What I am saying is that there is no evidence that it is and that the available evidence argues otherwise. New evidence could change that, for sure. But the additional analysis we’ve done here in this thread and others is adding more weight on the scales. Not that this will stop the DI from trying to pretend otherwise.
APOB is involved in getting lipids out of your food and into your body. APOB is also involved in getting APOB out of your serum and into your cells. It isn’t clear if mutations in polar bear APOB are affecting any of these functions. Liu et al. speculated that changes in polar bear APOB helped the species cope with a high fat diet, but it is just a speculation. They also weren’t clear on the specifics of how this might occur.
If it were me, I would state that PolyPhen predictions don’t allow for any solid conclusion about the actual function of polar bear APOB, and cholesterol levels in polar bears certainly don’t show any signs of obvious cholesterol dysregulation such as hyper or hypocholesterolemia. They want to argue that PolyPhen is strong evidence, but it just isn’t.
do favor please, repost that original post here for me to compare to see whether they responded the original challange or not, there were so many post on plar bears in recent month that i am confused which post you think is the original one
We could look at the conclusions the authors of the paper drew from the data:
The authors of the paper concluded that APOB had increased function, not degraded function.
We all agree that the PolyPhen algorithm lists certain mutations as being damaging. What we disagree with is the conclusion that PolyPhen makes reliable predictions. The challenge is to show that APOB is actually affected in a negative manner. At least with the gene related to white fur we could see a phenotype, but Behe makes no connection between the mutations in APOB and an observed phenotype in polar bears.
We also disagree that “damaging” is the right label to apply to these predictions in this context. This is a QUIRK of the program, that is being quote mined as a central claim in an important ID book. It all unravels on this quote mine.
In 1995 researchers knocked out (destroyed) one of the two copies of the APOB gene in a mouse model — the same gene as has been selected in polar bears. Although APOB is itself involved in the larger process of the transport of cholesterol, mice missing one copy of the APOB gene actually had lower plasma cholesterol levels than mice with two copies. (Mice missing both copies died before birth.) … Given the experimental results with mice, it is most parsimonious to think APOB is broken or blunted in polar bears . For mice, having only half as much APOB activity protects them from a high fat diet. For polar bears, having mutated APOB genes protects them from a high fat diet. If those polar bear mutations decreased the activity of APOB by half or more, then we might expect a similar protective effect as was seen in the mouse.
But I think next 4 or 5th polar bear seminar will be dedicated to this as well, so it is too early to say that DI has not responded, even if Behe responded personally, Yes, Behe likes to engage with Lenski on the same issue rather than with Nathan Lents, that is why he gets upset and claims that he has not responded to his point
Polar bears don’t have lower plasma cholesterol levels compared to brown bears. There doesn’t appear to be any significant difference between plasma cholesterol levels for the two species, higher or lower. Therefore, there is no phenotype consistent with a damaged APOB protein.
I care if Behe responds. Real scientists don’t point to anonymous posts from a non-scientific advocacy group to deal with critique. Behe knows this of course. As for me, I await his response. Of course, he likely has no response that he is willing to put his name on, so I’m happy to take it as a concession.