Some comments on this piece by @NLENTS.
I quote him in italics and my comments are in bold characters.
Presumably, polar bear APOB must be highly optimized for handling the high cholesterol burden.
This is a reasonable inference
Somehow, Behe draws the opposite conclusion
No, not really. What he said in DD is that the mutations in polar bear APOB were likely to be damaging. This is not incompatible with the notion that polar bear APOB must be highly optimized for handling the high cholesterol burden. Don’t forget that APOB is multifonctional, and, as a result, you can have damaging mutations affecting a particular function but not the others. In this situation, it is entirely possible that the resulting damaged APOB protein could be better for coping with high cholesterol burden.
This is puzzling because he notes that humans and mice with mutations that diminish the function of APOB are more prone to suffer heart disease
Agreed, this is kind of puzzling, for, as far as I can tell, it doesn’t seem to strengthen his case.
But polar bears do not get cholesterol-driven heart disease, so the logical inference to draw from these data is that polar bear APOB is enhanced , not diminished, by the mutations.
Given the functional complexity of APOB and our lack of knowledge regarding lipid metabolism in polar bear, I don’t think this conclusion is warranted.
Thus, the location of the APOB mutations provides more support that enhancement, not diminishment, has occurred.
In the case of a multifunctional protein such as APOB, this is untrue.
This program (polyphen-2) can predict whether a given mutation diminishes the function of a protein based on how closely it corresponds to human genetic variation that is known to cause pathology
As far as I can tell, this is incorrect, for PolyPhen-2 also relies on structural features to assess the possible diminishing effect of mutations