Lents and Hunt: Behe And The Polar Bear's Fat

[swamidass (S. Joshua Swamidass)]

Great article by @art and @NLENTS

Darwin Devolves: Behe Gets Polar Bear Evolution Very Wrong

https://www.sciencedirect.com/science/article/pii/S0092867414004887

Behe writes:

But what precisely did the changes in polar bear APOB do to it compared to that of other mammals? When the same gene is mutated in humans and mice, studies show it frequently leads to high levels of cholesterol and heart disease. The scientists who studied the polar bear’s genome detected multiple mutations in APOB. 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 the gene codes for.

And there’s more. If we come back to APOB, the polar bear gene that Behe spends the most time discussing, we find that the authors of the study have a very different interpretation of the data than Behe does. Quoting the paper again [emphasis added]:

Substantial work has been done on the functional significance of APOB mutations in other mammals. In humans and mice, genetic APOB variants associated with increased levels of apoB are also associated with unusually high plasma concentrations of cholesterol and LDL, which in turn contribute to hypercholesterolemia and heart disease in humans (Benn, 2009; Hegele, 2009). In contrast with brown bear, which has no fixed APOB mutations compared to the giant panda genome, we find nine fixed missense mutations in the polar bear (Figure 5A). Five of the nine cluster within the N-terminal ba1 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 .

Clearly, the authors do not expect the polar bear APOB to be “broken.” Rather, a bare majority of the amino acid changes are in the most important region for the clearing of cholesterol from the blood. In other words, these mutations likely enhance the function of apoB, at least when it comes to surviving on a diet high in saturated fats.

To recap: 1.) There is no evidence for Behe’s claim that APOB is degraded or diminished in polar bears and everything we know about the protein from other mammals suggests the opposite. And 2.) Behe’s claim that the most common adaptive changes in polar bears are those that degrade or destroy proteins is not supported, and the evidence suggests otherwise. Those are just the errors that we found in his first example.

And yet Behe makes this bold claim:

It seems, then, that the magnificent Ursus maritimus has adjusted to its harsh environment mainly by degrading genes its ancestors already possessed. Despite its impressive abilities, rather than evolving, it has adapted predominantly by devolving. What that portends for our conception of evolution is the principal topic of this book.

Behe’s Response

Behe responds here: Behe: Responding to the Polar Bear's Fat. Unfortunately, he doubles down on his mistake.

@swamidass

It is worth remembering that Behe’s response to the Polar Bear’s Fat created more problems. Behe: Responding to the Polar Bear’s Fat. This is his claim about ApoB:

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.

Two errors here:

1. They determined that the mutations were very likely to be damaging

The authors did not determine the mutations to be damaging. They ran a program that gave some results, and they (for a good reason) came to a different conclusion. On ApoB, one of the "damaged proteins, they write it is likely to be working more effectively. This make sense, because Polar Bears need a really effective ApoB because the eat so much fat.

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 .

2. damaging — that is, likely to degrade or destroy the function of the protein that the gene codes for.

In this context, the software program just outputs “damaging” if it is likely to be a function changing mutation. As a quirk of this program, it calls both increases and decreases in function “damaging.” It appears that Behe misunderstood how this program works. We expect many beneficial mutations to be called “damaging” by this software, but this does not mean that they are likely to degrade or destroy the function of the protein when applied to data like this.

Why this matters . It appears that Behe is working from an indefensible understanding of “damaging.” A keystone example from his publicly-available first chapter appears to be demonstrating quite different results than he expects and explains. This calls into question his whole argument.

That is on top of making a very misleading edit in his response:

This was just an unnecessary multiplication of existing error. What is in this table is beside the point.

@swamidass

[Behe] said the original authors concluded they were damaging. They did not. Full stop.

Very unfortunate.