A second highly selected gene, LYST, is associated with pigmentation, and changes in it are probably responsible for the blanching of the ancestors’ brown fur. Computer analysis for 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. Furthermore, since most altered genes bore several mutations, only three to six (depending on the method of estimation) out of seventeen genes were free of degrading changes [fn 2]. Put differently, 65 to 83 percent of helpful, positively selected genes are estimated to have suffered at least one damaging mutation.
- Darwin Devolves p. 21
fn 2 is Table S7 of Liu et al.
Can we work through this one item at a time to see what people agree with or disagree with?
I strongly doubt that, since you didn’t actually make a point.
I get the impression that Behe accepts that the attenuation of cholesterol levels is the likely mechanism by which mutations in APOB confer their adaptive benefit. From his book (pp. 16-17):
The only issue Behe cares about is about whether adaptation proceeds predominantly by the recruitment of mutations that degrade molecular function. In his latest piece, he is quite clear about his take-home message:
So what is at stake is whether the mutations break some molecular function or not.
Um. No. I challenge the reasoning, not the evidence.
X is evidence for common descent says dazz. Why does that count as evidence for common descent dazz? Handwaving begins …
Break or blunt.
So did you misrepresent Behe when you wrote:
I don’t think so. What makes you say that?
Clearly, the knock-out simply nukes all of the molecular functions of APOB, whereas the fixed mutations in polar bears were conspicuously clustered in the domain encoding the surface region which contains the majority of functional domains for lipid transport. Behe has been glossing over the fact that the protein needs to fulfill multiple distinct functions, which is a curious oversight given his preoccupation with the molecular details.
6 of one, half a dozen of the other. We still have no idea why you believe in common descent. You’ve been explained a thousand fucking times how common descent is inferred from the data and what’s the reasoning behind it. How many times have people linked to Theobald’s “29+ Evidences for Macroevolution” here at TSZ, ffs? Handwaving? What the hell are you talking about?
And yet you still can’t explain it and then blame me. Why don’t you start an OP and do something other than link to a page you’ve shown no evidence that you understand yourself?
That flies directly in the face of your characterization.
You make it sound like there was only one copy of the gene and that knocking it out destroyed all APOB function. That is not the case.
Do it formally. Or point to where it’s been done formally in such a way that you specifically stand by it. Or just whine on blogs the rest of your life. Take a stand. Start a blog. State your case in a single place that you can refer people to. Publish a paper. Or just whine on blogs the rest of your life.
There’s no reason “citizen scientists” can’t change the paradigm. No reason except being unwilling to even try.
Why would I want to do that? What would be the point when much smarter and much more knowledgeable guys here have already explained those things ad nauseam? I don’t mind admitting I only understand some of it (enough of it to justify my beliefs, I reckon) but at least I don’t think I’m making ridiculous, fundamental reasoning blunders like you do.
This is straight from Theobald’s piece:
Is that what you would call handwaiving when it comes to the reasoning behind what data counts as evidence for something and why? Give me a fucking break
That would be the implication, I guess, if and only if you are unaware that mice are diploid.
There’s a certain minimal level of competence that one assumes. In error, apparently. Sigh.
Still no-one is willing to check the bibliography for mouse ApoB references, huh?
Doesn’t appear to be a bibliography.
Great. You’re capable of copying and pasting. Soon you’ll able to do simple arithmetic. In a few more decades you may be capable of explaining the reasoning for your beliefs. But I’m not going to hold my breath.
0 matches found
Is that going to be the name of your first published paper?
Catchy title. Be interesting to see how the peer review process goes.
Would it kill you to be more specific???
You said it yourself you make predictions based on evolution…
Is there another kind of great care specifically for evolutionary predictions?
Is this the paper you have been so mystical about?
Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1774-8.
Knockout of the mouse apolipoprotein B gene results in embryonic lethality in homozygotes and protection against diet-induced hypercholesterolemia in heterozygotes.
Farese RV Jr1, Ruland SL, Flynn LM, Stokowski RP, Young SG.
Apolipoprotein B is synthesized by the intestine and the liver in mammals, where it serves as the main structural component in the formation of chylomicrons and very low density lipoproteins, respectively. Apolipoprotein B is also expressed in mammalian fetal membranes. To examine the consequences of apolipoprotein B deficiency in mice, we used gene targeting in mouse embryonic stem cells to generate mice containing an insertional disruption of the 5′ region of the apolipoprotein B gene. Mice that were heterozygous for the disrupted apolipoprotein B allele had an approximately 20% reduction in plasma cholesterol levels, markedly reduced plasma concentrations of the pre-beta and beta-migrating lipoproteins, and an approximately 70% reduction in plasma apolipoprotein B levels. When fed a diet rich in fat and cholesterol, heterozygous mice were protected from diet-induced hypercholesterolemia; these mice, which constitute an animal model for hypobetalipoproteinemia, should be useful for studying the effects of decreased apolipoprotein B expression on atherogenesis. The breeding of heterozygous mice yielded no viable homozygous apolipoprotein B knockout mice. Most homozygous embryos were resorbed by midgestation (before gestational day 11.5); several embryos that survived until later in gestation exhibited exencephalus. The embryonic lethal phenotype was rescued by complementation with a human apolipoprotein B transgene–i.e., human apolipoprotein B transgenic mice that were homozygous for the murine apolipoprotein B knockout mutation were viable. Our findings indicate that apolipoprotein B plays an essential role in mouse embryonic development.”
If yes, I have referred to it in my comments to Corneel reg embryo development in KO. Behe referred to it or similar studies with same results…
Boy! Can’t you even distinguish the mechanism from the effect of whatever that mechanism may be?!
The effect is atherosclerosis. The mechanism of its cause, or prevetion, is at issue here…whether it is high or low receptor affinity or another mechanism…
When you figure out the difference, let me know…
Thanks. That’s what I thought would be the case.
Here’s what it looks like from where I am.
Behe realizes, upon seeing the review in Science, that he made an unwarranted assumption about the nature of the mutations in Liu et al. There is, in fact, no reason to suppose that they are “damaging”. I will leave it to his fans to decide how damaging that discovery is to his thesis.
In an attempt to save face, he pulls up the Wikipedia page on ApoB and cites the observation from Farese 1995 that what Farese thinks is a knock-out mutation is embryonic lethal when homozygous, but the heterozygote appears protected from diet-induced hypercholesterolemia.
This appears to be the sum total extent of his research, used to sustain his thesis that “blunting or breaking” the ApoB gene is what allowed polar bears to adapt to a higher fat diet. I would like you to pause and consider the utter insanity of this position. Behe is hanging his hat, in what to all intents and purposes appears to be a post hoc Wikipedia-driven rationalization, on a single paper from 1995.
This is an immensely complicated field with thousands of publications. But Behe found a paper that is consistent with his position. That’s all the research he needs to do.
A couple of things amuse me.
1) Nobody would rely on the idea that an insertion into exon 4 was a null allele; Farese’s “knockout” produces the N-terminal portion of ApoB — it could easily cause weird results in the heterozygote. Abberant trafficking, perhaps?
Should I mention the tissue-specific RNA-editing that produces a truncated polypeptide? It’s right there in the Wikipedia article…
2) What is not in the wikipedia article is the other paper from 1995, from Huang et al (J Clin Invest. 1995 Nov;96(5):2152-61.).
THEY actually did the knock-out properly: they deleted the first three exons, and did back-crosses. They found similar embryonic lethality for the homozygote, but they did not see the weird resistance to diet-induced hypercholesterolemia that Farese saw and that Behe hung his hat on. Huang, with their more rigorous knock-out, saw neural tube closure defects, male infertility, and a major defect in HDL production in heterozygotes. That’s not going to be adaptive, kiddo.
What a shoddy piece of work.
Even okapidazz knows how to Google… so what’s your point, Jock?
I copied the abstract of FARESE you have been so keen to review with pictures of mice embryo knock outs…
Tell us the Darwin Devolves hidden killer you have found there…😉
You have typed all this in less than a minute??? 😉
Is this the Darwin Devolves revolver study, Jock?
“apo B gene knockout in mice results in embryonic lethality in homozygotes and neural tube defects, male infertility, and reduced HDL cholesterol ester and apo A-I transport rates in heterozygotes.
Huang LS1, Voyiaziakis E, Markenson DF, Sokol KA, Hayek T, Breslow JL.
apo B is a structural constituent of several classes of lipoprotein particles, including chylomicrons, VLDL, and LDL. To better understand the role of apo B in the body, we have used gene targeting in embryonic stem cells to create a null apo B allele in the mouse. Homozygous apo B deficiency led to embryonic lethality, with resorption of all embryos by gestational day 9. Heterozygotes showed an increased tendency to intrauterine death with some fetuses having incomplete neural tube closure and some live-born heterozygotes developing hydrocephalus. The majority of male heterozygotes were sterile, although the genitourinary system and sperm were grossly normal. Viable heterozygotes had normal triglycerides, but total, LDL, and HDL cholesterol levels were decreased by 37, 37, and 39%, respectively. Hepatic and intestinal apo B mRNA levels were decreased in heterozygotes, presumably contributing to the decreased LDL levels through decreased synthesis of apo B-containing lipoproteins. Kinetic studies indicated that heterozygotes had decreased transport rates of HDL cholesterol ester and apo A-I. As liver and intestinal apo A-I mRNA levels were unchanged, the mechanism for decreased apo A-I transport must be posttranscriptional. Heterozygotes also had normal cholesterol absorption and a normal response of the plasma lipoprotein pattern to chronic consumption of a high fat, high cholesterol, Western-type diet. In summary, we report a mouse model for apo B deficiency with several phenotypic features that were unexpected based on clinical studies of apo B-deficient humans, such as embryonic lethality in homozygotes and neural tube closure defects, male infertility, and a major defect in HDL production in heterozygotes. This model presents an opportunity to study the mechanisms underlying these phenotypic changes.”
ROFL, no J-Mac.
While I was typing, you were busy shooting yourself in the foot. My comment was a response to Mung, not you. And the reason I was asking about Farese, is because Behe cited it online, this week, to support his case. I was pretty sure that he was picking cherries out of his ass, but I needed one of you suckers who bought his book to confirm for me that there is no mention of Farese in the book, thereby confirming that it was a total ad hoc defense. While I was waiting, I discovered the awesome wikiepedia connection.
I read Farese the day that Behe first cited it. I also read Huang 1995: you should read it too: it is much more rigorous.
Your condescension is delightfully misplaced.
Good. You can cut and paste. Now try reading for comprehension, in particular the paragraph that begins “While this work was in preparation, Farese et al…”
I DIDN’T buy his book…you know… lol
Read my previous comment AGAIN about FARESE or similar studies….
Don’t jump into conclusions next time…😂🤣
I did not realize he had this special talent 🙂
Jock got into a sock… He had thought he set me up but he got too anxious and pulled the trigger too early and shot himself in the ass instead… 🤣
He is trying to recover from the “polar bear white fur coat” embarrassment… but he is not the only one…Behe scored so big on it, he didn’t even mention it in his last rebuttal to Lenski and the other less known musketeers…😂
Ah, OK. I see why it sounded like that to you. No, a complete gene knock-out* destroys all function of the product it encodes, but heterozygotes have the spare copy of course. Things got lost in translation I suppose. It doesn’t really affect my argument though.
* which apparantly it is not. That’s zealous, DNA_Jock.