Behe's response to Lenski's first post

Science

(Ashwin S) #1

Here is Behe’s second response to lenski’s first post in his review of Darwin Devolves.

Was waiting for somebody else to post. But since people seem to have missed it, I am posting the link.

https://evolutionnews.org/2019/03/for-dreams-of-darwinian-evolution-first-rule-of-adaptive-evolution-is-an-insuperable-problem/

If someone has already posted the link, then my apologies.


(S. Joshua Swamidass) #2

Thanks ashwins. Thankfully it looks like interesting is dying down on this. That was an intense few weeks.


(Ashwin S) #3

I guess Behe is going to post his rebuttals one by one in the coming days…
This might be just a lull in the discussion.


(Edgar Tamarian) #4

So, again Behe avoided evidence that challenged him?

As I noted earlier in after Behe’s first response to Lenski nobody could say anything substantial.
Behe summarizes his first response as follows.

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

Nobody said anything substantial to this.

Now, I am following, if anybody could show up and say a few sentences with substantial meaning about his second response to Lenski over frequency versus the importance of evolutionary changes.


(Arthur Hunt) #5

Here. Bottom line - Behe’s implications about APOB are unsupported and do not stand up to any sort of scrutiny.

Also, Behe ducks the matter of his misrepresentation of Liu et al.


(Edgar Tamarian) #6

In your previous post, there is no sentence-a sequence of words that says anything about

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

if you think there is, please copy past, the exact sentence one again here.


(Arthur Hunt) #7

It seems to me that Behe is now arguing that the putatively damaged APOB in polar bears lacks between 50 and 70% of the activity of its ortholog in brown bears (or maybe humans - it is not entirely clear from his use of the paper by Farese et al . just what the standard or control might be). Of course, he doesn’t offer any data to support this hypothesis, or otherwise argue that this explanation is better than that discussed by Lenski and Lents. But (good news, @Mercer) at least there is a hint of a testable hypothesis here. Regardless, APOB is still not the open-and-shut example Behe needs for his assertions to be correct.


(Ashwin S) #8

@Art
Can you share your views on Behe’s argument in the latest post?

I think it’s fairly clear that Behe’s assertions regarding APOB are yet to be proved. I don’t think Behe denies it himself. So your point is valid. And like you said, his hypothesis can be tested and hence falsified or verified. I guess we will have to wait till somebody does this before knowing for sure.


(Edgar Tamarian) #9

As Behe wrote

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. Given that computer analysis also estimated the APOB mutations in the polar bear as likely to be damaging, it is most reasonable to think the activity of the protein has been blunted by the mutations.

This is not data?, Behe clearly explained that clearance of cholesterol more efficiently is the result of deletion of one copy of the APOB gene in a mouse, which is good reason to think similar pattern happened in polar bears given also the computer program prediction.

  1. So what is your good reason to think otherwise,
  2. what is your positive data that mutated APOB gene in polar bears increased its activity, not decreased?

(Arthur Hunt) #10

So, @Edgar_Tamarian, you think a population of bears can persist if the males are seriously compromised for fertility?

Why did Behe not mention these findings? What is his explanation? Do you think he may start to sound more like Lents and Lenski when it comes to APOB?


(Arthur Hunt) #11

Hi @Ashwin_s,

Maybe later. I am curious to see if Lenski writes up something.


(Ashwin S) #12

Well we will wait it out then.


(Edgar Tamarian) #13

I really do not understand what is the connection APOB gene that is involved in fat metabolism with fertility

However, Behe wrote something interesting

Its [ APOB ] function is not “to help polar bears survive,” nor even “to clear cholesterol.” Rather, it has one or more lower level functions that are subservient to those higher purposes. Thus the fact that cholesterol might be cleared more efficiently in polar bears does not at all mean that APOB hasn’t been degraded, any more than breaking the off-switch of a shake machine so that it works continuously throughout lunch hour means some new improved function was added


(Arthur Hunt) #14

What you can or cannot understand is quite beside the point. The studies I linked to clearly show that APOB-deficient mice have male fertility defects. Behe should have mentioned this, as this observation tempers the notion that polar bears have only 50% of the APOB activity of brown bears.


(Edgar Tamarian) #15

You are wrong

in Farese et al it says

In contrast to our apo-B knockout mice, developmental abnormalities have not been observed in human apo-B deficiency syndromes. What could account for this apparent difference in the phenotypes of apo-B deficiency in mice and humans? One possible explanation relates to developmental differences between the two species. 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 that becomes an appendage attached near the allantoic mesoderm. Thus, it is possible that apo-B produced by the yolk sac in the mouse might play a more important role in facilitating the delivery of lipids or fat-soluble vitamins to the developing embryo early in gestation.

For the similar reason, it is not necessarily mean that decreased activity in APOB gene yields fertility defects.


(Arthur Hunt) #16

@Edgar_Tamarian, did you bother to read the two studies I linked to?


(Arthur Hunt) #17
  1. J Clin Invest. 1995 Nov;96(5):2152-61.

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 LS(1), Voyiaziakis E, Markenson DF, Sokol KA, Hayek T, Breslow JL.

Author information:
(1)Laboratory of Biochemical Genetics and Metabolism, Rockefeller University, New
York 10021, USA.

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.

DOI: 10.1172/JCI118269
PMCID: PMC185864
PMID: 7593600 [Indexed for MEDLINE]

  1. Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10903-7.

A novel functional role for apolipoprotein B in male infertility in heterozygous
apolipoprotein B knockout mice.

Huang LS(1), Voyiaziakis E, Chen HL, Rubin EM, Gordon JW.

Author information:
(1)Department of Medicine, Columbia University, College of Physicians and
Surgeons, New York, NY 10032, USA. lh99@columbia.edu

Male infertility, affecting as many as 10% of the adult population, is an
extremely prevalent disorder. In most cases, the cause of the condition is
unknown, and genetic factors that might affect male fertility, other than some
sequences on the Y chromosome, have not been identified. We report here that male
mice heterozygous for a targeted mutation of the apolipoprotein B (apo B) gene

exhibit severely compromised fertility. Sperm from these mice failed to fertilize
eggs both in vivo and in vitro. However, these sperm were able to fertilize eggs
once the zona pellucida was removed but displayed persistent abnormal binding to
the egg after fertilization. In vitro fertilization-related and other experiments
revealed reduced sperm motility, survival time, and sperm count also contributed
to the infertility phenotype. Recognition of the infertility phenotype led to the
identification of apo B mRNA in the testes and epididymides of normal mice, and
these transcripts were substantially reduced in the affected animals. Moreover,
when the genomic sequence encoding human apo B was introduced into these animals,
normal fertility was restored. These findings suggest that this genetic locus may
have an important impact on male fertility and identify a previously unrecognized
function for apo B.

PMCID: PMC38255
PMID: 8855280 [Indexed for MEDLINE]


(Edgar Tamarian) #18

You are NOT reading my post

in Farese et al it says

In contrast to our apo-B knockout mice, developmental abnormalities have not been observed in human apo-B deficiency syndromes . What could account for this apparent difference in the phenotypes of apo-B deficiency in mice and humans? One possible explanation relates to developmental differences between the two species. 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 that becomes an appendage attached near the allantoic mesoderm. Thus, it is possible that apo-B produced by the yolk sac in the mouse might play a more important role in facilitating the delivery of lipids or fat-soluble vitamins to the developing embryo early in gestation.

For a similar reason, it is not necessarily mean that decreased activity in APOB gene yields fertility defects.

Otherwise, you have to show that in polar bears the yolk sac plays the same developmental role as in mice.


(S. Joshua Swamidass) #19

Well, you are not reading mine. Where did Behe address this?

Where did Behe address this? I have not found out where he justified this representation of the author’s conclusions.

Where has he addressed this? I have not yet seen it?

We responded in detail to every point Behe has raised. Often we had answered him before he even made the objection. We are just asking for the same courtesy.

@Edgar_Tamarian, it seems that the squid ink from ENV is successfully confused and disoriented you. This does not take scientific expertise to understand.

  1. Behe did not correctly represent the views of the author’s of the study.
  2. When this was pointed out, he called us incompetent.
  3. He never dealt with this fundamental critique.

Instead, he ignored our point, and jumped when to arguing he was correct.

  1. To his credit, he did add new information (not into his book) that raises questions about a simplistic answer, but creates another scientific problem for him

I do not expect you to grasp #4, but #1-#3 are straightforward. He has not responded.


(S. Joshua Swamidass) #20

I’m not surprised a close read of those papers shows he left an important fact out. @Art, would you like to write up an explanation of the dialogue with me that doesn’t respond to Behe as much explain the exchange to observers in an engaging way? I think this will be fun, and would want to coauthor it with. I know @Nlents is getting tired of Behe, but if we focus this on explaining how biological reasoning works to the public, that could a broader approach.

What do you think?