Reaping the Whirlwind: protein function without stable structure


(Raymond Isbell) #423

Just means “all other things being equal.” I got sick of hearing it in my Economics classes. But it’s an important concept. In complex systems where there’s lots of interdependency, all other things are usually not equal. So when you said “None of them deal with changes in expression due to methylation.” I wondered if methylation was the only way gene expression is modulated. Not being a biologist, I don’t know that much. I’ve read a little about gene regulatory networks and recall the following form Meyer’s book “Darwin’s Doubt” Here’s the quote:

When they proposed their theory in 1969, Britten and Davidson acknowledged that “little is known . . . of the molecular mechanisms by which gene expression is controlled in differentiated cells.”24 (Britten and Davidson, "Gene Regulation for Higher Cells, " 57.) Nevertheless, they deduced that such a system must be at work. Given: (1) that tens or hundreds of specialized cell types arise during the development of animals, and (2) that each cell contains the same genome, they reasoned (3) that some control system must determine which genes are expressed in different cells at different times to ensure the differentiation of different cell types from each other—some system-wide regulatory logic must oversee and coordinate the expression of the genome. Note - 25 (Britten and Davidson, "Gene Regulation for Higher Cells, " 353.)

Sounds like the GRN’s also change gene expression. Thus, my question, “All other things being equal.” What I was really driving at is the question, "Is methylation the only way to change gene expression? If not, then all other things may not be equal. Isn’t that what epigenetics is about, viz. changes in gene expression from outside influence? Is methylation the only cause?


(Dennis Venema) #424

How cells take on different functions during development (and express a certain subset of the genes within the genome) is not epigenetics - it’s developmental biology (though epigenetics adds some minor variation to the process). A major mechanism is asymmetric cell division that divides regulatory proteins into different cells, giving them different subsets of proteins that then go on to regulate other genes (i.e. express them), which are then asymmetrically divided, and so on.

This all runs backwards to the asymmetry found in a fertilized oocyte - and a major determinant of the first asymmetry there is the point of sperm entry.

So, we know a lot about how gene regulatory networks work.


#425

@Raymond_Isbell Meyer is using a paper from 1969 in a book written in 2014? A 45 year old paper in a field that is rapidly changing. Not having the book myself, do you think maybe Meyer was just looking for a good quote for his book with no regard to what may currently be known?


(Chris Falter) #426

To elaborate a bit on Dennis’ excellent explanation, the substantial changes in gene regulatory networks identified in the papers were all changes in nucleotide sequence. Methylation of gene regulatory networks can yield short-term changes in gene expression and are referred to as epigenetic changes. But the peer-reviewed research identified non-epigenetic changes–i.e., changes in nucleotide sequence.


(Dennis Venema) #427

Indeed. GRNs are robust to single nucleotide changes over time within a lineage, and to mixing and matching of different alleles through sexual recombination.


(Raymond Isbell) #428

I’m puzzled at why you challenge this unless you know it’s wrong. Is it wrong? Remember that the goal we have (or at least me) is to determine which is the better explanation of the data, evolution or design. Why would you challenge a book that you haven’t read? Is it possible that he may have had a good reason to have included that reference? Getting to the truth on an issue requires that one examine both sides with an open mind and withholding conclusions until the data is in, analysis is completed, and both sides are heard. Am I wrong? When one side adopts your style of argument, it arouses suspicion.

This stuff is complex and difficult to understand. Coming to a conclusion on which side is correct requires patience, discipline and a willingness to be open minded. Condemning an argument because it’s citing an old source may be correct if that old source has been replaced and shown to be wrong. However, if the old source is still correct, I would read that argument carefully and completely to see if there was a good reason for including it. Perhaps he is stressing the point that not only is it true, but it has been known to be true for a long time? Thoughts?


#429

@Raymond_Isbell The problem is when an ID author quotes a paper simply to cast doubt on the theory of evolution. It is a consistent pattern that I have seen. And when a very old paper is used when much more is now known about GRN, just do a Google Scholar search, the reality is the author is being dishonest.

The quote is

Yes it was true that “little is known” but that was in 1969. It isn’t true today as Dennis and Chris point out. Do you still think the quote is a good use of the content of that particular paper?

And one more point, when I see the ellipses in a quote I suspect something important might have been left out. In this case that didn’t happen. I found the quote is on the page you can see here Read it and see what you think of Meyer’s use.


(Stephen Matheson) #430

Hi Bill, the quote is from a section of the book (Darwin’s Doubt) in which Meyer is introducing the whole concept of GRNs. In that section he is highlighting Davidson’s ideas. The book is pretty worthless overall, but this section is rather nice and the historical reference to the Britten-Davidson model is fine. You are justified in suspecting quote mining, but in this case Meyer is not doing that, and is instead noting that Britten & Davidson were proposing a model of gene expression regulation before much was known about the topic in animals. Of course, a Nobel had already been awarded, 4 years before, for work on the lac operon, so the notion of DNA-based control switches was already established. But the quote from Meyer is not inherently misleading or problematic, IMO.


(Raymond Isbell) #431

Casting doubt on the theory of evolution (macro that is) is exactly what he’s doing. He believes it is wrong, and is making an honest attempt to present his reasoning. Are you saying that he should not challenge evolution? If evolution is wrong, then his action is justified, maybe even noble. Would it be a good thing to talk someone down from jumping off a tall building? For our discussion, Meyer’s motives are not the issue. His hypothesis and reasoning are.

I would think that the issue before us is the explanatory power of design vs. evolution. That’s certainly my goal. I’m listening to both sides, and I won’t condemn either side until I have looked at their reasoning carefully. Meyer is presenting an argument that shows the evolution argument requires embracing things that are highly unlikely. Is it wrong to point that out? Meyer is trying to convey the notion that random changes to the whole network of interactive signaling molecules is more likely to be destructive than beneficial. Since you haven’t read the book, here’s a quote from pg 264-5 in “Darwin’s Doubt” that shows his point: (emphasis is mine)

Another line of research in developmental biology has revealed a related challenge to the creative power of the neo-Darwinian mechanism. Developmental biologists have discovered that many gene products (proteins and RNAs) needed for the development of specific animal body plans transmit signals that influence the way individual cells develop and differentiate themselves. Additionally, these signals affect how cells are organized and interact with each other during embryological development. These signaling molecules influence each other to form circuits or networks of coordinated interaction, much like integrated circuits on a circuit board. For example, exactly when a signaling molecule gets transmitted often depends upon when a signal from another molecule is received, which in turn affects the transmission of still others—all of which are coordinated and integrated to perform specific time-critical functions. The coordination and integration of these signaling molecules in cells ensures the proper differentiation and organization of distinct cell types during the development of an animal body plan. Consequently, just as mutating an individual regulatory gene early in the development of an animal will inevitably shut down development, so too will mutations or alterations in the whole network of interacting signaling molecules destroy a developing embryo.

Meyer, Stephen C… Darwin’s Doubt (pp. 264-265). HarperOne. Kindle Edition.

The reason I find Meyer’s argument appealing is that it’s consistent with my assertions about Systems Engineering principles. INCOSE calls it “rich interdependence.” If a random change to a nucleotide happens which affects the protein specified by it, and there are many other proteins that depend on the one that changed for their correct function, they may fail unless the change is non-critical or all the other dependent proteins are insensitive to random changes to others. You claim that the cell is robust enough so that that change is tolerated, and you claim that testing has demonstrated it. How many proteins are there, and how many have been tested? Has the testing included all possible nucleotide changes and determined that all proteins are robust to all changes? Or are there certain nucleotide positions that are more critical and thus cause the corresponding protein function to be more sensitive? If the latter, does Meyer have a point? Have all protein coding genes been tested? If not, is it reasonable to generalize the results of those you have tested to conclude that all proteins are robust and insensitive to random nucleotide changes?

I think Meyer has some good points that are not being answered by evolutionists like yourself. Instead of giving carefully reasoned responses, you just dismiss them as Meyer’s deceitful attempts to trash evolution.

You claim this recent example regarding Davidson’s work is an example of bad tactics from the ID folks. I read your excerpt from Davidson’s paper and see nothing wrong with Meyer’s quote of it. Maybe I’m missing something. You’ll have to explain it if I did.


(Raymond Isbell) #432

Apparently Evolution News just published this article this morning. Seems relevant to our current discussion.

Enjoy.

https://evolutionnews.org/2019/02/at-last-the-details-of-how-proteins-evolve/


#433

First I am a layperson in this discussion so all of your references to “you” are incorrect.

As I said initially I don’t have access to the book so I couldn’t see the context in which the quote was used. If you remember I asked you if this was a good use of the quote. While Stephen doesn’t consider it a quote mine to me it still smells like one. Like I said earlier there are so many quote mines that there is an online list.

It is hard to give a carefully reasoned response to a book I haven’t read. I have limited time for this hobby and am selective in what I read. Others have done a good job of pointing out the problems with the book.


(Chris Falter) #434

The author of the blog post, Cornelius Hunter, is answering questions at the Peaceful Science forum:


(James McKay) #435

One question here.

Exactly what doubt is he casting on the theory of evolution? More to the point, exactly which aspects of the theory of evolution is he casting doubt on?

Is he questioning:

  1. whether the earth is 4.5 billion years old?
  2. whether humans and apes share a common ancestor?
  3. whether mutations can add new information?
  4. whether life can come from non-life?
  5. merely whether evolution is some kind of Grand Unified Theory Of Everything that could do away with the idea of a Creator altogether?

Here’s the problem. Most ID proponents such as Behe, Meyer, and so on, only question (3), (4) or (5). I’m pretty sure that Michael Behe acknowledges universal common ancestry, for example: if I’ve understood him correctly, he only believes that the theory of evolution is incomplete; not that it is incorrect. Certainly, the Scientific Dissent from Darwin allows for such views with the way that it is worded.

However, many lay Christians, when they hear ID proponents talking about “Darwinism” or “evolution”, will assume that they’re talking about all five of the above. They will see the Discovery Institute proclaiming that a thousand scientists have signed the Dissent from Darwin, and will therefore assume that that means there are a thousand scientists who believe that the earth is only six thousand years old, or that humans and apes are unrelated. When most of the thousand scientists in question believe no such thing.

This is my main gripe about ID proponents. They really need to stop using the word “Darwinism,” for the simple reason that it is a weasel word. Instead, they need to state clearly and unambiguously, exactly which aspects of the theory of evolution they disagree with, and why. Because anything else is simply not honest.


(Raymond Isbell) #436

This last post by James asks some good questions. I’m composing an answer and it’s challenging. I want to give him a thoughtful answer so I’m going back and re-reading some of our posts and reading some of the references provided by those of you who are attempting to inform me on both evolution and biology. It’s good reading. I’ve spend a good part of yesterday and today reading, thinking and writing. I’ve reached a point today where my brain is spelling “TILT” in bright colors. I will continue and hope to get something out tomorrow that will respond to James.


(Randy) #437

Best wishes! What does “TILT” mean? :slight_smile:


(Phil) #438

Pinball reference for us old folks


(Stephen Matheson) #439

He might be using the term in its poker context, but for me, tilt will always be pinball.

How do you think he does it? I don’t know!
What makes him so good?’

He ain’t got no distractions
Can’t hear those buzzers and bells,
Don’t see lights a flashin’
Plays by sense of smell.
Always has a replay,
‘N’ never tilts at all
That deaf dumb and blind kid
Sure plays a mean pinball.


(Randy) #440

Interesting! Thanks. So if one “tilts” at pinball, (I’m looking this up)–it means that the pinball machine shuts down because someone is tilting it? So–this means that there’s overload and he’s shutting down for the night :). Got it. I probably get that enough. I learn all sorts of things on a science discourse.


Tilt
The tilt mechanism detects when the machine is being lifted, tilted or shaken beyond an acceptable level. Originally designed to prevent players from lifting the front of the machine to cause balls to roll backwards, it also helps prevent damage to the machine’s hardware, body and legs by discouraging players from shaking the machine too hard. When the mechanism is triggered, the machine “tilts”, ending play for the current ball and usually forfeiting any bonuses earned. Most modern games provide a configurable number of warnings per ball before tilting. Some older games would void the entire game upon tilt.


(Raymond Isbell) #441

Remember the old cartoons of yesteryear when something has reached a limit and falls over and crashes. TILT as in tilted and about to fall?


(Randy) #442

No, but I grew up in Africa and we didn’t get much in the way of TV, period :slight_smile:

Fun to learn–

but the Elton John reminded me of how one of my roommates in med school loved his music :). Neat pictures of the glasses.