Detwiler: Questions Behe, Polyphen, and Ratchets


(John Detwiler) #102

That’s true, but completely separating them also leads to confusion if one concedes that a minimal amount of structure is required for function.

You say “the basis” like there is just one. If you have a really good “theory of everything” that harmonizes all the factors we know about in this context, I think it would be fascinating to hear.

(John Detwiler) #103

In their maximum likelihood comparisons they examine endosymbionts from both humans, gorillas, tsetse flies, pigs, cows, nematodes, etc… Due to the genetic similarities between these lice, they assume that these lice were not created at the time that their hosts were created and they also assume their hosts evolved millions of year ago. It’s a valid argument, but not necessarily sound if these assumptions are wrong. If these hosts were created with lice specialized for each association, then assuming ancient rates of substitution from a formula can obviously be done, but would be pointless. You would only do that if you assumed they weren’t created. That’s why question begging is fallacious.

(Mikkel R.) #104

Ahh, so you base this belief of yours primarily on a hunch. Well allow me to not take your arguments seriously then.

But Behe’s rule is not about the rate of deleterious vs beneficial or neutral mutations. If anything, Behe’s rule seems to say that natural selection has no issue increasing relative fitness of an organism. The polar bear adapted to it’s environment, and it’s ancestors were brown bears that adapted to their environment before them.

Because it seems that every day new disease causing mutations are arising, but we aren’t getting anywhere close to that number of new beneficial proteins found.

That makes no sense. You seem to be insinuating that for every disease-causing mutation, there should be a novel beneficial entire protein to counter it.

Because of the fine tuned nature of protein protein interactions and the types of machines they produce. I think a lot of people imagine that building machines is easy if they never try.

The appeal to “how easy it is to a human” fallacy. Where have I heard this one before?

So you accept it is a reality that agriculture and medical science is counteracting natural selection in the human population to a certain extent. Then all the more reason for you to agree that you can’t extrapolate the situation in the human population to any long-term trend in the biosphere as a whole.

(Mikkel R.) #105

Then your belief is in error. Will you correct that belief?

But creationists don’t require that organisms always have a minimal amount of “value” or “fitness” below which they must die. I think everyone here agrees that negative selection does not always instantly kill an organism.

Nobody here requires that.

When people talk about “neutral” mutations and traits, they are talking about selective advantage at that moment. I’m trying to get at what may be a moving baseline in protein stability which would have far less impact at the moment as long as everything still folds.

I can barely make sense of this. What is “a moving baseline in protein stability”?

(Mikkel R.) #106

I’m sorry but this is wrong. It is not assumed that “lice were not created at the time that their hosts were created”, that is an evidentially derived conclusion. It is the ability of models to account for the patterns in data with superior parsimony and explanatory power compared to other models, that is evidence that in fact these species all share common descent. It is not assumed.

and they also assume their hosts evolved millions of year ago.

Again, that is an evidentially derived conclusion, not an assumption.

It’s a valid argument, but not necessarily sound if these assumptions are wrong. If these hosts were created with lice specialized for each association

What evidence do you have that they were?

(John Mercer) #107

Why would I concede that, when there are cases in which unstructured proteins (or domains of proteins) are required for function?

My mistake. I should have written the plural “bases.”

(John Detwiler) #108

but ones that are persisting despite negative selection. Yes, we’re discussing SNPs here. I’m trying to investigate if the reason that even evolutionists claim that 99.9% of all species that ever lived are extinct might one day become 100% I’m trying to investigate if the amount of relative advantage gained by slight changes to a gene can overcome what seems to be gradual losses of fitness in nearly all genes. I understand you are claiming that you believe negative selection will be able to purge them efficiently, but I haven’t seen anything convincing.

This seems to answer the converse, so we would share the rest. Near the beginning they put the figure at 22,000 so they are talking about protein coding genes.

“These changes account for the gain of 689 genes and the loss of 86 genes from the human genome. Over the same time period, chimpanzees have experienced expansions in 25 families (26 genes) and contractions in 546 families (729 genes).”

(John Detwiler) #109

I’m glad you used the term relative fitness. I’m trying to see if there’s a way to evaluate what might be more absolute fitness - fitness in regards to the rest of the biosphere, not just one’s own species.

I think a fair comparison would be to a duplicated protein that gains some different function or repairs a previously damaged function. I didn’t mean to insinuate it had to be a de novo protein.

Right, I’m saying it’s a fallacy. My point is that the electrostatic surfaces of proteins seem to be very precise. Most evolutionists seem to feel that if the sequence or fold is there, that splicing and control regions will just throw together the machinery given enough time. I’m saying THEY base it off the fallacy that humans don’t seem to have a problem doing it.

Only in the size of the population. I don’t believe humans were created with a minimum level of absolute fitness. I think there was probably a good bit to spare. I have a notion that the decline in lifespan in Genesis reflects the inability of heavily inbred offspring to retain the level of genetic diversity in Adam and Eve.

(John Mercer) #110

I’m not.

I’m discussing newly-discovered, disease-causing mutations. The question that followed it was not a reference to SNPs, but the concept of polymorphism. Are you familiar with it?

You seem to be doing more pontificating and false attribution than investigating.

How do you “understand” that? Precisely what did I write that led you to conclude that I believe that?

It seems to me that you only see what you want to see.

(John Mercer) #111

Why does it seem to be that way? What does that even mean?

Do you think that falsely attributing a position to a group of people is ethical? Can you quote a scientist saying that?

How is “sequence” synonymous with “fold”?

I’m saying that YOU are making stuff up.

(Dave Carlson) #112

That would still be a form of relative fitness.

(John Detwiler) #113

I think Dan has stated many times that a code is not functional unless it is under selection. He doesn’t make teleological judgments about functions like others are tempted to. He does have a certain internal consistency there. So if a code reproduces, what do you think Dan believes is lost?

My idea is that if proteins (especially medium to larger ones) are as hard to find from random sequences as they are, and that if such small substitutions down to even one residue have like a 30% chance of denaturing the entire protein, that any mutations not included in the initial genetic diversity in the first populations created would be expected to at least reduce the thermal stability of the proteins they occur in. Obviously if they break vital proteins, we will have no record of those. But it seems that even if they don’t, I would expect to find evidence of them on average destabilizing a protein rather than stabilizing it further. I could be wrong, but I’m interested in finding a way to test it. Obviously I would have to find a way to either estimate initial diversity, or else just repeatedly compare genomes of parents and children and test that instead seeing as back mutations would be expected to be almost non existent probability wise.

(John Detwiler) #114

I’m not denying there is evidence for their premises. In fact I think there’s great evidence for evolution. I just think there’s also great evidence for creation as well. I want to have the best arguments for both sides. Choosing the premise they did automatically rules out special creation. That is fine for many internal arguments. But if someone is questioning the basis for that evidence itself, as these discussions do, proving internal consistency is pointless.

Mountains! No true scientist claims otherwise! But seriously, when a person begins to assimilate thousands and thousands of observations about something as complex as proteins and the explanations for life, it can only end up being handled as a notion. So if you can read it generously, my notion, which I’m working back from to search out specifics, stems mainly from protein structures and their interactions and mechanisms. Their level of precision in recognizing electrostatic patterns seems extreme and extremely sensitive to perturbation. Their level of internal “integration” in terms of each members contribution to the position of others and the active sites seems equally extreme. The hierarchy in which they are controlled, and the interdepencies of their functions with eachother would seem to multiply the probabilities of their ever being found randomly by countless orders of magnitude. The VP40 gene in ebola is a great example of this. I has 3 distinct formations that all found targets in an environment of just 7 genes. It’s basically enough evidence to make me question alternatives, and not just assume a maximum likelihood because “other organisms have it too”. I have no doubt that larger population sizes slow down Muller’s ratchet. In fact, I have a notion that bacteria may be able to overcome it entirely although I have my doubts.

(John Detwiler) #115

I guess you would only be forced to concede it if you did a study on how often a previously folded protein fell apart and was then selected for how great its new function was. Maybe you could get lucky and that string of amino acids will wrap around some other useless protein and BAM!, a suped up ribosome! I can’t deny it’s possible!

Yes. I think it was more common when people just talked about “alleles” and “traits” instead of the underlying mechanisms. But what are you ideas?

I probably just painted you with a broad brush. Please accept my apologies. It’s been quite a long thread, and I don’t know of an efficient way to view it. Does this mean you doubt negative selection can effectively purge them then?

(John Detwiler) #116

The surfaces of many proteins so precisely match their close negative pattern on another, that the bonds formed are enough to form a complex as if the two (or often many many more) act as one giant protein. So instead of the difficulty of hoping this or that different amino acid will keep one smaller protein together, in the case of these constructs, sometimes an entire side has to match with enough fidelity for the entire thing to be stable.

Inordinately they find matching patterns on themselves which I have yet to find a good explanation for since most evolutionary explanations for proteins is that they get lucky with a site already existing in a network.

I think that gene duplication and recombination is pretty much the usual escape hatch isn’t it? I’ve read countless papers that leave it at that. Find me a white swan sir. mmmm Nah.

False attribution! If you look carefully, you’ll see I used the word “or”.

(John Mercer) #117

They don’t. Where did you get that idea?

You’re ignoring the data I showed you again.

No. That is very far from reality. You’re still conflating folding and function.

I don’t think so and I don’t think you’re familiar with it. Talking about alleles and traits in no way excludes talking about the underlying mechanisms.

Wouldn’t that depend almost entirely on whether they are dominant or recessive? Do your notions include the concept of diploidy?

(John Mercer) #118

No, they don’t “precisely match.” Proteins are flexible (about the consistency of a rubber ducky) and very sticky. If you look at any crystal structure, many parts are solvent molecules. Do you know what that means?


Nope. Given your lack of basic understanding, I’m pretty certain that you ignore any data that might make you reconsider any of your notions.

You’re saying the same thing about both sequences and folds, aren’t you? It simply doesn’t make sense as a blanket claim covering both.

(John Detwiler) #119

This is technically true. I should have said in regards to the physical interactions between atoms. But I would imagine that in terms of the environmental resources and dangers in a niche, there are myriad, nearly identical sources for them to a level that it is almost to the same effect be it somewhat noisier. Right now I’m just wondering about thermal stability, which would be more hidden from the biosphere (again not entirely), but not basic physics.

(John Mercer) #120

Then why did you blow off the thermal stability data I provided? Eight (sometimes dominant-lethal) mutants, all more thermally stable than wild-type. How can that be if your notions have any relevance to the real world?

(John Detwiler) #121

because I have no problem believing there are plenty of bad mutations that are more thermally stable. I’m looking for mutations in a child that aren’t in the parent that are neutral or especially beneficial that are more stable and to characterize how often something like that occurs. Why would the data you provided be relevant to that?