Genetics and Genesis

[gluadys]

You guys are confused by the terms mutation, transcription error and now bottlenecks and gene flow.

No we are not confused. We suspect that you are and are trying to determine whether or not that is the case. Don't assume that because someone asks a question they don't already know the answer.

Btw, you haven't explained "gene flow" yet.

A population bottleneck (or genetic bottleneck) is an evolutionary event in which a significant percentage of a population or species is killed or otherwise prevented from reproducing, and the population is reduced by 50% or more, often by several orders of magnitude.

Population bottlenecks increase genetic drift, as the rate of drift is inversely proportional to the population size. They also increase inbreeding due to the reduced pool of possible mates (see small population size).​

http://en.wikipedia.org/wiki/Population_bottleneck


It's easy to cut and paste a definition. That doesn't mean you understand the concept or use it correctly. Let's go back to the remark that prompted these questions:

Just think about it for a minute, does their common ancestor really have time for the accumulation of missense mutations to start having a beneficial effect? For one thing the deleterious effects will manifest and there will be a restriction of gene flow from a bottleneck in order for them to be fixed.

Since you haven't yet defined gene flow, define it now, and then explain why there would be a restriction of gene flow from a bottleneck.

Also, why would there be a bottleneck at all? Defects traceable to mutational causes do not ordinarily produce a population bottleneck. Why are you assuming such would be the case?

Now you are asking about what I expect to learn about adaptive evolution from molecular mechanisms that produce adaptive traits.

Give me a break...

Why should I give you a break? You keep asking for a molecular mechanism, but you have given darn little information about what "molecular mechanism" means to you. What would a molecular mechanism have to show for you to be convinced that adaptive evolution has happened? Be specific and detailed please.

 

[Xaero]

How mutations happen is not important for this discussion, we know that that they happen. They cause "noise" in the genetic information and out of this noise come beneficial or deleterious traits which get sorted out by selection pressure.
This is the big picture: through genetics we see that we share common ancestry, but we do not know every single step.

But we are advancing more and more on how mutations in certain genes enhances or degrades metabolic functions. So there are beneficial mutations. There are tons of them, but Yecs won't accept them because they want to see a dog that breeds a cat or something like a squirrel giving birth to a monkeyfrog


btw, transcription is copying genetic information from DNA to RNA. Errors while transcription normally won't get inherited (except retroelements) . Errors while replication/repair of germ-cell DNA are the mutations that get inherited.

 

[shernren]

I think I know what your problem is, you don't understand basic biology. You don't know what transcription is even though the central dogma of biology has been DNA-transcription-RNA-translation since Watson and Crick demonstrated the structure of the double helix.
...
You have made two gross fundamental errors and have yet to realize it. You have completely abandoned the evidence and the proper use of basic biological terminology so there is no basis for proving or disproving anything to you.

I have seen evolutionist arguments implode before but this one is a classic case of begging the burden of proof on your hands and knees.

Unbelievable...

This is utterly hilarious. Look at your own definition of transcription: DNA -> transcription -> RNA -> translation. Now, a mutation is a change in DNA that is passed on to subsequent descendants of that cell line (or die with the cell when apoptosis occurs).

Transcription is a DNA -> RNA process.
Mutations are DNA -> DNA processes.

So why exactly would transcription errors have anything to do with mutations? You have been saying that transcription errors are mutations for a long time now (for example here) and every time you do, you demonstrate a basic misunderstanding of genetics. There is exactly one very limited case in which a transcription error actually has anything to do with mutations. Because of the context, it has nothing to do with what we are discussing.

 

[Xaero]

Transcription is a DNA -> RNA process.
Mutations are DNA -> DNA processes.

Like i've said, mutations caused by Retrotranposons can also consist of transcription errors because they transcript from DNA to RNA and then back to DNA (this is while it's called "Retro").
So Mark isn't totally wrong with this, but normally point mutations are caused by errors in DNA repair. (i.e. fixing double strand break or an error during replication)

 

[shernren]

Like i've said, mutations caused by Retrotranposons can also consist of transcription errors because they transcript from DNA to RNA and then back to DNA (this is while it's called "Retro").
So Mark isn't totally wrong with this, but normally point mutations are caused by errors in DNA repair. (i.e. fixing double strand break or an error during replication)

Yeah, that's the "one very limited case" I was referring to. But Mark is always emphasizing (or trying to emphasize) neural genes, and I don't see how retrotransposition errors would have anything to do with them.

 

[mark kennedy]

Like i've said, mutations caused by Retrotranposons can also consist of transcription errors because they transcript from DNA to RNA and then back to DNA (this is while it's called "Retro").
So Mark isn't totally wrong with this, but normally point mutations are caused by errors in DNA repair. (i.e. fixing double strand break or an error during replication)

I'm not totally wrong? He can't recognize that a mutation most often is a transcript error and flagrantly denies that it is, in fact he didn't recognize the DNA - Transcription - RNA- Translation and despite elaborate expositions of the ASPM paper he says this.

I don't see how retrotransposition errors would have anything to do with them.

He has argued furiously that mutations are not the result of transcript errors and scoffed at the central dogma of Biology as described and demonstrated by Watson and Crick. Is it any wonder that he does not realize that the differences between the chimpanzee and human protein coding gene in question are either the result of mutations or independent creation.

He makes repeated fundamental errors I correct with some of the most basic Biology available and I'm not entirely wrong?

Did you read the paper?

AMONG mammals, humans have an exceptionally big brain relative to their body size. For example, in comparison with chimpanzees, the brain weight of humans is 250% greater while the body is only 20% heavier. The dramatic evolutionary expansion of the human brain started from an average brain weight of 400–450 g 2–2.5 million years (MY) ago and ended with a weight of 1350–1450 g 0.2–0.4 MY ago. This process represents one of the most rapid morphological changes in evolution.( Evolution of the Human ASPM Gene, a Major Determinant of Brain Size, Genetics 2003)​

The point mutation rate in the ASPM gene that spans 62 kilo bases encoding a protein 3477 amino acids long was estimated at 1 x 10-9/site/year based on a genomic comparison between humans and chimpanzees.

Human ASPM has 28 coding exons, spanning 62 kb encoding a huge protein of 3477 amino acids. I assumed that all indels with sizes that are multiples of three nucleotides do not disrupt an ORF. It would have required a point mutation rate of 1 x 10-9/site/year, which was estimated from a genomic comparison between humans and chimpanzees. the total 1019 indels are of sizes that are assumed to be in multiples of three nucleotides since an open reading frame (ORF) is interrupted when an indel of a size that is not a multiple of three nucleotides or a nonsense point mutation occurs. (Evolution of the Human ASPM Gene, a Major Determinant of Brain Size, Genetics 2003)​

Does that mutation rate seem a little high to you for a neural gene, it seems a little high to me. You ought to check it out some time, they have no clue what the molecular mechanism was that produced the positive evolution that would have had to produce the most dramatic adaptation in evolution.

 

[Xaero]

a mutation most often is a transcript error

Wrong. An error while transcription don't alter DNA.

The erronous transcribed RNA only produces a different protein (or just nothing) for one time. Such errors won't get inherited.

scoffed at the central dogma of Biology

i can't find where he did this.

He makes repeated fundamental errors I correct with some of the most basic Biology available and I'm not entirely wrong?

Your usage of the term "transcription" wasn't appopriate.
In post #52 you quoted 2 examples when mutations happen: during DNA replication and DNA repair, no word about "transcription".

But i see in post #57 that you now got it right.


Here is a list of correct terms:

DNA to RNA: transcription
RNA to DNA: retrotranscription
DNA to DNA: replication
DNA/RNA to Protein: expression
Protein->DNA: (still in development and only in labs)

Does that mutation rate seem a little high to you for a neural gene, it seems a little high to me. You ought to check it out some time, they have no clue what the molecular mechanism was that produced the positive evolution that would have had to produce the most dramatic adaptation in evolution.

AFAIR the mutation rate got lower during evolution in the human lineage - I will check some more ASPM papers the next days ...

 

[shernren]

I'm not totally wrong? He can't recognize that a mutation most often is a transcript error and flagrantly denies that it is, in fact he didn't recognize the DNA - Transcription - RNA- Translation and despite elaborate expositions of the ASPM paper he says this.

You've got to be kidding!

Transcription is a DNA -> RNA process.

What is a mutation, mark? Does it change DNA? Or does it change RNA?

 

[sfs]

The point mutation rate in the ASPM gene that spans 62 kilo bases encoding a protein 3477 amino acids long was estimated at 1 x 10-9/site/year based on a genomic comparison between humans and chimpanzees.

Human ASPM has 28 coding exons, spanning 62 kb encoding a huge protein of 3477 amino acids. I assumed that all indels with sizes that are multiples of three nucleotides do not disrupt an ORF. It would have required a point mutation rate of 1 x 10-9/site/year, which was estimated from a genomic comparison between humans and chimpanzees. the total 1019 indels are of sizes that are assumed to be in multiples of three nucleotides since an open reading frame (ORF) is interrupted when an indel of a size that is not a multiple of three nucleotides or a nonsense point mutation occurs. (Evolution of the Human ASPM Gene, a Major Determinant of Brain Size, Genetics 2003)​

Does that mutation rate seem a little high to you for a neural gene, it seems a little high to me. You ought to check it out some time, they have no clue what the molecular mechanism was that produced the positive evolution that would have had to produce the most dramatic adaptation in evolution.

Two points: 1) You've mangled the quotation(s) from the paper, and 2) no, that does not seem like a high mutation rate to me. It's typical of estimates of the overall point mutation rate in the genome, and there is nothing unusual about the mutation rate for neural genes that I know of. (They evolve more slowly than some genes, and a lot more slowly than nonfunctional sequence, but that isn't because they mutate more slowly.)

Oh, and mutations aren't transcript errors (except, as has been pointed out twice, for rare exceptions). They're either replication errors or in situ chemical changes.

 

[mark kennedy]

Two points: 1) You've mangled the quotation(s) from the paper,

It's not a quote exactly, it's more like a paraphrase with a citation. Just trying to isolate some key evidences while you guys mangle the most basic definitions in biology.

"Mutations can be caused by copying errors in the genetic material during cell division" (Wikipedia). When is the DNA copied? During the S Phase of the cell cycle during transcription. You have done this before when you got on that pedantic bandwagon about bp does not mean base pair. You only wanted to make a mutation of a million base pairs the same as a single point mutation and it reeks.

You guys are not defending science, your distorting it. "In the living cell, DNA undergoes frequent chemical change, especially when it is being replicated (in S phase of the eukaryotic cell cycle). Most of these changes are quickly repaired. Those that are not result in a mutation. Thus, mutation is a failure of DNA repair." (Kimble Biology pages).

Some facts you claim I mangled because you don't want to address the real world problem of explaining them.

1. ASPM has 28 coding exons, spanning 62 kb
2. Coding a huge protein of 3477 amino acids
3. assumed that all 1019 indels with sizes that are multiples of three nucleotides
4. That they do not disrupt an ORF
5. Accumulated at a point mutation rate of 1 x 10-9/site/year​

I always know when I have you guys, you resort to semantical hair splitting and as many ad hominem attacks as you can get in one right after the other.

Notice the challenge to identify the molecular mechanism responsible was ignored. It always is especially by scientists who know there is none. The only way of explaining it is stretching it over 5 to 25 million years because that is the only way accumulated neutral and slightly deleterious mutations could accumulate. Never mind the fact that our mythical ancestors have a cranial capacity of between 400cc and 500cc 2 million years ago, we need more time to make this myth statistically feasible.

If you want to believe that there is some unknown molecular mechanism for adapting the size and complexity of the human brain from that of apes I really don't care. Just don't pretend it's random mutations because I know for a fact that you know better.

and 2) no, that does not seem like a high mutation rate to me. It's typical of estimates of the overall point mutation rate in the genome, and there is nothing unusual about the mutation rate for neural genes that I know of. (They evolve more slowly than some genes, and a lot more slowly than nonfunctional sequence, but that isn't because they mutate more slowly.)

Do they always come in multiple of three Steve?

Oh, and mutations aren't transcript errors (except, as has been pointed out twice, for rare exceptions). They're either replication errors or in situ chemical changes.

There is a reason I listen to this endless banter, it because I am genuinely interested in molecular mechanisms capable of producing accelerated adaptation. It's as simple as that, if you think I am going to blindly succumb to these semantical shell games you don't have a clue what I'm after.

"...transcription may be implicated as a major cause of background transition mutations in nature..." A Biochemical Mechanism for Nonrandom Mutations and Evolution
​

All I said originally was:

I don't know how much a transcript error, deletion, insertion, point mutation or rearrangement can help adapt organisms over time. It's difficult for me to track down but I get the impression that I have stumbled into a very complicated world of exploration.

This was the response:

Firstly, "transcript errors" have nothing to do with mutations. It's high time you get your terminology and conceptual understanding correct. Secondly, are you simply trying to say there are no such things as beneficial mutations?

I never said anything about there being no beneficial effects from mutations. What I have realized is that many of the things that are passing as mutations are not mutations at all, they are molecular mechanisms:

The mechanism of gene duplication as the means to acquire new genes with previously nonexistent functions is inherently self limiting in that the function possessed by a new protein, in reality, is but a mere variation of the preexisted theme. As the source of a truly unique protein, I suggest an unused open reading frame of the existing coding sequence. Only those coding sequences that started from oligomeric repeats are likely to retain alternative long open reading frames. Analysis of the published base sequence residing in the pOAD2 plasmid of Flavobacterium Sp. K172 indicated that the 392-amino acid-residue-long bacterial enzyme 6-aminohexanoic acid linear oligomer hydrolase involved in degradation of nylon oligomers is specified by an alternative open reading frame of the preexisted coding sequence that originally specified a 472-residue-long arginine-rich protein.

(Birth of a unique enzyme from an alternative reading frame of the preexisted, internally repetitious coding sequence. PNAS 1984)​

But "an extraordinary leap in adaptive evolution" is the explanation for how the human brain evolved from that of apes, unless you have any good evidence to show that adaptive evolution cannot occur.

There it is in a nutshell, I have to prove that adaptive evolution cannot occur and deal with two pages of semantical hairsplitting over the term transcript error I used as an example of a mutation.

Like everything else I am going to have to do this the hard way. The main reason being that main stream science is hopelessly biased against all forms of theistic reasoning. That is all this comes down to because if it were otherwise we would be talking about known molecular mechanisms that produce adaptive traits. Instead you jerk my words out of context and twist my words to mean something I never intended and certainly never said. Then carefully prepared expositions of scientific literature pointing out serious difficulties with inferred mutation rates from direct comparisons of highly conserved genes are trampled.

This has nothing to do with science, if it were then you wouldn't be derailing the thread with this disingenuous semantical double talk.

Transcript errors have nothing to do with mutations?

You ignore this grossly erroneous statement and then attack me in concert because I said I don't know how much a transcript error, point mutation...etc had to do with an adaptation. You have not only distorted what I was saying but derailed what might have been an interesting conversation.

I am appalled.

 

[Deamiter]

Wait, mark -- the reason we got into transcription errors is that you stated directly that they account for a majority of mutations. In fact, you used this as evidence for your claim that shernen doesn't know what he is talking about!

I'm not totally wrong? He can't recognize that a mutation most often is a transcript error and flagrantly denies that it is...

When you claim something outrageous and claim it discredits those who disagree with you, and get called on it, you can't just say, "it's splitting symantics." Your attack on shernen's understanding of central dogma was based solely on this statement that mutations most often are transcription errors. You really want us all to ignore that this attack was based on a blatant falsehood (that mutations are most often created by transcription errors) and go back a few days to where you were claiming that it's impossible for mutations to accumulate in ASPM?

The calculation you need to do should be simple and I've never seen you do it. What is the maximum allowed mutation rate in ASPM? You cite the rate needed to account for ASPM mutations, but you've never compared it to a similar number so you're just saying "this number is big so I don't believe it could have happened."

 

[shernren]

Have I mangled the discussion? Remember, if you hadn't made the error of saying mutations are transcription errors, then we wouldn't have had to chase you down this rabbit hole in the first place. We're trying to help you correct your basic errors in genetic concepts so that you won't sound like a fool when you're out there trying to engage others more knowledgeable than we are. It would have been easy enough to post a "Transcript errors are not mutations, mark, you're being an idiot and you don't deserve any of our time" comment and write you off as just another misinformed critic (when there are, actually, reasonably well-informed critics). We're trying to stop you from self-destructing your own arguments!

The reason I'm doing this is because definitions are extremely important, especially in contentious issues like this, and if you not only have different definitions, but have no good reason for supporting them, then you get into a whole lot of trouble. Remember that little spat when some of the TEs here argued that since they can call themselves "evolutionary creationists" they could sneak into the Creationist forum? Definitions are important. Without any common ground there is no way we can make sense to you.

It's not a quote exactly, it's more like a paraphrase with a citation. Just trying to isolate some key evidences while you guys mangle the most basic definitions in biology.

"Mutations can be caused by copying errors in the genetic material during cell division" (Wikipedia). When is the DNA copied? During the S Phase of the cell cycle during transcription. You have done this before when you got on that pedantic bandwagon about bp does not mean base pair. You only wanted to make a mutation of a million base pairs the same as a single point mutation and it reeks.

You guys are not defending science, your distorting it. "In the living cell, DNA undergoes frequent chemical change, especially when it is being replicated (in S phase of the eukaryotic cell cycle). Most of these changes are quickly repaired. Those that are not result in a mutation. Thus, mutation is a failure of DNA repair." (Kimble Biology pages).

Now, DNA replication takes place during the S phase. DNA transcription doesn't. Are we clear?

 

[mark kennedy]

Wait, mark -- the reason we got into transcription errors is that you stated directly that they account for a majority of mutations. In fact, you used this as evidence for your claim that shernen doesn't know what he is talking about!

No, what I did was mention transcript errors and other mutations saying I was not sure how much they had to do with adaptations. He doesn't know what he is talking about if he thinks that transcript errors have nothing to do with mutations. No one bothers to correct this guy despite the fact he repeats the same error again and again. Like I said, it's fairly typical.

When you claim something outrageous and claim it discredits those who disagree with you, and get called on it, you can't just say, "it's splitting symantics." Your attack on shernen's understanding of central dogma was based solely on this statement that mutations most often are transcription errors. You really want us all to ignore that this attack was based on a blatant falsehood (that mutations are most often created by transcription errors) and go back a few days to where you were claiming that it's impossible for mutations to accumulate in ASPM?

I never said it was impossible for over a thousand indels to accumulate in a huge protein coding gene over 62 kb long. I said the molecular mechanism was unknown and that researchers unanimously admitted it in the peer reviewed literature. It was quoted, cited and linked along with detailed expositions. The reaction was this pedantic chant that transcript errors are not mutations which is wrong.

The calculation you need to do should be simple and I've never seen you do it. What is the maximum allowed mutation rate in ASPM? You cite the rate needed to account for ASPM mutations, but you've never compared it to a similar number so you're just saying "this number is big so I don't believe it could have happened."

None of the facts have gained the slightest interest of the posters in this thread and never will. I don't need to meet some impossible burden of proof I know you guys are just going to argue in circles until I get tired of it because you always do.

 

[mark kennedy]

Have I mangled the discussion? Remember, if you hadn't made the error of saying mutations are transcription errors, then we wouldn't have had to chase you down this rabbit hole in the first place.

Your not going to get off the hook that easy, your the one that said that transcript errors have nothing to do with mutations. What I said was that I don't know how much transcript errors, point mutations...etc have to do with adaptations. You were not even addressing what I said, what you did was twist my words. Then you tried to give me an impossible burden of proof saying that I had to prove that adaptations were impossible.

We are not chasing rabbits, you are chasing the wind.

We're trying to help you correct your basic errors in genetic concepts so that you won't sound like a fool when you're out there trying to engage others more knowledgeable than we are.

The arguments don't change, that's the whole thing. I do know the basics and they don't have a molecular mechanism for the evolution of the human brain from that of an ape. True, the will argue endlessly that basic errors are being made but it's all a performance. They know they have no demonstrated or directly observed molecular mechanism that can produce an adaptive trait in the human brain.

That's why they would rather agree with your erroneous statement then face the facts.

It would have been easy enough to post a "Transcript errors are not mutations, mark, you're being an idiot and you don't deserve any of our time" comment and write you off as just another misinformed critic (when there are, actually, reasonably well-informed critics). We're trying to stop you from self-destructing your own arguments!

It would have been just as easy to admit that any DNA-destabilizing event will increase mutation rates. Things like polymerase and proofreading errors during DNA replication, as well as recombination, transcription, and repair. It would have been easy enough to correct your obvious error and moved on to molecular mechanisms that are known to create adaptive traits and improved fittness but they didn't.

They don't because they do not dare accept theistic reasoning in any scientific context.

The reason I'm doing this is because definitions are extremely important, especially in contentious issues like this, and if you not only have different definitions, but have no good reason for supporting them, then you get into a whole lot of trouble. Remember that little spat when some of the TEs here argued that since they can call themselves "evolutionary creationists" they could sneak into the Creationist forum? Definitions are important. Without any common ground there is no way we can make sense to you.

Oh! Now I see, you are calling me a fool and an idiot because you want to help me have good definitions. Let's get something straight, the scientific definition of evolution is that change of allele frequencies in populations over time. That makes everyone, including creationists an evolutionist. The laws of science involved in the inheritance of traits are never an issue for creationists. It is the suppositions of common ancestry that rejects all theistic inference in the causative chain that creationists reject.

You want to make sense to me then stop distorting basic biology because what you are saying makes no sense at all.

Now, DNA replication takes place during the S phase. DNA transcription doesn't. Are we clear?

77% of these mutations originate on the nontranscribed strand in E. coli mutants unable to repair deaminated cytosines. This suggests that the unprotected single strand in the transcription "bubble" is significantly more vulnerable to mutations than the transcribed strand, which is protected as a DNA-RNA hybrid​

What I said was that I don't know how much transcription errors, point mutations...etc have to do with adaptations.

Firstly, "transcript errors" have nothing to do with mutations. It's high time you get your terminology and conceptual understanding correct. Secondly, are you simply trying to say there are no such things as beneficial mutations?

Any DNA-destabilizing event will increase mutation rates. (A Biochemical Mechanism for Nonrandom Mutations and Evolution
Barbara E. Wright Journal of Bacteriology, June 2000)

Are we clear?

 

[mark kennedy]

I was lagged so I managed to double post, must have hit the enter key too many times. That's ok, it will give me a chance to introduce Genesis to the Genesis and Genetics thread.

According to Christian tradition, original sin is the general condition of sinfulness (lack of holiness) into which human beings are born (Psalm 51:5). Original sin is also called hereditary sin, birth sin, or person sin. Used with the definite article ("the original sin"), it refers to the first sin, committed when Adam and Eve succumbed to the serpent's temptation.​

Original Sin from Wikipedia, the free encyclopedia

Original sin may be taken to mean: (1) the sin that Adam committed; (2) a consequence of this first sin, the hereditary stain with which we are born on account of our origin or descent from Adam.

From the earliest times the latter sense of the word was more common, as may be seen by St. Augustine's statement: "the deliberate sin of the first man is the cause of original sin" (De nupt. et concup., II, xxvi, 43). It is the hereditary stain that is dealt with here. As to the sin of Adam we have not to examine the circumstances in which it was committed nor make the exegesis of the third chapter of Genesis.
​

Original Sin, from New Advent the Catholic Encyclopedia

 

[sfs]

It's not a quote exactly, it's more like a paraphrase with a citation.

Don't put paraphrases into block quotation format, since it misleads the reader. And you should avoid paraphrasing, since you conisistently misunderstand scientific papers, including this one.

"Mutations can be caused by copying errors in the genetic material during cell division" (Wikipedia). When is the DNA copied? During the S Phase of the cell cycle

Correct.

during transcription.

That's the incorrect part. DNA is not replicated (copied into DNA) during transcirption. During transcription it is copied into RNA. Replication is a different process.

You have done this before when you got on that pedantic bandwagon about bp does not mean base pair. You only wanted to make a mutation of a million base pairs the same as a single point mutation and it reeks.

No, Mark, I wanted to explain some basic biology to you. Your response was rudeness and an accusation that I was lying. You obviously still don't understand what I (and many other people) told you. (Note: I never said that "bp" does not mean base pair -- that's a little fantasy you cooked up yourself.)

You guys are not defending science, your distorting it. "In the living cell, DNA undergoes frequent chemical change, especially when it is being replicated (in S phase of the eukaryotic cell cycle). Most of these changes are quickly repaired. Those that are not result in a mutation. Thus, mutation is a failure of DNA repair." (Kimble Biology pages).

Right. And what does this have to do with transcription, which takes place throughout the cell cycle, and which does not result in replication of DNA?

Some facts you claim I mangled because you don't want to address the real world problem of explaining them.

1. ASPM has 28 coding exons, spanning 62 kb
2. Coding a huge protein of 3477 amino acids
3. assumed that all 1019 indels with sizes that are multiples of three nucleotides
4. That they do not disrupt an ORF
5. Accumulated at a point mutation rate of 1 x 10-9/site/year
​

The first two are facts. The last three are all errors you've made from misreading the Zhang paper. The paper describes a model. In that model, indels come in all sizes. They assume that those indels that happen to be multiples of three bases will not disrupt the ORF; the others will. They also assume that point mutations (which are not indels) occur at a rate of 1x10-9/site/year. Some of those point mutations, the ones that produce a premature stop codon, will also disrupt the ORF.

That's what the paper actually says. The point of the model is to demonstrate that ASPM has not experienced a loss of selective constraint, and is in fact under strong purifying selection. Since this is a point you accept, I have no clue why you have gone off on this tangent.

I always know when I have you guys, you resort to semantical hair splitting and as many ad hominem attacks as you can get in one right after the other.

Mark, you're making a fool out of yourself. (If you want to interpret that statement as evidence that you have superior insight into biology to all the actual biologists, and that I'm only resorting to ad hominem comments because of your insight, you can do so. If you do, you'll simply be making a bigger fool out of yourself. Your call.)

If you want to believe that there is some unknown molecular mechanism for adapting the size and complexity of the human brain from that of apes I really don't care. Just don't pretend it's random mutations because I know for a fact that you know better.

You know many things that just aren't so.

Do they always come in multiple of three Steve?

No. "In the above genomic data analyzed, 19% of the total 1019 indels are of sizes that are multiples of three nucleotides." That's from the same paragraph in the Zhang paper that you already quoted.

"...transcription may be implicated as a major cause of background transition mutations in nature..." A Biochemical Mechanism for Nonrandom Mutations and Evolution
​

Quite. It is certainly possible that transcription causes mutations to occur, just as recombination probably causes mutations to occur. In both cases the DNA is exposed and subject to damage during the process. The mutations are not transcription errors, however; transcription errors are mistakes in the transcript (the RNA copy), while the mutations are changes to the original DNA. And note that this is a different mutation process than the one you were talking about earlier, which occurs during DNA replication in S phase.

All I said originally was:
[statement about "transcript error"]

Yes, and what you originally said was wrong. Transcript errors (that is, errors in transcripts) are not a source of mutation here.

 

[sfs]

I never said it was impossible for over a thousand indels to accumulate in a huge protein coding gene over 62 kb long. I said the molecular mechanism was unknown and that researchers unanimously admitted it in the peer reviewed literature. It was quoted, cited and linked along with detailed expositions.

What the heck are you talking about here? No one has suggested that ASPM was accumlated from over a thousand indels. The thousand indels in the Zhang paper had nothing to do with the origin of ASPM. All the 1019 indels were was an empirical sample of indels that could provide an estimate of the size distribution of real indels.

 

[Mallon]

It's always fun watching a machinist trying to debate a trained geneticist on the issue of... genetics.

 

[shernren]

Your not going to get off the hook that easy, your the one that said that transcript errors have nothing to do with mutations. What I said was that I don't know how much transcript errors, point mutations...etc have to do with adaptations.

But why even bring up transcript errors at all? They have nothing to do with heritable genetics.

77% of these mutations originate on the nontranscribed strand in E. coli mutants unable to repair deaminated cytosines. This suggests that the unprotected single strand in the transcription "bubble" is significantly more vulnerable to mutations than the transcribed strand, which is protected as a DNA-RNA hybrid​

....

Any DNA-destabilizing event will increase mutation rates. (A Biochemical Mechanism for Nonrandom Mutations and Evolution
Barbara E. Wright Journal of Bacteriology, June 2000)

Are we clear?

Look carefully at that diagram: it is the untranscribed strand that is more vulnerable to mutations. A transcript error has not caused the mutation here since there is no error within the RNA transcript.

In any case yes, let me grab some popcorn and watch mark try to teach sfs some genetics ...

 

[sfs]

An article about ASPM that I mentioned earlier has now appeared in print (Science, 316:370, "Comment on 'Ongoing Adaptive Evolution of ASPM, a Brain Size Determinant in Homo sapiens', Fuli Yu et al). It attacks the claim that ASPM shows evidence for very recent positive selection. The abstract:

"Mekel-Bobrov et al. (Reports, 9 September 2005, p. 1720) suggested that ASPM, a gene associated with microcephaly, underwent natural selection within the last 500 to 14,100 years. Their analyses based on comparison with computer simulations indicated that ASPM had an unusual pattern of variation. However, when we compare ASPM empirically to a large number of other loci, its variation is not unusual and does not support selection."