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Author Topic:   Genetics and Human Brain Evolution
eggasai
Inactive Member


Message 61 of 157 (359745)
10-29-2006 11:41 PM
Reply to: Message 15 by mick
10-26-2006 6:58 AM


Re: Getting the numbers right
quote:
Eggasai, you are completely wrong here. The Nature article cites a total nucleotide divergence of around 4%; 1% caused by 35 million substitution mutations, and 3% caused by a total of 5 million indel mutations.
You are obviously confusing overall divergance with comparisons of genes. The 95% is overall, the protein coding genes show differnces at an amino acid sequence level in 83% of the protein codeing genes. In the Chimapnzee Chromosome 22 paper the found gross stuctural changes would have been required in 20% of the genes.
quote:
You appear to have cherry-picked the lowest measure of identity you could find in the article (29%) in order to bolster your case. However that is the percentage of whole proteins (not nucleotide positions) which are identical in terms of their complete amino acid sequence.
I keep going over the same ground because you don't ask questions you just contradict me. The amino acid sequence diverge which is clearly an indication that the amino acid sequences would have had to change, that's the point. Eventually I will get into applying this to the known mutation rate but it's going to take a lot longer then usual since you are unfamilar with comparitive genomics.
quote:
to repeat what the Nature article actually says: Around 96% of the total genome is identical (not 29% as you imply). These differences were caused by a total of 40 million mutation events (not 145 million, as you claim)
Again, that's 29% of the protien coding genes are identical. With 35 million nucleotide substitutions, 5 million indels totalling 90 Mb and 20 Mb worth of chromosomal rearrangements in 9 pericentric inversions. That comes to 145 Mb that have to diverge in 7 million years with hundreds if not thousands of mutations in hundreds if not thousands of genes. In 7 million years it would require 20 mutations fixed in the respective genomes per year for 7 million years.
Again, you have confused the amount of divergance with the percentage of protein coding genes that are identical. If you would stop trying to make me feel like I don't know what I'm talking about I'll break down the particulars to you. Untill then we will just have to keep this volleyball thing up.
quote:
Anyway, if the fact that 29% of whole proteins are identical in human and chimp seems low to you, you should spend a moment considering the implications. According to the Nature article, the remaining 71% of proteins differed by an average of only two amino acids. The average length of a protein is around 1000 amino acids. This means that the probability that an amino acid from a chimp protein is identical to the corresponding amino acid in the human orthologue is equal to : (0.29 * 1.0) + (0.71 * 998/1000) = 99.858%.
The probability argument is worse then useless, they never attempted anything like that. The simply said that they attributed the divergance in the genes to regional variation.
quote:
So the average probability of identity for single amino acids is close to 100% and over 99.5%, whichever way you look at it. NOT 29%!!!
I don't know what the point of that was and I'm not sure you do either.
quote:
Finally, there is your assertion that the natural mutation rate cannot account for the number of differences between chimp and human genomes. Let's say that the generation length for humans, chimps and their proto-species is around 15-20 years. Over the six million years since divergence, that gives us 300,000 to 400,000 generations per lineage. Since there are two lineages that can accumulate mutations, we have a total of 600,000 to 800,000 fertilization events separating a modern chimp from a modern human. Given that the nature paper declared 40 million mutation events, that gives us 50-66 mutations fixed per POPULATION per generation.
I don't know what you used to calculate the number of fertilization events but there are 350,000 generations (est. 20 years) in 7 million years of continutous evolution. We have no idea if the indels, some as long as a million bps long, were all one time events. They indentified 5 million differences totalling 90 Mb. They averaged 300 bp and they were found mostly in alu elements but also in protein codeing, regulatory and outlier genes. You really should read the Chimpanzee Genome Consortium's paper.
quote:
The number of new mutations arising per individual is around 100. If we were to assume a mean historical effective population size of around 25,000 for each proto-species (consistent with chimpanzee demographic data), the observed divergence between chimps and humans requires something of the order of 2-3 mutations to be fixed for each 100,000 mutations occuring. That doesn't seem unreasonable by any means.
With a mutation rate of 2 x 10^-8 it's 2 mutations per 100,000,000 with approximatly 3 billion nucleotides in the respective genomes (actually 2.74 billion). That comes to 60 mutations per diploid generation so you double it, which comes to 120 per generation.
You probably have anywhere from 120-170 germline mutations in you own copy of the genome. Most of them, and I do mean virtually all, do nothing at all because they are either in the junk DNA or they don't change functionally important genes. If you had one in one of the regulatory genes involved in the development of your neocortex you would never have been born.
This might take longer then usuall but we will get there, trust me.

This message is a reply to:
 Message 15 by mick, posted 10-26-2006 6:58 AM mick has replied

Replies to this message:
 Message 63 by Wounded King, posted 10-30-2006 3:14 AM eggasai has not replied
 Message 64 by mick, posted 10-30-2006 4:23 AM eggasai has replied

  
Wounded King
Member
Posts: 4149
From: Cincinnati, Ohio, USA
Joined: 04-09-2003


Message 62 of 157 (359754)
10-30-2006 3:11 AM
Reply to: Message 55 by eggasai
10-29-2006 6:54 PM


Re: "natura non facit saltum"
I neve questioned the existence of in frame insertions, what I questioned was whether you had anything to support your contention that...
most of the neural genes would require in-frame indels of considerable length
Rather than support you that the paper mentions only 2 neural genes sepcifically with large indels and in both cases the large indels involved are in intronic regions which will not be translated into protein and consequently there is absolutely no requirement for them to be in frame.
None of the gene products they identify in their supplementary data as having internal amino acid insertions or deletions stand out as being neural, in fact several are clearly structural such as keratin and collagen.
That isn't near as astonishing as the inframe indels that would be required in the regulatory genes or the outliers, particularly the ones that are functionally biased in crucial neural development.
Again you make the same nonsense statement and again it seems predicated on your failure to understand basic biology which you have yet to adequately address. Why is an indel required? Why is a single nucleotide substitution in a codon leading to a change in the resulting amino acid not sufficient? Or indeed why are all manner of changes in 'non-coding' regions not sufficient given their potential for substantial changes in the expression of genes. Why do you think the paper you just linked to goes into details of their analysis of untranslated regions and upstream regions for transcription factor binding sites? Because they think that changes in gene expression they detected are linked to changes in those regions, regions where questions of frame are wholly irrelevant.
It seems as obvious as it needs to if you are aquainted with the scientific literature on the subject. Why don't you google mutations and human neural genes or just read some of the papers I often quote, cite and link.
I'm not sure how you have managed to fail to notice that I have done just that with several of the papers you have brought up, and in many cases you have just left my analyses lying fallow. None of those papers have supported your major contentions which I have had issue with.
Believe me I am well familiar with data on the molecular genetics of evolution, particularly within the developmental area. And my reading of the literature doesn't suggest to me in any way that your points have any support.
The only times that relaxed functional constraint is obsered is rare instances where it improves the enzymes ability purge transcript errors. The only reason that the mutation rate is not 0 is because of the physiological costs of adaptation. Relaxed funtional constraint, 'by it's nature' runs the risk of severly deleterious effects due to an increase in the number of them. I fail to accept the logic you are using because...how can I say this nicely... it oversimplifies things way too much.
I'm not sure what you understand by 'relaxed functional constraint'. The reason the 'functional constraint' is 'relaxed' is exactly because more mutations are no longer deleterious due to some change in a nother part of the system, either environmental or in the genetics of the organism. So deleterious mutations are no more likely to occur than ever because deleterious muttions will still be weeded out, it is simply that of all the possible mutations less of them are deleterious due to the relaxation of the functional constraints. In terms of the context of the original gene in its original environment many of these mutations would be deleterious but the deleterious nature of them as it pertains to function is highly context dependent.
And then you go on to argue from ARN, this seems to be a real slippage in standard from references to the work of the HGP. Your quote doesn't even seem to be in the article that you linked, making it source completely anonymous, and neither makes a cogent argument for your position, if you think there is such an argument to be made then why not make it in your own words. If you are just culling half understood arguments from creationist sites then why not stop now until you at least fully understand what you are arguing.
TTFN,
WK

This message is a reply to:
 Message 55 by eggasai, posted 10-29-2006 6:54 PM eggasai has replied

Replies to this message:
 Message 68 by eggasai, posted 10-30-2006 8:43 PM Wounded King has replied

  
Wounded King
Member
Posts: 4149
From: Cincinnati, Ohio, USA
Joined: 04-09-2003


Message 63 of 157 (359755)
10-30-2006 3:14 AM
Reply to: Message 61 by eggasai
10-29-2006 11:41 PM


Re: Getting the numbers right
If you had one in one of the regulatory genes involved in the development of your neocortex you would never have been born.
This is the kind of claim that requires evidence, and it is the same claim which required evidence which I have been asking you to back up since the first page of this thread.
Could you now provide some evidence to support this claim?
TTFN,
WK

This message is a reply to:
 Message 61 by eggasai, posted 10-29-2006 11:41 PM eggasai has not replied

  
mick
Member (Idle past 4985 days)
Posts: 913
Joined: 02-17-2005


Message 64 of 157 (359757)
10-30-2006 4:23 AM
Reply to: Message 61 by eggasai
10-29-2006 11:41 PM


Re: Getting the numbers right
Let's try this one more time.
eggasai writes:
I keep going over the same ground because you don't ask questions you just contradict me.
Okay, this time I will ask you questions and I'll try to keep everything clear. In return, perhaps you could answer the questions directly and keep personal insults to a minimum.
eggasai writes:
With 35 million nucleotide substitutions, 5 million indels totalling 90 Mb and 20 Mb worth of chromosomal rearrangements in 9 pericentric inversions. That comes to 145 Mb that have to diverge in 7 million years with hundreds if not thousands of mutations in hundreds if not thousands of genes.
Question: what do you mean when you say "hundreds if not thousands of mutations in hundreds if not thousands of genes"? My understanding is that the number of mutations being tallied here was measured across the whole genome, not just in the genes. Even if the mutations were measured only in coding sequences (which I do not recall is the case) that would still be tens of thousands of genes, not hundreds. Are we not talking about 40 million and nine mutations in the entire genome?
Question: under the assumption that mutations are distributed randomly, how many mutations per gene do you think these figures represent? Here are my calculations: About 1.5% of the human genome consists of protein-coding sequences (Reference). if the 40 million and nine mutations are distributed randomly, that gives us an expected number of 600,000 mutations in the coding portion of the genome. Since there are around 35,000 protein-coding genes in the human body (Reference), that gives us an expected number of 17 mutations per gene. Would you agree with this logic, and if not, why not? I know that the assumption of random distribution of mutations is not realistic, but I'd like to know if you agree with the ballpark figure of tens of mutations per gene rather than hundreds or thousands of mutations per gene.
eggasai writes:
In 7 million years it would require 20 mutations fixed in the respective genomes per year for 7 million years.
Question: why 20 mutations per year? You have said that there were forty million and nine mutations. Forty million and nine divided by seven million is 5.7, not 20.
Question: what do you mean by "in their respective genomes"? The total number of mutations we are talking about here is the SUM of the mutations that have occurred either in the chimp lineage or in the human lineage. Just by comparing the chimp to the human, we cannot tell which lineage the mutations arose in. This is a minor point but I would like to know if you agree.
After we've sorted out these basic facts, I have some more questions to ask, if that's okay with you.
Thanks! I think short focussed posts like these will help the debate to move along nicely. I am happy to retract anything here if I've made a mistake so let's try to have a productive discussion.
Mick
Edited by mick, : added pargraph starting with: Question: what do you mean when you say "hundreds if not thousands of genes"
Edited by mick, : No reason given.

This message is a reply to:
 Message 61 by eggasai, posted 10-29-2006 11:41 PM eggasai has replied

Replies to this message:
 Message 65 by Wounded King, posted 10-30-2006 5:08 AM mick has replied
 Message 71 by eggasai, posted 10-30-2006 9:47 PM mick has not replied

  
Wounded King
Member
Posts: 4149
From: Cincinnati, Ohio, USA
Joined: 04-09-2003


Message 65 of 157 (359760)
10-30-2006 5:08 AM
Reply to: Message 64 by mick
10-30-2006 4:23 AM


Eggasai is producing mashups of his previous posts.
I know I'm not Eggasai but the origins of some of these mistakes is obvious.
what do you mean when you say "hundreds if not thousands of mutations in hundreds if not thousands of genes"?
Eggasai is mixing and matching bits from his previous posts. The 'hundreds if not thousands' schtick comes from the discussion of the differences in genes relevant to neural development in chimps and humans, in fact it is lifted almost straight from the press release for the Lahn(2004) paper.
Mick writes:
why 20 mutations per year? You have said that there were forty million and nine mutations. Forty million and nine divided by seven million is 5.7, not 20.
Because Eggasai's calculation is actually based on the number of Mbs of difference in the genome rather than the actual number of mutations. 145Mb/7 million =20.7. He even said in Message 5 ...
Eggasai writes:
For these differences to have to accumulate would require 20 nucleotide fixed in the respective genomes, on average,for 7 million years.
What he has done is treat single nucleotide differences and mutations as if they were synonymous.
TTFN,
WK

This message is a reply to:
 Message 64 by mick, posted 10-30-2006 4:23 AM mick has replied

Replies to this message:
 Message 66 by mick, posted 10-30-2006 5:34 AM Wounded King has replied
 Message 70 by eggasai, posted 10-30-2006 9:03 PM Wounded King has not replied

  
mick
Member (Idle past 4985 days)
Posts: 913
Joined: 02-17-2005


Message 66 of 157 (359762)
10-30-2006 5:34 AM
Reply to: Message 65 by Wounded King
10-30-2006 5:08 AM


Re: Eggasai is producing mashups of his previous posts.
wounded king writes:
Eggasai is mixing and matching bits from his previous posts. The 'hundreds if not thousands' schtick comes from the discussion of the differences in genes relevant to neural development in chimps and humans, in fact it is lifted almost straight from the press release for the Lahn(2004) paper
thanks, that's good to know. Lahn's paper was actually based on a comparison of human and macaque, which represents 20-25 million years of evolution. But eggasai is cramming this number of mutations accumulating in 20-25 million years into the 7 million years separating chimp from human.
From the press release:
quote:
evolution of the human brain probably involves hundreds if not thousands of mutations in perhaps hundreds or thousands of genes -- and even that is a conservative estimate...It is nothing short of spectacular that so many mutations in so many genes were acquired during the mere 20-25 million years of time in the evolutionary lineage leading to humans
Well, that's one problem solved isn't it?
Mick
Edited by mick, : added quote from news release

This message is a reply to:
 Message 65 by Wounded King, posted 10-30-2006 5:08 AM Wounded King has replied

Replies to this message:
 Message 67 by Wounded King, posted 10-30-2006 5:46 AM mick has not replied
 Message 69 by eggasai, posted 10-30-2006 8:57 PM mick has not replied

  
Wounded King
Member
Posts: 4149
From: Cincinnati, Ohio, USA
Joined: 04-09-2003


Message 67 of 157 (359765)
10-30-2006 5:46 AM
Reply to: Message 66 by mick
10-30-2006 5:34 AM


Re: Eggasai is producing mashups of his previous posts.
Lahn's paper was actually based on a comparison of human and macaque
wow, I completely missed that!
So his second point in his OP ...
The genes involved and the number of changes that would be required for humans to evolve from apes.
Is actually based on a paper about the differences between humans and monkeys, doh!!
This guy seriously needs to do his homework, maybe I do too since I missed it.
TTFN,
WK

This message is a reply to:
 Message 66 by mick, posted 10-30-2006 5:34 AM mick has not replied

  
eggasai
Inactive Member


Message 68 of 157 (359988)
10-30-2006 8:43 PM
Reply to: Message 62 by Wounded King
10-30-2006 3:11 AM


Re: "natura non facit saltum"
quote:
Rather than support you that the paper mentions only 2 neural genes sepcifically with large indels and in both cases the large indels involved are in intronic regions which will not be translated into protein and consequently there is absolutely no requirement for them to be in frame.
None of the gene products they identify in their supplementary data as having internal amino acid insertions or deletions stand out as being neural, in fact several are clearly structural such as keratin and collagen.
You seem to be confusing the inframe indels with the gross structural changes that would be required in the protein coding genes discussed in the Chromosome 22 paper. I don't know why you are so indent of conflating the evidence but I suppose it's just a diversionary tactic. It would really help you if you learned to focus on one thing at a time.
quote:
Again you make the same nonsense statement and again it seems predicated on your failure to understand basic biology which you have yet to adequately address. Why is an indel required? Why is a single nucleotide substitution in a codon leading to a change in the resulting amino acid not sufficient? Or indeed why are all manner of changes in 'non-coding' regions not sufficient given their potential for substantial changes in the expression of genes. Why do you think the paper you just linked to goes into details of their analysis of untranslated regions and upstream regions for transcription factor binding sites? Because they think that changes in gene expression they detected are linked to changes in those regions, regions where questions of frame are wholly irrelevant.
I was talking here about the HAR1 regulatory gene, it's 118 nucleotides long and 18 of them diverge between chimps and humans. You are going off on somekind of a tangent here and making vauge references to a paper, maybe you should quote it at least.
quote:
I'm not sure how you have managed to fail to notice that I have done just that with several of the papers you have brought up, and in many cases you have just left my analyses lying fallow. None of those papers have supported your major contentions which I have had issue with.
Believe me I am well familiar with data on the molecular genetics of evolution, particularly within the developmental area. And my reading of the literature doesn't suggest to me in any way that your points have any support.
The papers themselves are being ignored since you seem intent on talking in generalities. You blew by my point about the mutation rate reguired for 145 Mb worth of divergance. That still comes to a mean average of 20 per year for 7 million years. Then it stops in modern times and levels off at 2x10-8 which it 2 per 100,000,000 nucleotides per diploid generation. The problem is that you don't want to actually look at the evidence. I assume by your response that you either don't intend to look up the affects of mutations on functionally biased neural genes or you don't want to talk about them.
quote:
I'm not sure what you understand by 'relaxed functional constraint'. The reason the 'functional constraint' is 'relaxed' is exactly because more mutations are no longer deleterious due to some change in a nother part of the system, either environmental or in the genetics of the organism. So deleterious mutations are no more likely to occur than ever because deleterious muttions will still be weeded out, it is simply that of all the possible mutations less of them are deleterious due to the relaxation of the functional constraints. In terms of the context of the original gene in its original environment many of these mutations would be deleterious but the deleterious nature of them as it pertains to function is highly context dependent.
And then you go on to argue from ARN, this seems to be a real slippage in standard from references to the work of the HGP. Your quote doesn't even seem to be in the article that you linked, making it source completely anonymous, and neither makes a cogent argument for your position, if you think there is such an argument to be made then why not make it in your own words. If you are just culling half understood arguments from creationist sites then why not stop now until you at least fully understand what you are arguing.
You asked about the cleavage stage so I went ahead and linked you to a paper that showed a typical Darwinian picture of it. You keep missing my points because you don't like going into the specifics. You want to know what my argument here is in comprehensive terms? Here you go.
145 Mb diverge in 7 million years is far beyond the range of the observed mutation rate. It comes to 20 million nucleotides per year for 7 million years. With human populations at about 6 billion our geneomes diverge by 1/10 of 1% and are rarely fixed.
The physiological costs of the human brain growing from that of an ape is enormous and refutes Darwinian anagenesis scenerios completly:
"For example, in comparison with chimpanzees, the brain weight of humans is 250% greater while the body is only 20% heavier (MCHENRY 1994 ). The dramatic evolutionary expansion of the human brain started from an average brain weight of 400-450 g 2-2.5mya million years (MY) ago and ended with a weight of 1350-1450 g 0.2-0.4 MY ago" (Evolution of the Human ASPM Gene, a Major Determinant of Brain Size (Genetics 2003))
The Human Accelerated Regions are being explored and allready a regulatory gene involved in the development is known to diverge by 18 nucleotides in a gene only 118 nucleotides long. There is no explanation for this naturally occuring and random mutations would be deleterious. The only way would be for the genetic mechanism for altering the amino acid sequence to be identified.
That's the primer but this thread has bounced around so much getting to the actual evidence doesn't likely. I'll give it some time but you don't seem to believe me when I tell you I am not the run of the mill creationist you are use to dealing with. No matter, let's see what you can do with this post.

This message is a reply to:
 Message 62 by Wounded King, posted 10-30-2006 3:11 AM Wounded King has replied

Replies to this message:
 Message 73 by Wounded King, posted 10-31-2006 2:50 AM eggasai has replied

  
eggasai
Inactive Member


Message 69 of 157 (359991)
10-30-2006 8:57 PM
Reply to: Message 66 by mick
10-30-2006 5:34 AM


Re: Eggasai is producing mashups of his previous posts.
quote:
thanks, that's good to know. Lahn's paper was actually based on a comparison of human and macaque, which represents 20-25 million years of evolution. But eggasai is cramming this number of mutations accumulating in 20-25 million years into the 7 million years separating chimp from human.
The study was not limited to macaques, he made broad comparisons:
"Human ASPM has 28 coding exons, spanning 62 kb in chromosome 1p31 and encoding a huge protein of 3477 amino acids (Fig 1). I determined the entire coding sequences of ASPM from one human, one chimpanzee, and one orangutan, and compared them in the phylogenetic tree of the three species" (Evolution of the Human ASPM Gene, a Major Determinant of Brain Size (Genetics 2003))
He has done a number of papers on the subject and since you are going by a news item it's no wonder you got confused.
quote:
Well, that's one problem solved isn't it?
Mick
You still haven't got the big picture here, the paper is available online, why don't you google it?

This message is a reply to:
 Message 66 by mick, posted 10-30-2006 5:34 AM mick has not replied

Replies to this message:
 Message 74 by Wounded King, posted 10-31-2006 3:00 AM eggasai has not replied

  
eggasai
Inactive Member


Message 70 of 157 (359993)
10-30-2006 9:03 PM
Reply to: Message 65 by Wounded King
10-30-2006 5:08 AM


Re: Eggasai is producing mashups of his previous posts.
quote:
I know I'm not Eggasai but the origins of some of these mistakes is obvious.
Nothing could be farther from the truth. You guys have not even bothered to read the paper the news release is based on. I would have been happy to provide quotes, citations and links early in the thread but I don't think I will now. The errors in this thread are appearing in virtually every post but most of them are not mine. You only made one correction that stood up to close scrutiny.

This message is a reply to:
 Message 65 by Wounded King, posted 10-30-2006 5:08 AM Wounded King has not replied

Replies to this message:
 Message 72 by Dr Adequate, posted 10-30-2006 10:25 PM eggasai has replied

  
eggasai
Inactive Member


Message 71 of 157 (359997)
10-30-2006 9:47 PM
Reply to: Message 64 by mick
10-30-2006 4:23 AM


Re: Getting the numbers right
quote:
Let's try this one more time
Ok, fine...
quote:
Okay, this time I will ask you questions and I'll try to keep everything clear. In return, perhaps you could answer the questions directly and keep personal insults to a minimum.
Sounds pretty reasonable.
quote:
Question: what do you mean when you say "hundreds if not thousands of mutations in hundreds if not thousands of genes"? My understanding is that the number of mutations being tallied here was measured across the whole genome, not just in the genes. Even if the mutations were measured only in coding sequences (which I do not recall is the case) that would still be tens of thousands of genes, not hundreds. Are we not talking about 40 million and nine mutations in the entire genome?
There are two issues here, one is the total amount of evolution going back 25mya and the divergance between chimpanzees and humans. You have to understand, a primate brain is roughly 3 times bigger then an ordinary mammals and the human brain is roughly 3 times bigger then an apes. The quote from the press release was just a little hyperbole to get your attention. I was hoping to get into the direct comparison of genes and Lahn has done several comparisons along those lines.
quote:
Question: under the assumption that mutations are distributed randomly, how many mutations per gene do you think these figures represent? Here are my calculations: About 1.5% of the human genome consists of protein-coding sequences (Reference). if the 40 million and nine mutations are distributed randomly, that gives us an expected number of 600,000 mutations in the coding portion of the genome. Since there are around 35,000 protein-coding genes in the human body (Reference), that gives us an expected number of 17 mutations per gene. Would you agree with this logic, and if not, why not? I know that the assumption of random distribution of mutations is not realistic, but I'd like to know if you agree with the ballpark figure of tens of mutations per gene rather than hundreds or thousands of mutations per gene.
First of all there are less then 20,000 genes, the 35,000 is from a rough estimate immediatly following the HGP initial sequence. Roughly 1% of the human genome is believed to code for proteins, there are another 3-4% that are funtionally important gene (outliers, regulatory genes, housekeeping genes). Most of the mutations that have a strong enough effect (3 out of 4) are going to be deleterious. You do see some of this in modern biology in the immuity system and other places. My guess is that there are transposable elements that have to be altered in order to adjust for viruses and such. That's just a guess but that is one of the things I am most curious about.
Mutations are truely random and most of them are the result of transcript errors. Remember when I was talking about the central dogma of biology being DNA-transcription-RNA-translation, that's why I brought it up. The DNA is transcribed and goes through various cell cycle stages where transcript errors are corrected or the cell dies. We can get into that later, what is important here is that transcript errors and a failure to correct them is what causes most mutations like the ones in you and me. The only way that they are inheritable is if the are germline mutations and the genome is most vulnerable in the early stages of development. That's why I brought up the cleavage stage, that's the time and place where major changes would have to be made.
quote:
Question: why 20 mutations per year? You have said that there were forty million and nine mutations. Forty million and nine divided by seven million is 5.7, not 20
What I said was that there were 145 Mb (million base pairs)that diverge between chimpanzees and humans. I gave 7 million years for that to happen and it comes to just over 20 bps per years as a mean average. There are 350,000 generations in that time when you estimate a generation at 20 years. The mutation rate is roughly (2x10^-8 which would be 2 for every 100,000,000 bps. This would come to about 120 bps per diploid generation and observed mutations is usually anywhere from 120 to 180bps. I won't get into the fixation rate now except to say they are rarely fixed in successive generations.
quote:
Question: what do you mean by "in their respective genomes"? The total number of mutations we are talking about here is the SUM of the mutations that have occurred either in the chimp lineage or in the human lineage. Just by comparing the chimp to the human, we cannot tell which lineage the mutations arose in. This is a minor point but I would like to know if you agree.
When we talk about 145 Mb we are talking about then split between the two genomes. The thing is that mutations happen during meiosis so there are two copies of the chromosomes so it stands to reason that there are twice the number of transcript errors. I understand what you are saying but it gets complicated when you are talking about whether the difference between the two genomes is the result of one geneome being altered or the other. I have a much simplier way of approaching it.
The chimpanzee genome paper looks at a side by side comparison of chimpanzee and human genomes. This gives us the divergance and it comes to about 16 million substitutions in the two genomes or 35 million nucletides measuring the total amount of divergance. There are about 45 million bases in each of the two genomes for a total of around 90 Mb. The chromosomal rearrangements are simply inversions, the chimpanzee goes 1,2,3... and the human seqment goes 3,2,1. The idea is that they simply flipped but the ones the Chimpanzee Genome Constortium looked at were as long as 4 Mb.
quote:
After we've sorted out these basic facts, I have some more questions to ask, if that's okay with you.
Thanks! I think short focussed posts like these will help the debate to move along nicely. I am happy to retract anything here if I've made a mistake so let's try to have a productive discussion.
Sounds good, I look forward to the next round of questions. If you like I can put together an annotated bibliography on the papers I am referancing. When you are looking at scientific literature it's not hard to make mistakes, scientists do it all the time. What is important is that what is clear should come front and center. I think it will help a lot if we took a good look at the Chimpanzee Genome paper and some of the comparisons they made.

This message is a reply to:
 Message 64 by mick, posted 10-30-2006 4:23 AM mick has not replied

Replies to this message:
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Dr Adequate
Member (Idle past 284 days)
Posts: 16113
Joined: 07-20-2006


Message 72 of 157 (360000)
10-30-2006 10:25 PM
Reply to: Message 70 by eggasai
10-30-2006 9:03 PM


Re: Eggasai is producing mashups of his previous posts.
I would have been happy to provide quotes, citations and links early in the thread but I don't think I will now.
Since you have been wrong about the contents of every paper you've cited, ceasing to cite papers might well be a smart move.
But then, you see, we shall have nothing to go on except the say-so of a guy who hasn't learnt the most basic facts of genetics.

This message is a reply to:
 Message 70 by eggasai, posted 10-30-2006 9:03 PM eggasai has replied

Replies to this message:
 Message 76 by eggasai, posted 10-31-2006 10:24 AM Dr Adequate has not replied

  
Wounded King
Member
Posts: 4149
From: Cincinnati, Ohio, USA
Joined: 04-09-2003


Message 73 of 157 (360029)
10-31-2006 2:50 AM
Reply to: Message 68 by eggasai
10-30-2006 8:43 PM


I've read the papers, now why not address the isssues I raised?
You seem to be confusing the inframe indels with the gross structural changes that would be required in the protein coding genes discussed in the Chromosome 22 paper.
Now why would I do that? Oh right, its beacuse you just said ...
"Taken together, gross structural changes affecting gene products are far more common than previously estimated (20.3% of the PTR22 proteins, as listed in Supplementary Tables 4 and 5)."
The International Chimpanzee Chromosome 22 Consortium, Nature 27 May 2004
These are inframe indels in protein coding genes, notice it's 20.3% of the ones on PTR22. Actually these are just differences in side by side comparision but when assuming a common ancestor it must have been an indel that produced it.
So in fact if ayone is making the confusion you just accused me of it was in fact you. You only just claimed in the previous post that all of those gross structural changes were in frame indels, do you see where I might have got the idea that that was what you thought?
I was talking here about the HAR1 regulatory gene, it's 118 nucleotides long and 18 of them diverge between chimps and humans. You are going off on somekind of a tangent here and making vauge references to a paper, maybe you should quote it at least.
You were talking about HAR1 again suddenly were you, OK. Why should anyone expect to see in frame indels in a non-coding region of a gene? I have been making this point repeatedly and you have yet to address it. The 118 nucleotide sequence does not functionally code for any amino acids, if anything its function appears to be mediated by the secondary structure of the resulting RNA transcript.
I'm not sure why you thought the reference was vague given that you were talking specifically about the chromosome 22 paper in the post I was replying to. I appreciate that you are having to keep track of a number of seperate conversations at once but it isn't hard back to trackback in these threads.
ou blew by my point about the mutation rate reguired for 145 Mb worth of divergance. That still comes to a mean average of 20 per year for 7 million years.
20 whats now? Is it nucleotides or mutations today? If it is mutations then as has been pointed out the figure is wrong. If it is nucleotides then, as has also been pointed out repeatedly, you are failing to take into account the many large scale mutations which can account for hundreds to millions of bases in one event.
Then it stops in modern times and levels off at 2x10-8 which it 2 per 100,000,000 nucleotides per diploid generation.
OK, for someone so keen to talk about how great his references are this is the sort of figure which could do with some evidentiary backing and also some rationale for why it makes any difference whatever to the matter under discussion. What is your evidence that anything has stopped or the the modern mutation rate has leveled off from something. I've seen similar rates quoted in some papers (Kondrashov, 2003) but it would help to know exactly what you are basing your figures on since they report similar rates estimated from the comparison of chimp and human pseudogenes. That paper itself estimates 'that the total number of new mutations per diploid human genome per generation is ~100'. Why do you consider these numbers insufficient?
I assume by your response that you either don't intend to look up the affects of mutations on functionally biased neural genes or you don't want to talk about them.
You mean I should do your work for you? I have repeatedly asked you to provide substantiation for your several claims that any mutation in such genes would be lethal despite the obvious counterevidence of the many mutations in such genes seen across different species. Given that it was your claim the onus is traditionally on you to provide some support for it.
Simply showing that there are lots of syndromes and genetic disorders related to such genes proves nothing other than that such disorders have significant phenotypes which are easily identified and are the subject of much medical attention.
You asked about the cleavage stage so I went ahead and linked you to a paper that showed a typical Darwinian picture of it.
A typical 'Darwinian' picture from ARN? You don't think that a site dedicated to the promulgation of intelligent design propaganda might not be the best place to go for a 'Darwinian' picture? Even so this doesn't explain why your quote and your reference had nothing to do with each other beyond both singularly failing to answer the actual question I asked, beyond making it clear that you meant embryonic cleavages.
You keep missing my points because you don't like going into the specifics.
I'm very happy to go into specifics, and when I have done just that in terms of papers you referenced and your argument you failed to reply to my posts. Sadly you seem to think that being able to pull a number out of a paper means you know what it means when your argument shows that this is not the case.
145 Mb diverge in 7 million years is far beyond the range of the observed mutation rate. It comes to 20 million nucleotides per year for 7 million years.
No, it doesn't. I'd shake your calculator and try again.
The physiological costs of the human brain growing from that of an ape is enormous and refutes Darwinian anagenesis scenerios completly
The costs are enormous, but I think there is clearly a case to be made that the substantial quantitative, if not qualitative, increases in our mental activities has had a clear positive effect on our ability to survive so the benefits may have been sufficienty greater than the costs. I don't see in the slightest how this conflicts with any evolutionary biology in an anagenetic model or otherwise.
There is no explanation for this naturally occuring and random mutations would be deleterious.
Demonstrate this to be the case, making the same claim over and over again does nothing but show the vacuity of your argument. Why would all random mutations be deleterious? If this is not the case then why wouldn't random mutation and a selective pressure favouring larger and more complex brains be sufficient, other than your simple desire to not believe it?
The only way would be for the genetic mechanism for altering the amino acid sequence to be identified.
Except the amino acid sequence doesn't have a tinker's cuss to do with the Har1 region since it is a non-coding gene!! And the genetic mechanisms leading to changes in amino acid sequence are well characterised, they are base pair substitutions and frame changing mutations of the kind we have been discussing all along. If you had actually addressed any of the vital failures you display in understanding the basic molecular genetics then this should now be obvious to you.
I'll give it some time but you don't seem to believe me when I tell you I am not the run of the mill creationist you are use to dealing with.
Perhaps that is because you behave in just the same way, using papers to support a claim for which they offer no support, using IDist websites as a reference, showing a failure to grasp the fundamental aspects of the biology we are discussing. I'm afraid these are creationist characteristics with which we are all too familiar.
If you want to show you break the mold then actually go back and look at what absolutely everyone else on this thread agrees is how the 'fundamental dogma' actually operates and ask yourself how we could all have got exactly the same wrong idea about it and only you understand how it really works.
TTFN,
WK
Edited by Wounded King, : Edited to expand commentary on mutation rates and add reference.
Edited by Wounded King, : Edited for formatting

This message is a reply to:
 Message 68 by eggasai, posted 10-30-2006 8:43 PM eggasai has replied

Replies to this message:
 Message 79 by eggasai, posted 10-31-2006 12:41 PM Wounded King has replied

  
Wounded King
Member
Posts: 4149
From: Cincinnati, Ohio, USA
Joined: 04-09-2003


Message 74 of 157 (360033)
10-31-2006 3:00 AM
Reply to: Message 69 by eggasai
10-30-2006 8:57 PM


Re: Eggasai is producing mashups of his previous posts.
Ummm, isn't that actually a completely different paper than the one we were talking about?
Yup, I'm pretty sure we were talking about the..
hundreds if not thousands of mutations in perhaps hundreds or thousands of genes
Which was from the press release to the 2004 cell paper. So what does a paper from the previous year on ASPM have to do with anything?
He has done a number of papers on the subject and since you are going by a news item it's no wonder you got confused.
YOu do remember referencing that 'news item' right at the start in your opening post I hope. You were happy enough to make it the basis of your 2nd 'main point'.
Or would you identify the basis of your 'hundreds if not thousands...' rhetoric, if it is not from the quote from Lahn?
You still haven't got the big picture here, the paper is available online, why don't you google it?
Sheesh enough with the google already, we are all quite capable of using pubmed. Perhaps if you didn't use google to turn up your references you wouldn't end up with press releases and ARN articles.
TTFN,
WK

This message is a reply to:
 Message 69 by eggasai, posted 10-30-2006 8:57 PM eggasai has not replied

  
Wounded King
Member
Posts: 4149
From: Cincinnati, Ohio, USA
Joined: 04-09-2003


Message 75 of 157 (360044)
10-31-2006 6:18 AM
Reply to: Message 71 by eggasai
10-30-2006 9:47 PM


Where and when need these mutations occur?
The thing is that mutations happen during meiosis so there are two copies of the chromosomes so it stands to reason that there are twice the number of transcript errors.
Eh? You only just finished telling me that mutations needed to happen during early embryonic cleavage stages and now this has changed to during meiosis? If it was meiosis you meant why did you post references to embryonic cleavages in response when I asked you if you were talking about mitosis, meiosis or embryonic cleavages?
It also stands to reason that while there might be 2 times as many 'transcript' errors, whatever they are, per cell there would not be 2 times as many per diploid genome. Also why single out meiosis since there is a duplication of the chromosomes during mitosis as well.
Could you try and give us a coherent idea of where and when you think these mutations must arise, and why?
In normal biology a mutation can arise at any time and as long as it occurs somewhere within the germline lineage it may be inherited. The mutation could be as early as the 2 or 4 cell stage and lead to a mosaicism encompassing the germ cells. The mutation might occur, as you suggest, during meiosis and be present in only one of the millions of gametes produced.
What exactly are you trying to say?
Are you getting transcription confused with DNA replication because except in very exceptional circumstances mRNA transcripts are not re-incorporated into the genome and consequently neither would mistranscribed sequences.
The single-stranded state of unwound DNA during transcription does seem to be more susceptible to certain mutations (Huson et al, 2003), is this perhaps what you were thinking of? Admittedly that work was on Salmonella and research on mammals has produced differing results some suggesting an increase (Bachl et al., 2001) and some a decrease (Lippert et al., 1998) in mutation rates associated with transcription.
TTFN,
WK

This message is a reply to:
 Message 71 by eggasai, posted 10-30-2006 9:47 PM eggasai has not replied

  
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