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Author Topic:   Genetics and Human Brain Evolution
eggasai
Inactive Member


Message 42 of 157 (359544)
10-28-2006 7:07 PM
Reply to: Message 33 by RAZD
10-28-2006 8:45 AM


Maybe I should stay out of this.
quote:
No, it's more than a cliche that scientists use evidence to back up their theories. Creationists however love to ignore evidence and pretend they can keep repeating the same position no matter how much evidence is given that refutes it.
The Talk Origins shelf of skulls gives the illusion of a gradual anagenesis of the human skull. Homo habils had a cranial capacity just over 500cc while the Austropithecines are thought to have averaged above 400cc. The period from at least 5 mya until under 2 mya represents a prolonged period of stasis with about a 200cc variance not counting dimorphic variables. Homo habilis was most likely contemporary with Turkana Boy or only seperated by a couple of hundred thousands years. Turkana Boy weighs in at a cranial capacity above 900cc and Homo erectus cranial capacity remains static for at least 1 million years.
Now, if you would like to take a walk through the shelf of skulls I would be delighted to debunk this optical illusion with substantive details. By the way, Homo rudolfensis was originally dated 3 million years old and only moved because Homo habilis was 200cc smaller. The dates assigned are obviously bogus but given what you listed, this one is a no brainer (LOL I'm so punny ). Everything from A to F is an ape, everything from G to you and me are humans.
What Talk Origins fails to clarify is that the human brain is three times that of a chimpanzee.
quote:
... is in the middle of the transitions from Australopithecus africanus to modern human.
Then you should be able to tell me both the species, cranial capacity and speciman catalogue ID. I say it's either ape or human, what is your criteria for determining it is a transitional?
quote:
You haven't addressed the issue of sexual selection that allows faster adaptations for run-away features than for normal features, and the only argument you have is your personal incredulity that what we see in genetics and in fossil evidence could not have happened naturally.
On the contrary, I have the Chimpanzee Genome Consortioums conclusion that natural selection was not a factor in the evolution of humans from the last common ancestor of chimps and humans. I have the selective coefficients from the divergance between human and chimpanzee genomes. I have the comparative anatomy of contemporary chimanzee and human morphological traits to use as a based line. Finally I have the divergance of the respective genomes and the observed mutation rate for hominids, the fixation rate and the deleterious effects of mutations on protein coding and functional genes.
I am far from incredulous and I'm immune to these Darwinian rethorical devices. The discussion can focus on circular arguements over semantical hair spliting but I'm not chasing it.
I have an idea, why don't you guys just correct the errors in one anothers posts and I'll jump back into the discussion when your done.
Edited by eggasai, : I wanted to rephrase something

This message is a reply to:
 Message 33 by RAZD, posted 10-28-2006 8:45 AM RAZD has replied

Replies to this message:
 Message 48 by Dr Adequate, posted 10-29-2006 1:55 PM eggasai has replied
 Message 60 by RAZD, posted 10-29-2006 9:54 PM eggasai has not replied

  
eggasai
Inactive Member


Message 43 of 157 (359546)
10-28-2006 7:23 PM
Reply to: Message 41 by Wounded King
10-28-2006 6:47 PM


Re: Fundamental Biology Question
quote:
A sequence of nucleotides is not a single nucleotide.
Like I said, let me know when you guys are interested in discussing genetics and the human brain.

This message is a reply to:
 Message 41 by Wounded King, posted 10-28-2006 6:47 PM Wounded King has not replied

  
eggasai
Inactive Member


Message 50 of 157 (359694)
10-29-2006 5:27 PM
Reply to: Message 46 by mick
10-29-2006 1:00 AM


Re: some data and arguments on brain sizes in primates
quote:
A plot of absolute cranial capacity over time, data drawn from every hominin skull found prior to 2000, shows precisely the opposite. Whether you consider these skulls to be part of the genus Homo or part of another extinct group of apes, there is no decrease over time in absolute cranial volume.
Homo rudolfensis KNM-ER 1470 was originally dated 3 million years old which would make it older then the australopithecines. It had to be moved up a million years because it didn't fit into the anagenesis of Darwinian naturalistic a priori assumptions.
quote:
No, the skulls are placed in the "family tree" based on phylogenetic analysis of hundreds of morphological characteristics.
They are placed in the chart in such a way as to give the illusion of anagenesis. What you are calling a phylogenetic analysis is really Darwin's tree of life revisted. It is an a priori assumption that has no genuine frame of referance.
quote:
eggasai writes:
There is no genuine absolute brain/body size ratios
That's a good point, but since we don't have any bodies with tissues we have little choice but to infer body mass if we want to talk about these issues. A variety of hominid and ape body mass models can be used; they are able to predict (imprecisely but reasonably) the body mass of extant apes; and they all give pretty similar results in terms of the general trend in encephalization. One might also calculate an encephalization quotient based on the correlation between cranial capacity and some other measurable skeletal variable, but I can't find an example of that having been done and I foresee difficulties because craniodental characters will be functionally correlated as well as correlated by body mass allometry.
You are trying to use a very precise measurement and apply it to skulls that are often crushed, fragmented and dated using highly subjective criteria. Cranial capacity represents a cerebral rubicon that marks a clear line of demarkation in the transition from ape to humans. The genetic basis for such a morphological innocation simply does not exist.
"We’ve proven that there is a big distinction. Human evolution is, in fact, a privileged process because it involves a large number of mutations in a large number of genes,” Lahn said.
“To accomplish so much in so little evolutionary time”a few tens of millions of years”requires a selective process that is perhaps categorically different from the typical processes of acquiring new biological traits.”
Generally speaking, the higher up the evolutionary tree, the bigger and more complex the brain becomes (after scaling to body size). But this moderate trend became a huge leap during human evolution. The human brain is exceptionally larger and more complex than the brains of nonhuman primates, including man’s closest relative, the chimpanzee.
One way to study molecular evolution is to examine changes of when and where proteins are expressed in the body. “But there are many challenges to studying the evolution of protein expression. Instead, we chose to track structural changes in proteins,” said graduate student Eric Vallender, lead author of the article along with former graduate student Steve Dorus, who both work with Lahn.
The researchers examined the DNA of 214 genes involved in brain development and function in four species: humans, macaques (an Old World monkey), rats and mice. (Primates split from rodents about 80 million years ago; humans split from macaques 20 million to 25 million years ago; and rats split from mice 16 million to 23 million years ago.)"
http://chronicle.uchicago.edu/050106/lahn.shtml
quote:
You are still using absolute brain volumes, and this is statistically unsound because you are ignoring a known fact that brain size is a covariate of body size. Consider the body mass and endocranial volume of two Homo habilis individuals and the mean values for a few other apes.
No I'm not, I'm making a very specific inferance based on what science is telling us about this supposed transitional. The brain would have had to triple in size in about 1.5 million years from Homo habilis 510cc and modern humans 1350cc. This become increasingly ridiculas when you look at the actual genes involved. Do you realize that most of the neural genes would require in-frame indels of considerable length. Brain genes are amoung the most highly conserved genes in the human body, a close second would be the liver which would have underwent intense adaptive evolution as well. Random mutations plus natural selection are obviously not going to get you where there. Relaxed funtional constrait does not make any sense because of the deleterious effects. Then there is the fact that these would have to be germline mutations during the cleavage stage and it is here that mutations are least likely to occur.
Now you can use all the scattergrams and tree like charts you like. The genetic basis such such a morphological giant leap does not exist except in the mind of Darwinians.
quote:
Although the brain volume of female Homo habilis is of the same order of magnitude as the male Gorilla, the habilis body mass is about five times smaller. Similarly, although the body mass of female Homo habilis is of the same order of magnitude as the female Bonobo, the habilis brain volume is half as large again. What does this signify?
What you are doing here is pouring the concrete before the frame is ready. EQ is fine for making precise measurements but we really don't have those from prehistory, for one thing the dates are highly subjective. That said, do you really think it makes sense to compare Homo habilis (actually an austropithcine if you mean OH62) to a gorilla? Why don't you do you little formula for a chimpanzee? I think you will find that Homo habils is just a little bigger.
quote:
It is this difference in the allocation of resources to the brain versus elsewhere that is of evolutionary interest. The absolute values are of little interest because natural selection is acting on the trade-off over allocation of limited resources, not on absolute magnitude. Sure, big animals have access to greater resources and can grow larger arms, legs, fingers and brains. But such an increase in absolute brain growth tells us little about the evolution and energetics of brain development.
You can't compare the adaptation of a limb to the complete overhaul of neural genes, it has no rational basis:
"“The making of the large human brain is not just the neurological equivalent of making a large antler. Rather, it required a level of selection that’s unprecedented,” Lahn said. “Our study offers the first genetic evidence that humans occupy a unique position in the tree of life. Simply put, evolution has been working very hard to produce us humans.” " (from the article linked above)
quote:
The absolute values are of little interest because natural selection is acting on the trade-off over allocation of limited resources, not on absolute magnitude.
The absolute values are of paramount importance whether they interest you or not. They are crucial because your explanation of natural selection would not have been a big factor.
"Although it is more difficult to quantify the expected contributions of selection in the ancestral population, it is clear that the effects would have to be very strong to explain the large-scale variation observed across mammalian genomes. There is tentative evidence from in-depth analysis of divergence and diversity that natural selection is not the major contributor to the large-scale patterns of genetic variability in humans." (Chimpanzee Genome Consortium, Nature 2005)
Charles Darwin when he wrote On the Origin of Species proposed that natural selection was the primary mechanism for adaptive evolution. In this day and age it's the first thing the evolutionists use to explain a major mophological adaptation. How did we get here? Darwin's On the Origin of Species is just one long arguement against 'special creation'. It's not a genetic mechanism, it's rethoric used as a dialectical tool meant to seperate people from belief in 'special creation', nothing more.
Want to show me I'm wrong, no problem. Let's take a walk through that actual scientific research. We can look at the Chimpanzee Genome paper, some of Bruce Lahn's work and the allometry of Asian Homo erectus skulls compared to modern Chinese. I'm telling you before we start, the transtion from Homo habilis to Homo erectus didn't happen and the evidence is telling us exactly that.
Edited by eggasai, : transcript error having a deleterious effect on my post

This message is a reply to:
 Message 46 by mick, posted 10-29-2006 1:00 AM mick has not replied

Replies to this message:
 Message 51 by Dr Adequate, posted 10-29-2006 5:50 PM eggasai has not replied
 Message 52 by Wounded King, posted 10-29-2006 5:59 PM eggasai has replied

  
eggasai
Inactive Member


Message 53 of 157 (359701)
10-29-2006 6:17 PM
Reply to: Message 48 by Dr Adequate
10-29-2006 1:55 PM


Re: Maybe I should stay out of this.
On the contrary, I have the Chimpanzee Genome Consortioums conclusion that natural selection was not a factor in the evolution of humans from the last common ancestor of chimps and humans.
quote:
You have no such thing.
"Although it is more difficult to quantify the expected contributions of selection in the ancestral population, it is clear that the effects would have to be very strong to explain the large-scale variation observed across mammalian genomes. There is tentative evidence from in-depth analysis of divergence and diversity that natural selection is not the major contributor to the large-scale patterns of genetic variability in humans." (Chimpanzee Genome Consortium, Nature 2005)
Maybe you should read my posts and the scientific literature a little more carfully.
Edited by eggasai, : Transcript error

This message is a reply to:
 Message 48 by Dr Adequate, posted 10-29-2006 1:55 PM Dr Adequate has replied

Replies to this message:
 Message 54 by Dr Adequate, posted 10-29-2006 6:26 PM eggasai has not replied

  
eggasai
Inactive Member


Message 55 of 157 (359703)
10-29-2006 6:54 PM
Reply to: Message 52 by Wounded King
10-29-2006 5:59 PM


"natura non facit saltum"
"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.
quote:
This is a very strange way to think of things, it is more usual to talk of conservation with a particular group of organisms such as the mammals or vertebrates. Being conserved within the human body just suggests that they aren't likely candidates for somatic mutation. This also seems directly contradicted by a lot of the evidence you yourself have shown showing that many neural genes have been subject to mutation and in many cases apparently to very strong selection leading to many more changes than might be expected under neutral selection.
What it contradicts is the a priori predictions of Darwinians who expected anagenesis progressions rather then a major overhaul of protein coding genes. 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.
quote:
This only seems obvious to you, and you have yet to produce a scrap of reasoned argument why anyone should accept your contention.
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.
quote:
You have produced no evidence to suggest that any of the difference between human genes and their highly conserved counterparts in other species have a deleterious effect. Your argument also seems to fail through basic logic. A relaxation of functional constraint by its very nature means that there are more possible non-deleterious mutations possible.
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.
quote:
What is this supposed to mean? Why should mutations occur during cleavage? I assume you mean cleavage during mitosis or meiosis rather than an embryonic cleavage stage but the reasoning behind your statement escapes me.
"The diversity of the earliest stages of development, here illustrated strictly within the vertebrates, provides one of the strongest challenges to the neo-Darwinian conception of homology and macroevolution. Given the hierarchical, step-wise logic or "architecture" of animal development, early stages such as cleavage and gastrulation lay the groundwork for all that follows. Body plan structures in the adult, for example, trace their cellular lineage to these early stages. Thus, if macroevolution is going to occur, it must begin in early development. Yet it is precisely here, in early development, that organisms are least tolerant of mutations. Furthermore, the adult homologies shared by these vertebrates commence at remarkably different points (e.g., cleavage patterns). How then did these different starting points evolve from a common ancestor?"
http://www.arn.org/docs/odesign/od182/hobi182.htm

This message is a reply to:
 Message 52 by Wounded King, posted 10-29-2006 5:59 PM Wounded King has replied

Replies to this message:
 Message 57 by Dr Adequate, posted 10-29-2006 7:11 PM eggasai has not replied
 Message 62 by Wounded King, posted 10-30-2006 3:11 AM eggasai has replied

  
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

  
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

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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:
 Message 75 by Wounded King, posted 10-31-2006 6:18 AM eggasai has not replied
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eggasai
Inactive Member


Message 76 of 157 (360090)
10-31-2006 10:24 AM
Reply to: Message 72 by Dr Adequate
10-30-2006 10:25 PM


Re: Eggasai is producing mashups of his previous posts.
I've been doing this for a couple of years and probably corrected more errors in this thread then I have that entire time. I've never seen so many basic misconceptions and the papers have not been quoted, cited are linked in any of your posts. You don't seem to be doing anything other then tell me I'm wrong which is nothing more then ad hominem rethoric.

This message is a reply to:
 Message 72 by Dr Adequate, posted 10-30-2006 10:25 PM Dr Adequate has not replied

  
eggasai
Inactive Member


Message 79 of 157 (360125)
10-31-2006 12:41 PM
Reply to: Message 73 by Wounded King
10-31-2006 2:50 AM


Re: I've read the papers, now why not address the isssues I raised?
quote:
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.
So you respond with this little quip...
quote:
Now why would I do that? Oh right, its beacuse you just said ...
I know what the problem is, you don't know what a reading frame is.
Those are the protein coding genes, a gross stuctural change is nothing more then 20% of the protein coding genes are much more different then predicted.
quote:
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.
That's exactly right and your problem would be...?
quote:
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?
An indel is just a mutation of length and a reading frame is just the the amino acid sequence. You seem to think that a reading frame is like the rack on a pool table that puts the balls in a triangle. It's not and until you start to realize that this is just a difference in the amino acid sequence you are going to keep correcting me based on your own misconception.
quote:
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.
You don't realize that the regulatory genes come in amino acid sequences do you? When 18 nucleotides diverge that means that at least 6 amino acids are different. The nucleotides don't code for anything, the amino acid sequences are the code for proteins.
quote:
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.
I don't really need to look back, it's just been one misconception after another. It would be nice if you guys were intent on actually correcting errors instead of unanimously contradicting me, whether I'm right or not.
quote:
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.
What that counts is 35 million single nucleotide substitutions, those are the only ones measured in nucleotides. The indels and chromosomal rearrangements are measured in base pairs. Now as far as mutations that involve in hundreds of millions of base pairs or nucleotides then I want to see it. Technically, the chromosome 2 fusion would not even be considered a mutation since the sequence didn't actually change.
Just in case you really are on to something here, tell me about the indels that mark the divergence between humans. In comparing the genomes of chimpanzees and humans the indels out numbered the indels as measured in base pairs. Does that hold true for human divergence?
quote:
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?
Because it would require 20 mutations (counting the rearrangements) per year for 7 million years. The mutation rate observed has a lot of variables but it's not the hundreds of mutations that would have had to be fixed. Much, if not most, of the divergence is fixed between humans and chimpanzees. If you don't like 2x10^-8 then try another one that adequetly fits the divergence. Let me guess, you think 400 base pairs diveging between the two genomes per generation is no big deal right?
quote:
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.
Oh really? Here is a list of known effects from mutations that involve genes in the human neural system:
Chromosomal translocations fusing the BCL6 gene to different partner loci are recurrent in primary central nervous system lymphoma and may be associated with aberrant somatic hypermutation or defective class switch recombination
"The transcription factor SOX2 is expressed most notably in the developing CNS and placodes, where it plays critical roles in embryogenesis. Heterozygous de novo mutations in SOX2 have previously been associated with bilateral anophthalmia/microphthalmia, developmental delay, short stature, and male genital tract abnormalities."
Mutations within Sox2/SOX2 are associated with abnormalities in the hypothalamo-pituitary-gonadal axis in mice and humans.
"Neurodegenerative disorders affecting the central nervous system, such as Alzheimer's disease, Parkinson's disease, Huntington's chorea (HD) and amyotrophic lateral sclerosis are characterized by the loss of selected neuronal populations. Another striking feature shared by these diseases is the deposition of proteinaceous inclusion bodies in the brain, which may be intracytoplasmatic or intranuclear, or even extracellular. However, the density and prevalence of aggregates are not always directly related to neurodegeneration. Although some of these diseases are the result of mutations in known proteins, with HD a clear example, the expression and location of the affected protein do not explain the selective neurodegeneration."
Cellular and molecular mechanisms involved in the selective vulnerability of striatal projection neurons in Huntington's disease.
The physiological costs are enormous because the deleterious affects are devastating. The genes with a functional bias involved in neural development do not respond well to mutations. Yet, it is exactly here that adaptive evolution must develop the size and complexity that became the human brain. One thing is certain, random mutations would be deleterious most of the time and a beneficial affect from one has yet to be observed in the human brain.
Edited by eggasai, : transcript errors

This message is a reply to:
 Message 73 by Wounded King, posted 10-31-2006 2:50 AM Wounded King has replied

Replies to this message:
 Message 80 by kuresu, posted 10-31-2006 12:48 PM eggasai has replied
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eggasai
Inactive Member


Message 81 of 157 (360147)
10-31-2006 1:54 PM
Reply to: Message 77 by sfs
10-31-2006 11:09 AM


Re: Getting the numbers right
Hey Steve, I wasn't able to get on CF so I've been hanging out here. At any rate, you wanted to correct something.
quote:
And I very much doubt that taking a good look at the chimpanzee genome paper will do any good. Assuming you're Mark Kennedy, and not merely someone copying his arguments and his prose style, then we've already been through the chimpanzee genome paper at great length over on Christian Forums, and you're still making the same mistakes about it.
Like counting all of the base pairs in the indels and applying them to the mutation rate as measured in base pairs.
quote:
Regardless of whether you're Mark or not, you're making numerous mistakes. Probably the most important one is trying to compare the mutation rate (as measured in modern humans) for single-base substitutions with the total number of bases mutated (from all kinds of mutation) in the comparison of humans and chimpanzees. You can't compare the rate of mutation events with the total number of bases changed in mutations, at least not if you want to do anything sane.
So it's insane to measure a mutation by the number of base pairs involved? Like I keep trying to tell you, they should be measured in base pairs. The average indel is something like 300 bps, your trying to tell me that every generation there was at least one fixed along with 5 single nucleotide substitutions. I'm pretty much convinced that the only mistake I'm making is introducing myself as a creationist.

This message is a reply to:
 Message 77 by sfs, posted 10-31-2006 11:09 AM sfs has replied

Replies to this message:
 Message 85 by sfs, posted 10-31-2006 2:28 PM eggasai has replied

  
eggasai
Inactive Member


Message 82 of 157 (360149)
10-31-2006 2:05 PM
Reply to: Message 80 by kuresu
10-31-2006 12:48 PM


Re: I've read the papers, now why not address the isssues I raised?
Ain't got none and he's not the first geneticist I've ran into in cyberspace.
"An open reading frame or ORF is any sequence of DNA or RNA that can be translated into a protein. In a gene, ORFs are located between the start-code sequence (initiation codon) and the stop-code sequence (termination codon). ORFs are usually encountered when sifting through pieces of DNA while trying to locate a gene. Since there exist variations in the start-code sequence of organisms with altered genetic code, the ORF will be identified differently. A typical ORF finder will employ algorithms based on existing genetic codes (including the altered ones) and all possible reading frames."
Open reading frame - Wikipedia
That's the point, nothing about this is all that mystical. The open reading frame is simply an amino acid sequence that can be translated into a protein. What is more a regulatory gene, unless I'm greatly mistaken. comes in amino acid sequences.

This message is a reply to:
 Message 80 by kuresu, posted 10-31-2006 12:48 PM kuresu has not replied

  
eggasai
Inactive Member


Message 87 of 157 (360172)
10-31-2006 3:10 PM
Reply to: Message 83 by sfs
10-31-2006 2:08 PM


Re: I've read the papers, now why not address the isssues I raised?
quote:
He doesn't realize it because it isn't true. The regulatory gene in question, HAR1, does not code for any amino acids -- it's an RNA gene that is never translated into protein. (And a sequence of amino acids does not code for a protein; a sequence of (bonded) amino acids is a protein.)
Ok, so the triplet codons in regulatory genes don't code for amino acids. A single nucleotide substitution is different from a single nucleotide polymorphism and an indel a million bps long counts as one mutation.
Just tell me something, does it give you pause when you see a regulatory gene with 18 nucleotides that divergen between chimpanzees and humans? I mean especially when chickens and chimps only diverge by two and their LCA lived 310 mya.
Let me guess, it doesn't supprise you one bit.
quote:
Base pairs are pairs of nucleotides. What are you talking about here?
Just what I said, single nucleotide substitutions and indels measured in base pairs.
quote:
I have no idea what this question is supposed to mean.
If you were to take all of the mutations in your personal genome and that measured them in single nucleotide/base pair increments, would the single nucleotides substitutions be greater or lessor in your genome?
quote:
No, it would not require 20 mutations per year; it would require 20 mutated nucleotides (including indels) per year. Those 20 mutated nucleotides occur in ~5 mutations per year. (And that's including mutations in both chimps and humans.)
So you have one indel 300+ bps plus 5 single nucleotide substitutions in your genome that you will, of did, pass onto your offspring in as a permenant fixture in their genomes?
quote:
I don't know about anyone else, but I certainly think it's no big deal
I think it is a very big deal since the mutation rates I am looking at measure mutations by the base pair, not by mutational events. I am also suspect that the accumulated single nucleotide substitutions outweigh indels in length as measured in base pairs. Finally, I think most, if not virtually all the transcript errors in the germline cells are repairable in successive generations.
What is really important here is that even if you are totally convinced that the divergance in the two genomes are accounted for by the observed mutation rate, it does not account for the human brain.

This message is a reply to:
 Message 83 by sfs, posted 10-31-2006 2:08 PM sfs has replied

Replies to this message:
 Message 88 by sfs, posted 10-31-2006 3:51 PM eggasai has not replied

  
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