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Author Topic:   Genetics and Human Brain Evolution
eggasai
Inactive Member


Message 1 of 157 (234687)
08-18-2005 9:44 PM


I am new to the boards and I am interested in discussing the genetic basis of human evolution. I am specificlly interested in the evolution of the human brain over the last 2 1/2 million years. There are three main points of discussion I am proposing:

1.The genetic changes involved in the acquisition of unique human features, such as highly developed cognitive functions, bipedalism or the use of complex language.

http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v429/n6990/full/nature02564_fs.html

They have compared the differences betwee the human genome and that of chimpanzees, these differences, attributed to mutations, can be reduced to ratios. Bear this in mind when looking at real world genetic research into comparisons of humans (homo sapiens) and our, supposedly, closest relative the chimpanzee.

2. The genes involved and the number of changes that would be required for humans to evolve from apes.

http://www.eurekalert.org/pub_releases/2004-12/hhmi-eth122804.php

One of the study's major surprises is the relatively large number of genes that have contributed to human brain evolution. "For a long time, people have debated about the genetic underpinning of human brain evolution," said Lahn. "Is it a few mutations in a few genes, a lot of mutations in a few genes, or a lot of mutations in a lot of genes? The answer appears to be a lot of mutations in a lot of genes. We've done a rough calculation that the 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."

3. The genetic basis for the three-fold brain expansion over ~ 2 million years.

http://www.genetics.org/cgi/content/abstract/165/4/2063

No amount of random combinations of chimpanzee genes could ever produce such a change in size and complexity. The only way it could happen is thousands of mutations in thousands of genes.

I proposed this in another forum and someone suggested I try here. I await your response to my proposal of a new topic of discussion.

This message has been edited by eggasai, 08-18-2005 09:46 PM


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AdminNosy
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Posts: 4754
From: Vancouver, BC, Canada
Joined: 11-11-2003


Message 2 of 157 (234692)
08-18-2005 10:03 PM


Thread moved here from the Proposed New Topics forum.

  
New Cat's Eye
Inactive Member


Message 3 of 157 (234708)
08-19-2005 1:23 AM
Reply to: Message 1 by eggasai
08-18-2005 9:44 PM


3. The genetic basis for the three-fold brain expansion over ~ 2 million years.

I apologize in advance for not looking at even one of your links, but this statement reminded me of a book I read.

Ever heard of Fingerprints of the Gods?

I read it, it was awesome and well written. One of the main points is that humans are very very old.

This is the author's main website. I haven't explored it that much.

But anyways, the basis for your idea is that humans are older than they seem and this book could help you out.

This message has been edited by Catholic Scientist, 08-19-2005 12:24 AM


This message is a reply to:
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NosyNed
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Posts: 8868
From: Canada
Joined: 04-04-2003
Member Rating: 7.2


Message 4 of 157 (234710)
08-19-2005 1:50 AM
Reply to: Message 1 by eggasai
08-18-2005 9:44 PM


Numbers of mutations
The answer appears to be a lot of mutations in a lot of genes. We've done a rough calculation that the 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."

The numbers here should be considered in the correct context.

There are right now something between 10 billion and 50 billion new mutations in the human population. That is roughly the number of mutations that the living human population has.

I think we can put an upper limit on the number neede too rather than use a "conservative estimate". If we take humans as being 98% the same as chimps in their genomes and say all of that 2% is for the brain (obviously to high) we get 2% of 3 x 10**9 base pairs different (I think) which is at the very highest about 60 million differences.

This took about 6 million years (to make the numbers easy and ignoring that chimps have been changing too) that means we need 10 useful mutations a year in a population of a few 1,000 individuals. This is at the very worst and is waaay over a realistic number.

If you really want to get a feel for how possible it is you should look into the genetics that we are beginning to get a handle on.

From "Genome" by Matt Ridley

This is discussing different personalities, in particular those who are more adventure seeking and those who are not.

quote:
The first genetic difference turned up... in the D4DR gene on chromosome 11. D4DR has a variable repeat sequence in the middle, a minisatillite phrase 48 letters in length repeated between two and 11 times. Most of us have four or seven copies of the sequence, but some people have two, three, five, six, eight, nine, ten or eleven. The larger the number of repeats, the more ineffective is the dopamine receptor at capturing dopamine. A 'long' D4DR gene implies a low responsiveness to dopamine in certain parts of the brain, whereas a 'short' D4DR gene implies a high responsiveness.

Hamer... wanted to know if people with the long gene had different personalities from people with the short gene.

...

-- people (in a small sample) with either one or two long copies of the gene... were distinctly more novelty seeking than people with two short copies of the gene.


In addition, see Message 1

The size of the brain is influenced (Ridley warns against assuming this one gene is the whole answer) by the number of repeats of of a 75 letter sequence. If this kind of thing applies in other places then a reasonably simple mutations (like a mistaken extra copy of 75 letters) can have profound influences.

The idea that mutations can not supply the changes needed to give a larger more complex brain is made to look pretty shakey by such discoveries.


This message is a reply to:
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eggasai
Inactive Member


Message 5 of 157 (357492)
10-19-2006 3:09 PM
Reply to: Message 3 by New Cat's Eye
08-19-2005 1:23 AM


Chimpanzee genome
quote:
One of the main points is that humans are very very old.

I know who Francis Collins is, he is the head of the Human Genome Project. I heard him discussing his new book on NPR, he left out some pretty important facts. First of all, the Chimpanzee Genome Project published the intitial seqeunce back in September of 2005. The found that the genomes of Chimpanzees and Humans was not 98%-99%, it was closer to 95%. What difference does that make? When you add up the single nucleotide substitutions, indels and chromsomal rearrangements it comes to 145 million base pairs. For these differences to have to accumulate would require 20 nucleotide fixed in the respective genomes, on average,for 7 million years. When Nature announced the publication of the Chimpanzee Genome they again said that 98% of the DNA was the same. There is just one problem with this, the paper says that single base substitutions (35Mb) are 1.29% and that they are dwarfed by the indels (90Mb)which are 3%-4%. With the mutation rate being about 2 * 10^-8 that means about 123 germline mutations per zygote.

Don't believe me? Type 'chimpanzee genome' into your google search engine and the page announceing the paper will be at the top of the list. Then look up the Initial Sequence of the Chimpanzee Genome' (free online) and look up the indels. I would have loved it if Francis Collins had explained how this is possible but I doubt seriously he will.

The human brain is 3 times the size of Chimpanzees, I don't think I will get any arguements to the contrary. Recently they started studying the Human Accelerated Regions, there are 49. The first one uncovered a regulatory gene involved in the developement of the cerbral cortex. When the human gene, 118 nucleotides long, was compared to the chimpanzee counterpart there were 18 substitutions. When the chimpanzee gene was compared to that of a chicken there were 2 substitutions. Chimps and chickens a believed to have a common ancestor 310 million years ago. The question arises how does such a highly conserved gene suddenly aquire 18 substitutions?

Francis Collins is one of the world's leading genetic researchers, I would love to hear him explain this.


This message is a reply to:
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Replies to this message:
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Wounded King
Member (Idle past 2433 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


Message 6 of 157 (357676)
10-20-2006 9:21 AM
Reply to: Message 5 by eggasai
10-19-2006 3:09 PM


Genes affecting brain development
What difference does that make? When you add up the single nucleotide substitutions, indels and chromsomal rearrangements it comes to 145 million base pairs. For these differences to have to accumulate would require 20 nucleotide fixed in the respective genomes, on average,for 7 million years.

It is important to bear in mind that fixation of a single indel could easily account for more than 100KB of difference.

Other than your incredulity at the rapid evolution of the Har1 gene in the human lineage (Pollard et. al, 2006) you don't really seem to be making an argument here. You are bringin up lots of data but you seem to think that this alone is a substitute for a coherent statement.

You say you want a discussion but your OP doesn't really provide anything to discuss.

The one discursive point you have raised is how Har1 has evolved so rapidly in humans. The obvious answer would be that the gene was subject to some selective pressure which favoured its divergence from the conserved sequence, either that or it was released from some strongly stabilising negative selective pressure.

The paper mentions that the bias of substitutions from W(A or T )->S(C or G) may be linked to their position in the chromosome or possibly to selection for higher levels of expression. This may be connected to the different levels of Har1F and Har1R which the study observes in humans but not in mice.

As the paper mentions there are a number of other genes involved in brain development which have similarities in terms of being subject to strong positive selection and in terms of showing conserved patterns of expression but apparent functional differences. One example they mention is ASPM research on which you previously referenced.

What makes you think that there is a problem with mutations in such genes being responsible for the enlargement and other changes we see between human and chimpanzee brains?

TTFN,

WK


This message is a reply to:
 Message 5 by eggasai, posted 10-19-2006 3:09 PM eggasai has responded

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eggasai
Inactive Member


Message 7 of 157 (358194)
10-22-2006 8:28 PM
Reply to: Message 6 by Wounded King
10-20-2006 9:21 AM


Re: Genes affecting brain development
I didn't say kilobases I said megabases and one of hte chromsomal rearrangements is 4 Mb long. The observed mutation rate hovers around 2.5 x 10^-8 which comes to 173 germline mutations per diploid generation. 145 Mb in 7 million years comes to 20 per year, fixed withing the respective genomes for 7 million years. That's not just an arguement, it's double the mutation rate estimated for several decades now. When the divergance was thought to be 99% the mutation rate dovetailed nicely but now it is impossible.

All the arguement I really need is take the mutation rate, estimated time frame and the amount of divergance.

quote:
The one discursive point you have raised is how Har1 has evolved so rapidly in humans. The obvious answer would be that the gene was subject to some selective pressure which favoured its divergence from the conserved sequence, either that or it was released from some strongly stabilising negative selective pressure.

You left out the part where you tell me how the mutation got in there without killing off the offspring.


This message is a reply to:
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jar
Member
Posts: 31764
From: Texas!!
Joined: 04-20-2004
Member Rating: 2.6


Message 8 of 157 (358195)
10-22-2006 8:33 PM
Reply to: Message 7 by eggasai
10-22-2006 8:28 PM


Re: Genes affecting brain development
You left out the part where you tell me how the mutation got in there without killing off the offspring.

One VERY common method is having multiple copies of a gene. Then one copy can be modified without losing any of the capabilities of the original.


Aslan is not a Tame Lion

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Wounded King
Member (Idle past 2433 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


Message 9 of 157 (358260)
10-23-2006 7:38 AM
Reply to: Message 7 by eggasai
10-22-2006 8:28 PM


Re: Genes affecting brain development
The observed mutation rate hovers around 2.5 x 10^-8 which comes to 173 germline mutations per diploid generation.

Except that you haven't provided any innformation for where those mutation rates come from. I have seen values around 2x10^-8 quoted as a mutation rate for single nucleotide polymorphism, but this would obviously not be a sufficient value to account for larger scale indels or chromosome rearrangements. On paper on this topic (Nachman and Crowell, 2000) gives the 2.5x10^-8 figure but cautions that the actual rate may be between 1.3 x 10-8 and 3.4 x 10-8. The largest indel they see is 4bp, can you see how 100Kb indels could throw off such calculations?

My point was that for large indels, and especially for large chromosomal rearrangments, large chunks of your divergence which needs accounted for will be achieved. you don't need 7 million years with 20 sites fixed per year if the fixation of one indel or chromosomal rearrangement will account for thousands to millions of bases itself.

Also, as I pointed out previously, the region in which the Har1 gene is located is more prone to mutation and consequently is highly likely to be above the average rate of mutation both in terms of specific types of nucleotide substitution, i.e. W->S, and of chromosomal recombination.

All the arguement I really need is take the mutation rate, estimated time frame and the amount of divergance.

The problem with such a simple formulation is that it is in fact overly simplistic.

You left out the part where you tell me how the mutation got in there without killing off the offspring.

I'm not sure why this is necessary in the absence of any evidence suggesting that such a mutation would be lethal. At best you have the indirect evidence that the 118bp non-coding region has been highly conserved in a number of vertebrate species, this is not the same as showing that any of the substitutions in the human gene are lethal in other animals. Indeed if you look at the supplementary data you will see that at least 3 of the mutations in the human are found in other species, and on assumes without lethal consequences and there are a further ten mutations seen in other species which are not present in the human gene. So at present there is no evidence to suggest that theHar1 region cannot accept a number of mutational changes without any lethal effect on offspring.

So why would we assume that any of these mutations would kill off the offspring in the absence of any evidence that this is the case?

TTFN,

WK


This message is a reply to:
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eggasai
Inactive Member


Message 10 of 157 (358609)
10-24-2006 6:29 PM
Reply to: Message 9 by Wounded King
10-23-2006 7:38 AM


Re: Genes affecting brain development
The fact is that the standard line has been that the DNA is 99% the same in chimpanzees and humans. When it was discovered over the last 5 or 6 years, that it's actually 95%, no one seemed supprised. Because of the indels the amount of known divergance went up by between 3-4%. I am actually talking to a geneticist who says that it's no big deal, I don't see how 100 million base pairs is no big deal.

There are a lot of variable in the mutation rate, that's not really the issue here. The observed mutation rate, measured in base pairs is not going to get you 300 germline mutations permenantly fixed for 7 million years. I'm trying to tell you that this simply does not happen.

quote:
The problem with such a simple formulation is that it is in fact overly simplistic.

It does not matter how you work the formula, the number of mutations required does not even come close to what actually happens. I cannot find an estimate of a mutation rate in any living system that nets that many germline mutations per diploid generation.

quote:
I'm not sure why this is necessary in the absence of any evidence suggesting that such a mutation would be lethal. At best you have the indirect evidence that the 118bp non-coding region has been highly conserved in a number of vertebrate species, this is not the same as showing that any of the substitutions in the human gene are lethal in other animals. Indeed if you look at the supplementary data you will see that at least 3 of the mutations in the human are found in other species, and on assumes without lethal consequences and there are a further ten mutations seen in other species which are not present in the human gene. So at present there is no evidence to suggest that theHar1 region cannot accept a number of mutational changes without any lethal effect on offspring.

We don't know, nor should we assume, that the 18 nucleotides in question are the result of mutations. Every time a nucleotide is substituted there is the danger of disease, defect or death. The nucleotide throws off the amino acid seqeunce, which throws off the protein seqeunce. That usually results in the reading frame being shut down, this one has 18 nucleotides that diverge between chimpanzees and humans. Mind you, this is in a crucial time of development, the cerbral cortex does not respond well to mutations in the regulatory genes. I see no reason that one cannot logically conclude that the differences are better accounted for by design rather then spontaneous mutations.

You say there are three mutations in other species. Are you describing a functional gene that remains the same in successive generations or an altered gene in a minority of the population?


This message is a reply to:
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RAZD
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Posts: 20326
From: the other end of the sidewalk
Joined: 03-14-2004
Member Rating: 3.6


Message 11 of 157 (358867)
10-25-2006 8:09 PM
Reply to: Message 5 by eggasai
10-19-2006 3:09 PM


Re: Chimpanzee genome
... was not 98%-99%, it was closer to 95%. ... Don't believe me? Type 'chimpanzee genome' into your google ...

The actual number is unimportant. The important thing is the relation of similarity between human and chimpanzee as compared to the similarity between human and gorilla or between chimpanzee and gorilla or between human and neanderthal and between chimpanzee and neanderthal - that show how closely related the different species are genetically.

What the number actually is becomes irrelevant compared to always ending up with humans closer to chimpanzees than gorillas, chimpanzees closer to humans than gorillas and neanderthals in between chimpanzees and humans in relatedness (but not linearly between).

Some of this has been discussed before on Comparisons of Neandertal mtDNA with modern humans and modern chimpanzees (although some of the graphics don't seem to load).

There have also been a number of threads on similarity:
We're Really Chimps???
"Homo troglodytes" Genome Project, DNA 96% {us}
From chimp to man: it's as easy as 1, 2, 3!
Chimpanzee-human genetic gap

And it seems all the studies still put us in the Chimpanzee neighborhood regardless of the actual number of genetic sequences that are identical.

The human brain is 3 times the size of Chimpanzees, I don't think I will get any arguements to the contrary. Recently they started studying the Human Accelerated Regions, there are 49.

I don't find this surprising at all, we've seen from the fossil evidence that brain size grew rapidly compared to other evolutionary changes in the species preceding Homo sapiens.

When the chimpanzee gene was compared to that of a chicken there were 2 substitutions. Chimps and chickens a believed to have a common ancestor 310 million years ago. The question arises how does such a highly conserved gene suddenly aquire 18 substitutions?
Francis Collins is one of the world's leading genetic researchers, I would love to hear him explain this.

Other than this being a standard argument from incredulity, there is no reason why substitutions in the areas related to significantly evolved features should not show a high degree of substitutions and other changes, especially compared to areas related to rather less significant changes.

I also suspect that there are a number of other brain related genes that show significant variation between chimpanzees and chickens, and that an unbiased debater would mention them as well.

But the real question you are asking in this oblique way, is how can some species have accelerated rates of evolution of some features while other related species do not eh?

The answer is selection pressure.

All species have roughly the same rates of mutations in similar areas, and these rates would be more similar the more related the species are yes?

Species living in the same environment would also have essentially the same survival selection pressure, and this pressure would also be more similar the more related the species are yes?

This would argue that the genetic relationship between humans and chimpanzees should be closer than chickens on pretty much every gene sequence, right? Except for one thing: sexual selection.

Sexual selection operates at every generation, not waiting for some disaster to change the environment to cause selection pressure on the individuals in a population. Normally this selection pressure operates to keep populations centered around a mean value - the most average individuals get the most breeding opportunities.

Runaway Sexual Selection though operates to one side of average and can drive a species to a heavy bias in one direction of evolution. Fisher described this process. Peacock tails are a normal example of this, but one of many in the bird family. Closely related species can be totally drab and inconsequential compared to the flamboyant species marked by Runaway Sexual Selection

This can be discussed separately (so as not to drag this topic off on a tangent) on Sexual Selection, Stasis, Runaway Selection, Dimorphism, & Human Evolution

Thus sexual selection can provide for very intense selection pressure on a species that far outranks normal selection pressure, and this higher selection pressure will result in a higher number of mutations being selected that offer the desired (literally) result.

Is this enough to conclude that sexual selection operated on the evolution of the human brain? No, but it is indicative, and the fact that we have other features that show similar effects of runaway sexual selection also lends credence to the concept:

  • extremely long head hair, much longer than any other primate on any part of its body,
  • extremely large male penis compared to any other ape species,
  • extremely large and constantly 'full' breasts compared to any other ape species,
  • extremely bare appearing skin, especially in females, compared to any other ape species, to the point where it requires behavioral adaptations for survival,
  • the aspect of 'neoteny' that is more fully developed in humans than any other ape species,
  • and finally, large brain size, bigger than any other ape species ...
Some of these may be inter-related (neoteny and 'bare'ness), but others aren't. Ones that can hinder survival in fully developed features are also indicative of "peacock" like runaway sexual selection, and the large head of humans fits this scenario as well -- any larger and it threatens the life of both the mother and the child.

We have multiple features showing evidence of extreme sexual selection, and ONE of them relates directly to the brain development in humans. There is also evidence that this sexual selection is still on-going: body shaving is becoming more common and extensive, for instance, and we need hardly mention porn to conjure up images of certain body types, sexual features, and sexual preferences.

The conclusion is that we are "human" because of sex.

The genetic data just confirms this eh?

Enjoy.


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This message is a reply to:
 Message 5 by eggasai, posted 10-19-2006 3:09 PM eggasai has responded

Replies to this message:
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eggasai
Inactive Member


Message 12 of 157 (358880)
10-25-2006 9:05 PM
Reply to: Message 11 by RAZD
10-25-2006 8:09 PM


Re: Chimpanzee genome
quote:
Lining up 3 billion bits of genetic code, the chimp genome team determined that 96 percent of the protein-coding genes in both chimps and humans were identical, while in some stretches of DNA where genes either regulate other genes or whose function is unknown, as much as 99 percent of the genetic material in both is identical, the scientists concluded.

I want to take another look at the original post but this one caught my attention. You are quoting from a news article based on a limited study. Why don't you check out the Initial Sequence fo the Chimpanzee Genome (Nature, 2005). They found that 29% of the protein coding genes were identical, not 96%. If you want to track it down it will give you something more current and definitive then the news article you are gleaning from.

I'll check back later and if you haven't responded I'll just edit and expand this post.


This message is a reply to:
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Replies to this message:
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Dr Adequate
Member
Posts: 16107
Joined: 07-20-2006
Member Rating: 8.3


Message 13 of 157 (358907)
10-25-2006 11:29 PM
Reply to: Message 1 by eggasai
08-18-2005 9:44 PM


You appear to be debating this twice, in parallel.

The other thread was actually started so you could provide the ID/creationist explanation of various features of the chimp and human genome. Perhaps you could give that a go, when you're not too busy?


This message is a reply to:
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Wounded King
Member (Idle past 2433 days)
Posts: 4149
From: Edinburgh, Scotland
Joined: 04-09-2003


Message 14 of 157 (358926)
10-26-2006 2:17 AM
Reply to: Message 10 by eggasai
10-24-2006 6:29 PM


Re: Genes affecting brain development
Every time a nucleotide is substituted there is the danger of disease, defect or death. The nucleotide throws off the amino acid seqeunce, which throws off the protein seqeunce.Every time a nucleotide is substituted there is the danger of disease, defect or death. The nucleotide throws off the amino acid seqeunce, which throws off the protein seqeunce.

Come on, the simplest knowledge of genetics shows this to be untrue. In almost a 3rd of cases a nucleotide substitution will have no effect on the amino acid due to third base wobble. Even in those cases where an amino acid substitution does take place there is still plenty of scope for a functionally equivalent substitution or at least one which does not severely impair the function of the protein. Of course this doesn't actually apply in the case of Har1Fwhich isn't even a protein coding gene. So while such highly conserved non-coding regions may show more conservation that coding regions there is still no evidence to support, and some to contradict, your claims as to changes in that region being necccessarily detrimental or lethal.

the cerbral cortex does not respond well to mutations in the regulatory genes.

Any actual evidence for this assertion? Just showing genes linked to geentic developmental abnormalities would be insufficient since that is a highly biased reporting set. Do you have any link to research showing, say, that induced point mutations in developmental neural genes usually lead to detrimental effects on the cerebral cortex?

I see no reason that one cannot logically conclude that the differences are better accounted for by design rather then spontaneous mutations.

Because we see spontaneous mutations occurring all the time. It is a question of an observed phenomenon with which we are well familiar and one based on a cloud of wishful thinking and religious dogma.

You say there are three mutations in other species. Are you describing a functional gene that remains the same in successive generations or an altered gene in a minority of the population?

What are you trying to say here? By 'altered gene' do you mean something which has been rendered non-functional? I am basing this on the supplemental data supplied in the paper, it is the data from which the comparison with the chick gene is derived. There are more than 3 mutations in other species, but there are 3 that are shared with the human mutations in the Har1 region sequence.

I can go back and check the papers exact methodology if you wish but I suspect that they got the data from the published genome sequences for the organisms they looked at, in which case the data is culled from more than one animal and is not likely to be a rare mutation. It certainly isn't likely to be a rare lethal mutation which is what you were suggesting any mutation in the gene would be.

TTFN,

WK


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mick
Member (Idle past 3324 days)
Posts: 913
Joined: 02-17-2005


Message 15 of 157 (358941)
10-26-2006 6:58 AM
Reply to: Message 12 by eggasai
10-25-2006 9:05 PM


Getting the numbers right
Eggasai writes:

I want to take another look at the original post but this one caught my attention. You are quoting from a news article based on a limited study. Why don't you check out the Initial Sequence fo the Chimpanzee Genome (Nature, 2005). They found that 29% of the protein coding genes were identical, not 96%. If you want to track it down it will give you something more current and definitive then the news article you are gleaning from.

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 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.

Just 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)

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%.

If (as seems likely) the probability that human and chimp orthologous proteins are identical is inversely proportional to protein length, this estimate will be a little high. Let us imagine, conservatively, that the average of 2 amino acids differing per protein was consistent across all proteins, not just the longest 71% of them. This would mean that the probability that two orthologous amino acids are identical is equal to (998/1000) or 99.8%.

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%!!!

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.

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.

Summary:

Probability that two orthologous amino acids are identical = 99.8%
Probability that two orthologous nucleotides are identical = 96%
Probability that two orthologous proteins are identical = 29%

Edited by mick, : added estimate of per-amino-acid divergence

Edited by mick, : added thread title and summary at the end

Edited by mick, : added mutation rate stuff


This message is a reply to:
 Message 12 by eggasai, posted 10-25-2006 9:05 PM eggasai has responded

Replies to this message:
 Message 17 by eggasai, posted 10-26-2006 8:40 PM mick has responded
 Message 19 by eggasai, posted 10-27-2006 1:31 AM mick has responded
 Message 61 by eggasai, posted 10-29-2006 11:41 PM mick has responded

  
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