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Author Topic:   Genetic Equidistance: A Puzzle in Biology?
Taq
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Posts: 8207
Joined: 03-06-2009
Member Rating: 3.9


(1)
Message 61 of 89 (597552)
12-22-2010 11:58 AM
Reply to: Message 59 by Dr Jack
12-22-2010 5:09 AM


Re: Cytochrome C is not encoded by mtDNA
Cytochrome c is encoded by nuclear DNA* and imported into the mitochondria, rather than encoded by the mitochondria DNA itself. While what you describe here would be true for the four transport proteins themselves, it is not true for cytochrome c.

It appears I need to study up on the mit genome. Thanks for the correction.


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Dr Jack
Member (Idle past 444 days)
Posts: 3507
From: Leicester, England
Joined: 07-14-2003


Message 62 of 89 (597555)
12-22-2010 12:16 PM
Reply to: Message 60 by Taq
12-22-2010 11:57 AM


Re: The Crash Promise
As you note, apoptosis is not merely part of cell dysfunction, it's an absolutely vital part of the development of multi-cellular organisms. Key developmental mechanisms such as those producing the separation of the fingers, and the correct routing of nerve fibres from the eyes to the visual regions of the brain rely on apoptosis to function correctly. Not all of this developmental apoptosis occur via cytochrome c involving pathways, but some of it certainly does.

Whether this provides any support at all for Mr. Morford's wider principles is another matter but let us at least criticise his notions on the basis of factually correct science, hey?


This message is a reply to:
 Message 60 by Taq, posted 12-22-2010 11:57 AM Taq has responded

Replies to this message:
 Message 63 by Taq, posted 12-22-2010 12:43 PM Dr Jack has responded

  
Taq
Member
Posts: 8207
Joined: 03-06-2009
Member Rating: 3.9


(1)
Message 63 of 89 (597559)
12-22-2010 12:43 PM
Reply to: Message 62 by Dr Jack
12-22-2010 12:16 PM


Re: The Crash Promise
Whether this provides any support at all for Mr. Morford's wider principles is another matter but let us at least criticise his notions on the basis of factually correct science, hey?

I agree. However, every cell with mitochondria expresses cytc. Therefore, cytc can not be used to differentiate tissues or initiate specific developmental apoptotic pathways. Is it possible that cytc is involved further down in the pathway beyond initiation? Very possible. However, it is the initiation of the pathway during development that is important.

What would be interesting is to see how specific the binding is between cytc and and the triggers of the apoptotic pathway. Is it possible to switch cytc or the apoptotic proteins that bind to cytc between distantly related organisms? That would be interesting.


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 Message 62 by Dr Jack, posted 12-22-2010 12:16 PM Dr Jack has responded

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Dr Jack
Member (Idle past 444 days)
Posts: 3507
From: Leicester, England
Joined: 07-14-2003


Message 64 of 89 (597567)
12-22-2010 1:02 PM
Reply to: Message 63 by Taq
12-22-2010 12:43 PM


Re: The Crash Promise
What would be interesting is to see how specific the binding is between cytc and and the triggers of the apoptotic pathway. Is it possible to switch cytc or the apoptotic proteins that bind to cytc between distantly related organisms? That would be interesting.

That's an interesting question, so I decided to look a little deeper. It seems that cytochrome c's involvement is limited to particular groups of animals (I'm not sure how large a group but certainly including mammals). In nematodes (or C. elegans, at least) rather than pro-apoptotic proteins interacting with mitochondria to release Cytochrome c which then joins with other proteins to form the apoptosome, their equivalent pro-apoptotic proteins directly complex with other proteins to form the apoptosome. So the whole cytochrome c requiring apoptotic step is absent.


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Livingstone Morford
Junior Member (Idle past 3113 days)
Posts: 28
From: New Mexico
Joined: 12-13-2010


(1)
Message 65 of 89 (597640)
12-22-2010 8:50 PM


A Quick Note
No I have not suddenly vanished and decided to never return. Rather, the last few days have been quite busy for me, and now have the time to devote my energies on responding to my opponents. However, given the large amount of posts I need to respond to, this will take a while.
Just saying...

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Panda
Member (Idle past 2052 days)
Posts: 2688
From: UK
Joined: 10-04-2010


(1)
Message 66 of 89 (597642)
12-22-2010 9:02 PM
Reply to: Message 65 by Livingstone Morford
12-22-2010 8:50 PM


Re: A Quick Note
LM writes:

Rather, the last few days have been quite busy for me, and now have the time to devote my energies on responding to my opponents.


Good quality posts are always more appreciated than rushed replies.
This is not meant to be a race.

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Livingstone Morford
Junior Member (Idle past 3113 days)
Posts: 28
From: New Mexico
Joined: 12-13-2010


Message 67 of 89 (598241)
12-29-2010 6:24 PM
Reply to: Message 38 by crashfrog
12-19-2010 6:33 PM


Re: The Crash Promise
There certainly does seem to be a lot of attempts to refute the model I am advocating. So all of you can imagine just how much time is required to respond to all of your posts. Regardless,
quote:

Yes, there are. The cell is such a complex place that you really can't say, except in the specific, whether or not mutations are related to cell type diversity.

I take it that “the specific” is a reference to the examples I cited above (see the citations I provided)? While we cannot boldly assert as fact whether or not mutations are related to tissue diversity, we can make this assertion with a fair degree of confidence, given the evidence for it.

Since it seems like you are building a case around cytochrome-c, and since I believe you are suggesting that some proteins are under tissue constraints while others, such as cytochrome-c, are not, then I would be interested to hear what your thoughts are on the evidence that cytochrome-c is also under tissue constraints. Before I begin, it is suggested that one reads up on the overlap feature of the genetic equidistance result, or else the remainder of this post may appear to be gibberish.
Namely, the overlap feature of the genetic equidistance result [see, for example: Huang, 2010] (note: the paper I am citing is in fact peer-reviewed).
To name an example of this feature (and I might advise that anyone with a rudimentary knowledge of protein alignments can confirm what I am saying here): human cytochrome-c differs from the fruit fly cytochrome-c in 22 positions; and human cytochrome-c differs from the yeast cytochrome-c in 36 positions. Of the 22 variant residues between humans and fruit flies, 17 of these residues are also different between human and yeast cytochrome-c.
How many overlapping residues is predicted in your model?
Huang (2010) states that,
The chance for a position to be different between human and yeast is 36/102; the chance for a position to be different between human and drosophila is 22/102; the number of overlap positions should be: 36/102 x 22/102 x 102 = 7.76– based on probability. However, the actual number of overlapping residues is 17. This observation is completely consistent with the model I am advncing, but it is not at all compatible with the model you are advocating. Note that the overlap feature is observed in not just cytochrome-c, but in many proteins. Thus, the overlap feature indicates that cytochrome-c is under tissue constraints, as are all proteins.
Any attempt to refute this feature must take into account the following:
1) The number of overlap positions follows probability when organisms of similar complexity are compared, such as different yeast strains. However, when organisms of different complexity are compared, the number of overlap positions violate probability theory.
2) Remarkably, in tissue-specific proteins that are not subject to as stringent constraints as other proteins, the overlap feature follows probability. An example may be cited here. When the alpha-crystallin of the chicken and the elephant is compared against the alpha-crystallin of humans, we find the elephant alpha-crystallin differs from human alpha-crystallin by 8 residues; of these 8 variant positions, 6 (out of 29) of them are also variant in the chicken alpha-crystallin: i.e. there are 6 overlap positions. A cursory alignment among seven different organisms will reveal that approximately 50 residues are conserved and therefore not subject to as many mutations. So, even though the alpha-crystallin protein is 173 aa in length (in humans), we substract 50 residues. Thus, the most realistic calculation of how many overlap positions we would expect in your model is as follows:
The chance for a position to be different between human and chicken is 29/123; the chance for a position to be different between human and elephant is 8/123; the number of overlap positions should be: 29/123 x 8/123 x 123 = 1.89, falling short of the 6 actual overlap positions.
Now, if we align the alpha-crystallin of the chicken and the blind mole rat against the human alpha-crystallin, we end up with different results.
The chicken alpha-crystallin differs from the human protein by 29 residues; the blind mole rat protein differs from the human protein by 17 residues. Of these 17 variant residues, 5 are overlapping positions. Now it’s time to plug in our calculations. The chance for a position to be different between human and chicken is 29/123; the chance for a position to be different between human and the blind mole rat is 17/123; the number of overlap positions should be: 29/123 x 17/123 x 123 = 4.0, a number very close to the actual number of overlap positions. These results are very remarkable because the alpha-crystallin of the blind mole rat are not under tissue constraints (the tissue where alpha-crystallin is located is nonfunctional in the blind mole rat, hence the lack of tissue constraints).
So we see that for proteins that are not under tissue constraints, the number of overlap positions follows what we would expect based on probability. It is because of this that I must conclude that cytochrome-c is under tissue constraints. I certainly am willing to be corrected as to why my assertion is not valid, but the above evidence will have to be refuted first.

I realize that PaulK has attempted to refute the overlap feature, but his refutation has failed to take into account the above two points I delineated above, and I hope to demonstrate the other errors in Paul's rebuttal (emphasis on the word "hope").

P.S. Having done this, I will labor on more replies to my other opponents. Stay tuned.

Edited by Livingstone Morford, : No reason given.


Biology rocks!

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Replies to this message:
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molbiogirl
Member (Idle past 981 days)
Posts: 1909
From: MO
Joined: 06-06-2007


Message 68 of 89 (598348)
12-30-2010 1:00 PM
Reply to: Message 67 by Livingstone Morford
12-29-2010 6:24 PM


Huang's paper is not peer reviewed
Namely, the overlap feature of the genetic equidistance result [see, for example: Huang, 2010] (note: the paper I am citing is in fact peer-reviewed).

No. It isn't. It was published in a book. While a paper that is published in a book may get editorial approval from the publisher, it is not peer reviewed.

Peer-reviewed literature (sometimes called refereed publications) are scholarly works that typically represent the latest original research in the field, research that has been generally accepted by academic and professional peers for dissemination and discussion.

Peer-reviewed books are generally published by university presses and scholarly publishing houses like University of Washington Press or Inter-Research. One way of distinguishing these books from those published by more commercial houses is to search Publishers' Catalogues online. Frequently, major publishing houses will provide separate names for their scholarly publishing operations and will provide a statement of their publishing philosophy somewhere on their Web site.

http://www.lib.washington.edu/...20sciences/peer-review.html

Cancer epigenetics is a commercial publication.

http://www.crcpress.com/product/isbn/1420045792

Shi tried to get published in the peer reviewed literature (JEZ), but couldn't. Remember?

Dear Dr. Huang,

I have now had a chance to read your manuscript and I regret that I am not recommending publication in JEZ-B. While the ideas presented are very intriguing, several key elements lack rigorous definitions and, as written, are inconsistent with observations from across the tree of life. For example, the view of phylogenetic diversity is more consistent with the Scala Natura than current understanding of the tree of life and the nature of biological diversity on Earth. Similarly, the treatment of the term complexity is simplistic at times. For example, limb number is certainly one measure of complexity (e.g. snakes vs. other reptiles) but, if "complex organisms are here defined as those that have complex epigenetic programs" then organisms like ciliates, which rely on epigenetic mechanisms to scan the last generation's somatic genome in forming the next generation's somatic genome, may also be worth considering. As written, the manuscript reads as if humans are the pinnacle of both the tree of life and complexity. Further, the treatment of genetic distance is also simplistic at times, particularly given what we know about patterns and processes driving molecular evolution across genomes.

I do hope that this quick turn around enables you to find a more appropriate journal for your interested manuscript without any unnecessary delay.

Sincerely,

Laura Katz

Edited by molbiogirl, : No reason given.


This message is a reply to:
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Replies to this message:
 Message 71 by Livingstone Morford, posted 12-30-2010 7:51 PM molbiogirl has responded

  
PaulK
Member
Posts: 15639
Joined: 01-10-2003
Member Rating: 2.8


Message 69 of 89 (598372)
12-30-2010 3:07 PM
Reply to: Message 67 by Livingstone Morford
12-29-2010 6:24 PM


Re: The Crash Promise
quote:

I realize that PaulK has attempted to refute the overlap feature, but his refutation has failed to take into account the above two points I delineated above, and I hope to demonstrate the other errors in Paul's rebuttal (emphasis on the word "hope").

I think that hope is in vain. Surely you accept the basic point that if a mutation in the human lineage produces a change at a position which is unchanged in the other two lineages (unchanged since the mutual common ancestor of all 3 lineages, that is) then there will automatically be an overlap. How can it possibly be otherwise ?


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PaulK
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Posts: 15639
Joined: 01-10-2003
Member Rating: 2.8


Message 70 of 89 (598380)
12-30-2010 3:24 PM
Reply to: Message 67 by Livingstone Morford
12-29-2010 6:24 PM


Re: The Crash Promise
To consider your two points:

1) You claim that Shi Huang's calculations work for different yeast strains. But since that is all that you say, there is nothing more to deal with. Personally I doubt that that is entirely true- I suspect "cherry picking" of data.

2) You claim that the results match Shi Huang's calculations when a protein is not under selective constraint, citing the blind mole rat. However, if the blind mole-rat alpha-crystallin is not under selective constraint it will change much faster by genetic drift, and thus the mutations - which are what we should be looking at - will be far more frequent in the blind mole rat lineage. As I have stated the overlap is dominated by mutations in the human lineage, so the overlap should be well under half the number of differences with the blind mole rat, consistent with the results.
Interestingly this offers a chance for a real test. If we use the blind mole rat instead of the human as our "middle" group we should find a much greater overlap (i.e. positions where the blind mole rat is different from both human and chicken). Want to take that test ?


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Livingstone Morford
Junior Member (Idle past 3113 days)
Posts: 28
From: New Mexico
Joined: 12-13-2010


Message 71 of 89 (598421)
12-30-2010 7:51 PM
Reply to: Message 68 by molbiogirl
12-30-2010 1:00 PM


Re: Huang's paper is not peer reviewed
While I am attempting to gather the time to muster a more adequate response to all of you (patience is a virtue, so I've heard), I will make a quick note to molbiogirl's post:
You will please note that I was not referring to Dr. Huang's MGD paper, but rather his paper on the overlap feature of the genetic equidistance result -- and that paper was peer-reviewed and is published in the MIT Press Journal of Biological Theory. Does that satisfy you?


Biology rocks!

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 Message 68 by molbiogirl, posted 12-30-2010 1:00 PM molbiogirl has responded

Replies to this message:
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molbiogirl
Member (Idle past 981 days)
Posts: 1909
From: MO
Joined: 06-06-2007


Message 72 of 89 (598484)
12-31-2010 1:44 PM
Reply to: Message 71 by Livingstone Morford
12-30-2010 7:51 PM


Re: Huang's paper is not peer reviewed
In the future, please provide links for your cites.

For everyone else:

Huang's overlap paper.

http://www.mitpressjournals.org/doi/abs/10.1162/BIOT_a_00021


This message is a reply to:
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Livingstone Morford
Junior Member (Idle past 3113 days)
Posts: 28
From: New Mexico
Joined: 12-13-2010


Message 73 of 89 (598502)
12-31-2010 5:08 PM
Reply to: Message 72 by molbiogirl
12-31-2010 1:44 PM


Re: Huang's paper is not peer reviewed
Oops, I just realized that I did not add the full citation at the end of my post. My bad.

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derwood
Member (Idle past 215 days)
Posts: 1457
Joined: 12-27-2001


Message 74 of 89 (599140)
01-05-2011 8:22 AM
Reply to: Message 11 by Livingstone Morford
12-17-2010 6:24 PM


Just a few thoughts on this.

It appears that Huang is one of those few scientific folks who simply cannot accept the notion that humans are closely related to chimps and so goes to great lengths to try to justify his prejudices.

One should check out his amazon.com review of Coyne's book - he comes across more as an anti-evolution zealot than a legitimate scientist. His frequent references to Lovtrup and the like indicate a rather skewed view of what constitutes valid science.
He is a classic ReMine-style huckster - from one of his comments on Amazon:

"If this result supports rather than contradicts NeoDarwinism, Coyne's book or any Darwinist's would be all over it. Instead, the Darwinists have managed to keep this result unknown to 100% of lay people and 99% of all biologists for 46 years. I have to re-discover it independently a few years ago."

He is talking about genetic equidistance. Something one can read about in any molecular biology textbook. And something one does not actually see when one looks at large datasets.

I liked this response to Huang as well:

"To those who are wondering, Nature describes the forum in which Huang deposited his work thusly: "Documents on Nature Precedings are not peer-reviewed and, as such, should not be considered 'published' works."

IOW, Huang, on these issues anyway, has about as much credibility as Rush Limbaugh has on family values.

Edited by derwood, : added link


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derwood
Member (Idle past 215 days)
Posts: 1457
Joined: 12-27-2001


Message 75 of 89 (599146)
01-05-2011 8:41 AM
Reply to: Message 1 by Livingstone Morford
12-16-2010 6:46 PM


quote:
Here I wish to discuss my thesis that the phenomenon of genetic equidistance presents a problem in biology: how do we know if this phenomenon is the result of the amount of time that has lapsed since any two or more organisms have diverged, or is it largely the result of the epigenetic complexity of organisms imposing restraints on the amount of mutations those organisms tolerate?

As it appears that Huang has read the Wiki entry on the molecular clock (as he uses the same ref and quote found there in one of his Amazon.com comments), I should like ot also quote the Wiki entry on Molecular Clocks in regards to equidistance:

For example, the difference between the cytochrome C of a carp and a frog, turtle, chicken, rabbit, and horse is a very constant 13% to 14%. Similarly, the difference between the cytochrome C of a bacterium and yeast, wheat, moth, tuna, pigeon, and horse ranges from 64% to 69%.

1% off here, 5% off there, but 'equidistance' nonetheless.

As has been, I believe, pointed out, the 'epi' part of epigenetics must work on the 'genetics' part. Methylation, etc. does not constrain the underlying sequence; quite the opposite.
Epigenetics is the new buzzword, especially among anti-evolutionist propagandists. But buzzwords co-opted by such folk often have a way of biting them in the arse, once their intellectually capable targets actually look into the issues themselves and discover that their handlers have been overstating their case, such as what happened re: junkDNA.

quote:

On a slight tangent, if this was the case, then functionally redundant protein sequences cannot always give us accurate conclusions with regards to phylogenetic relationships.

Which is probably why DNA sequence data is preferred in such analyses.


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