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Author Topic:   Genetic Equidistance: A Puzzle in Biology?
Livingstone Morford
Junior Member (Idle past 2846 days)
Posts: 28
From: New Mexico
Joined: 12-13-2010


Message 1 of 89 (596754)
12-16-2010 6:46 PM


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? Indeed, if the epigenetic complexity of an organism does impose a such restraint, then the genetic equidistance result would still be observed, regardless of the time that has lapsed since divergence.

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.

Edited by Adminnemooseus, : Add a blank line - Because I had nothing easy better to do.


Replies to this message:
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Admin
Director
Posts: 12578
From: EvC Forum
Joined: 06-14-2002
Member Rating: 4.8


Message 2 of 89 (596766)
12-16-2010 7:49 PM
Reply to: Message 1 by Livingstone Morford
12-16-2010 6:46 PM


Google returns nothing for "epigenetic equidistance." You'll have to explain a bit more.


--Percy
EvC Forum Director

This message is a reply to:
 Message 1 by Livingstone Morford, posted 12-16-2010 6:46 PM Livingstone Morford has responded

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Livingstone Morford
Junior Member (Idle past 2846 days)
Posts: 28
From: New Mexico
Joined: 12-13-2010


Message 3 of 89 (596772)
12-16-2010 8:07 PM
Reply to: Message 2 by Admin
12-16-2010 7:49 PM


There is no such thing as "epigenetic equidistance."

Google "genetic equidistance" and you'll get the necessary information.

To quote Wikipedia,
"The genetic equidistance phenomenon was first noted in 1963 by E. Margoliash, who wrote: "It appears that the number of residue differences between cytochrome C of any two species is mostly conditioned by the time elapsed since the lines of evolution leading to these two species originally diverged. If this is correct, the cytochrome c of all mammals should be equally different from the cytochrome c of all birds. Since fish diverges from the main stem of vertebrate evolution earlier than either birds or mammals, the cytochrome c of both mammals and birds should be equally different from the cytochrome c of fish. Similarly, all vertebrate cytochrome c should be equally different from the yeast protein." 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%. Together with the work of Emile Zuckerkandl and Linus Pauling, the genetic equidistance result directly led to the formal postulation of the molecular clock hypothesis in the early 1960s. Genetic equidistance has often been used to infer equal time of separation of different sister species from an outgroup."

Edited by Adminnemooseus, : Add the quote box for the quoted material, etc.


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Adminnemooseus
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Posts: 3879
Joined: 09-26-2002


Message 4 of 89 (596798)
12-16-2010 10:53 PM


Thread Copied from Proposed New Topics Forum
Thread copied here from the Genetic Equidistance: A Puzzle in Biology? thread in the Proposed New Topics forum.
    
crashfrog
Inactive Member


(1)
Message 5 of 89 (596799)
12-16-2010 11:02 PM
Reply to: Message 1 by Livingstone Morford
12-16-2010 6:46 PM


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?

I've mostly covered this in the other thread, but the quick answer is that we know that genetic distance is the result of time and not a pattern of increasing constraint on organisms, because we measure genetic distance based on genes that are subject to far greater restriction as a result of function than they could possibly be subject to as a result of increasing complexity - cytochrome c, ribosomal subunit 16S, and so on. These proteins have identical functions regardless of cell type, cell diversity, or organism complexity. Every cell in your body, for instance, needs to express proteins.

Also, a pattern of increased restraint on tolerance of mutations wouldn't produce genetic equidistance, it would produce a pattern of decreasing distance as a result of complexity. Under your model, humans would exhibit less genetic distance from yeasts than trout do, but what we observe is that both humans and trout exhibit equidistance from yeasts, reflecting the evolutionary time since the line that resulted in modern humans diverged from the line that resulted in modern trout.

Edited by crashfrog, : Whew, run-on!

Edited by Adminnemooseus, : Added link to most recent relevant message in "other thread".


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molbiogirl
Member (Idle past 714 days)
Posts: 1909
From: MO
Joined: 06-06-2007


Message 6 of 89 (596859)
12-17-2010 11:54 AM


LM writes:

Since flowers are less epigenetically complex than mammals, if my assertion is correct, there would be more genetic diversity among flowering plants than among mammals.

Can I assume that by "genetic diversity" you are referring to the coding regions of DNA?

If so, then you run into the problem that Taq raised in the last thread.

To wit:

Taq writes:

However, coding DNA makes up a tiny portion of the whole genome, somewhere around 3%. In this model, the other 97% of the genome is diverging through drift so the predominant force of genetic change is still drift.

And:

Selection is hard to put into the calculations so population geneticists try to use selectively neutral DNA seqeunces that can be readily identified (especially for genomic position to rule out duplication events). One good source for these sequences is pseudogenes, which is exactly what this group used:

http://www.ncbi.nlm.nih.gov/pubmed/8364591


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Taq
Member
Posts: 7672
Joined: 03-06-2009
Member Rating: 3.2


Message 7 of 89 (596873)
12-17-2010 1:25 PM


Mr. Morford,

I was trying to think of a way to test your ideas. I was thinking of comparing sponges, mammals, and fungi to see if they were genetically equidistant. Sponges do have a limited set of genes that control development, but they are primitive compared to the gene regulation and development pathways found in mammals. Does this sound like a good test?

Edited by Taq, : No reason given.


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molbiogirl
Member (Idle past 714 days)
Posts: 1909
From: MO
Joined: 06-06-2007


Message 8 of 89 (596876)
12-17-2010 2:03 PM


Just FYI for everyone
This is where LM seems to be getting his ideas:

http://thegoldengnomon.blogspot.com/

In particular, this page (see comments):

http://thegoldengnomon.blogspot.com/...r-first-axiom-of.html

And this paper:

http://precedings.nature.com/documents/1751/version/2


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Livingstone Morford
Junior Member (Idle past 2846 days)
Posts: 28
From: New Mexico
Joined: 12-13-2010


Message 9 of 89 (596894)
12-17-2010 6:22 PM
Reply to: Message 5 by crashfrog
12-16-2010 11:02 PM


“Well, no, we're not. The function of proteins like cytochrome c or ribosomal subunit 16S aren't related to cell type, because the function is so basic every kind of cell in every kind of organism needs to perform it. All of your cells, regardless of type, are engaging in protein synthesis and electron transport activity, or else they're dead.”

I’m not sure you get the gist of my argument. For example, an ontogenic amino acid substitution in a human protein must be compatible with every one of the different cell types found in the human organism (every cell, that is, that contains the protein), while an amino acid substitution in say, a yeast protein must be compatible with only one cell type.
An analogy may (in a theoretical sense) be useful here. Say you have protein A. And you have cell type X, Y, and Z. Any substitution mutation in protein A must be compatible with all three cell types. Meanwhile, if you only have cell type X, then protein A needs only to compatible with X (analogy a la Dr. Shi Huang).
In light of this elaboration, I don’t think your above argument is pertinent.

“Cell type and cell diversity is going to have no effect whatsoever on these highly conserved proteins, and that's how we know that accumulated differences between homologous genes in different organisms really do reflect evolutionary time.”

If the number of cell types in an organism does not impose a restraint on how many mutations are tolerated, then what is your explanation for the observation that conserved sequences in simple organisms are always conserved in complex organisms, but the reverse is not necessarily true? Also, why is it that simple organisms that have been diverging for the same amount of time as complex organisms generally display more genetic diversity?
The proposition that the number of tissues in an organism does not impose a restraint on the amount of mutations tolerated is in conflict with Xun and Zhixi (2007), where we see:
“To maintain normal physiological functions, different tissues may have different developmental constraints on expressed genes. Consequently, the evolutionary tolerance for genomic evolution varies among tissues.”

And,
“We conclude that tissue factors should be considered as an important component in shaping the pattern of genomic evolution and correlations.”

“Well, but it's not. We know it's not because, again, genetic distance is being measured only on genes that have nothing to do with cell type, cell diversity, or epigenetic complexity.”

See my elaboration above. Also note that the genetic equidistance phenomenon is manifested in many proteins, not just proteins which have high levels of functional complexity. I’m starting to get the idea that you really don’t quite understand my assertion – and that’s probably my fault for not being clear enough.
“Regardless of how complex an organism you are, your mitochondria engage in electron transport and your cells express proteins.”

True, but you are not attacking my argument. The more complex an organism is, then the less substitutions the cytochrome-c of that organism can tolerate, since any given substitution must be compatible with all the different tissues.

“By only measuring the genetic distance on proteins that have identical function between the compared species regardless of complexity, like cytochrome c and ribosomal subunit 16S.”

See my elaboration.

References:

Xun Gu, Zhixi Su. Tissue-driven hypothesis of genomic evolution and sequence-expression correlations. PNAS, 104 (8): 2779-2784 (2007).


Biology rocks!
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Livingstone Morford
Junior Member (Idle past 2846 days)
Posts: 28
From: New Mexico
Joined: 12-13-2010


Message 10 of 89 (596895)
12-17-2010 6:23 PM
Reply to: Message 5 by crashfrog
12-16-2010 11:02 PM


“…the quick answer is that we know that genetic distance is the result of time and not a pattern of increasing constraint on organisms, because we measure genetic distance based on genes that are subject to far greater restriction as a result of function than they could possibly be subject to as a result of increasing complexity - cytochrome c, ribosomal subunit 16S, and so on.”

Firstly, as I pointed out earlier, the genetic equidistance phenomenon is manifested in many proteins, and not only proteins that have high levels of functional complexity. Secondly, with regards to your statement that genetic distance is measured in genes that “are subject to far greater restriction as a result of function than they could possibly be subject to as a result of increasing complexity,” let us realize that neutral amino acid substitutions are allowed in cytochrome-c. However, what I am arguing is that a neutral amino acid subsitution in yeast cytochrome-c is not necessarily neutral in a considerably more complex organism because that substitution must be compatible with all the different tissue types found in that organism.

“Under your model, humans would exhibit less genetic distance from yeasts than trout do, but what we observe is that both humans and trout exhibit equidistance from yeasts…”

Genetic distance between a complex clade and a simpler outgroup is equivalent to the genetic diversity of the simpler outgroup. Therefore, the distance between trout and yeast and between humans and yeast is determined by the genetic diversity of yeast and not that of the trout or human (a la Dr. Shi Huang). For more background information, you might want to read Dr. Huang’s paper on the maximum genetic diversity hypothesis.


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Livingstone Morford
Junior Member (Idle past 2846 days)
Posts: 28
From: New Mexico
Joined: 12-13-2010


Message 11 of 89 (596896)
12-17-2010 6:24 PM
Reply to: Message 5 by crashfrog
12-16-2010 11:02 PM


“…and the fact that this pattern is observed in highly conserved genes supports the concept of molecular clocks…”

Your position cannot be reconciled with particular observations from protein sequences, particularly one observation. A ClustalW alignment of the cytochrome-c sequences of homo sapiens, the alligator, and the frog, reveal that the frog and the alligator are equidistant to humans by 13 residues each. Of these 13 different residues, 7 of them are located in the same position in the alligator and the frog.
To calculate how many of these positions should be shared, based on chance and probability, the following may be done:

The chance for a position to be different between human and frog is 13/105.
The chance for a position to be different between human and alligator is 13/105.
The number of positions that would overlap based on chance: 13/105 x 13/105 x 105 = 1.6
In a word, the molecular clock would predict that only 1.6 differing positions (differing from the human cytochrome-c) would be shared by the alligator and the frog. However, this is not the case, as 7 differing positions are shared by the alligator and the frog. This is explained by the thesis I am arguing for, but how does the molecular clock explain this?

For a more detailed summary of this feature, see Huang, Shi. The Overlap Feature of the Genetic Equidistance Result—A Fundamental Biological Phenomenon Overlooked for Nearly Half of a Century. MIT Press Journals – Biological Theory, 5(1): 40 – 52 (2010).


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Livingstone Morford
Junior Member (Idle past 2846 days)
Posts: 28
From: New Mexico
Joined: 12-13-2010


Message 12 of 89 (596897)
12-17-2010 6:25 PM
Reply to: Message 6 by molbiogirl
12-17-2010 11:54 AM


“Can I assume that by "genetic diversity" you are referring to the coding regions of DNA?”

Yes.

“If so, then you run into the problem that Taq raised in the last thread.”

Respectfully, the problem that Taq raised is irrelevant. The predominant force of genetic change is genetic drift; however, the question is what causes the phenomenon of genetic equidistance. At the fundamental level, it is the result of genetic drift. But is the assumption that genetic distance is determined by the time lapsed since divergence correct? I think not.

On a slight tangent, I did a PubMed search of “genetic equidistance in pseudogenes” and found no results. Does anyone know if the phenomenon of genetic equidistance is prevalent in pseudogenes?


Biology rocks!
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Livingstone Morford
Junior Member (Idle past 2846 days)
Posts: 28
From: New Mexico
Joined: 12-13-2010


Message 13 of 89 (596898)
12-17-2010 6:26 PM
Reply to: Message 7 by Taq
12-17-2010 1:25 PM


“I was trying to think of a way to test your ideas.”

They’re not mine.

“I was thinking of comparing sponges, mammals, and fungi to see if they were genetically equidistant.”

Let me understand this. You’re going to be aligning the protein sequences of what clade to what simpler outgroup? Of these three taxonomic groups you suggest, fungi would be the simplest. Hence, the more complex clade consisting of mammals and sponges would be aligned against the simpler outgroup. Sponges and mammals will be equidistant to fungi.


Biology rocks!
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crashfrog
Inactive Member


Message 14 of 89 (596903)
12-17-2010 7:10 PM
Reply to: Message 9 by Livingstone Morford
12-17-2010 6:22 PM


I’m not sure you get the gist of my argument.

I'm not sure you know any biochemistry.

For example, an ontogenic amino acid substitution in a human protein must be compatible with every one of the different cell types found in the human organism

This makes no sense. Every single amino acid can be found in every single human cell, so there's no such thing as a substitution that would be "incompatible" with the cell. Now it is indeed possible for the function of a protein to be eliminated by even a single substitution - say, a substitution that disrupts a critical hydrophobic region and alters protein folding and disrupting an active site, or eliminates or moves a critical catalytic residue. But that's going to have nothing to do with cell diversity.

Say you have protein A. And you have cell type X, Y, and Z. Any substitution mutation in protein A must be compatible with all three cell types.

No, this makes no sense. Protein A may not be expressed in X, Y, or Z, or it may be subject to alternate splicing such that the mutation in the gene for A is in a region that is not expressed in one of those cells. And really, there's no such thing as "cell type", there's just different patterns of gene expression and regulation in different cells. The fact that two different cells may have different patterns of gene expression really doesn't say anything at all about which mutations will prove fatal in which cells.

In light of this elaboration, I don’t think your above argument is pertinent.

No, it remains pertinent. Regardless of cell type, all cells in your body are engaged in electron transport chain activity - you breathe air, I assume? - and protein translation.

If the number of cell types in an organism does not impose a restraint on how many mutations are tolerated, then what is your explanation for the observation that conserved sequences in simple organisms are always conserved in complex organisms, but the reverse is not necessarily true?

What is your source for this observation? And I don't see the relevance - your model doesn't explain it either, and it's a perfectly explainable observation under the scientific consensus of evolution.

Also note that the genetic equidistance phenomenon is manifested in many proteins, not just proteins which have high levels of functional complexity.

I never said that it was not.

The more complex an organism is, then the less substitutions the cytochrome-c of that organism can tolerate, since any given substitution must be compatible with all the different tissues.

The functional residues of cytochrome C are very highly conserved; almost no organism can tolerate any mutation of these residues. We're talking about residues that are not related to catalytic function.

We're talking about silent mutations, in other words, and since these mutations are silent cell type and tolerance is irrelevant - a cell can tolerate any number of silent mutations because they don't change protein function.


This message is a reply to:
 Message 9 by Livingstone Morford, posted 12-17-2010 6:22 PM Livingstone Morford has acknowledged this reply

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crashfrog
Inactive Member


Message 15 of 89 (596907)
12-17-2010 7:43 PM
Reply to: Message 10 by Livingstone Morford
12-17-2010 6:23 PM


Firstly, as I pointed out earlier, the genetic equidistance phenomenon is manifested in many proteins, and not only proteins that have high levels of functional complexity.

I never said that they were. But, clearly, proteins subject to less conservation are subject to more selection, and selection alters genes in different ways that genetic drift. So, selection-heavy proteins are less likely to exhibit genetic equidistance. This pattern is observed.

However, what I am arguing is that a neutral amino acid subsitution in yeast cytochrome-c is not necessarily neutral in a considerably more complex organism because that substitution must be compatible with all the different tissue types found in that organism.

I know, and this is utterly wrong. Cytochrome c isn't in the environment of the cell, it's buried deep in the intermembranous space of the mitochondria, and from that perspective all cells are basically the same. There's nothing in the pattern of protein expression and regulation - which is what actually makes cells different from each other - that's going to "check" mutations to cytochrome c. The only thing that's going to "check" a mutation in cytC is whether or not it still has electron transport activity. Oxidative phosphorylation is essentially the same in all eukaryotic cells which is why it's such a canonical metabolic pathway.

Therefore, the distance between trout and yeast and between humans and yeast is determined by the genetic diversity of yeast and not that of the trout or human (a la Dr. Shi Huang).

No, it's not. If Shi Huang says this, Shi is wrong. But I suspect you've simply got your wires crossed.


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