Krebs Cycle

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Krebs Cycle

Postby Roger Stanyard » Tue Mar 06, 2007 9:47 am

Krebs Cycle

The Intelligent Designers in the UK now seem to be promoting the Krebs Cycle as evidence of Intelligent Design (see the Wikipedia entry at http://en.wikipedia.org/wiki/Citric_acid_cycle for some background in the Cycle)

My understanding is that some of the IDers have been pushing the Krebs Cycle for some years.

.Talk Origins has a substantial but very turgid entry which debunks the ID position on the Krebs Cycle. ( http://www.talkorigins.org/origins/postmonth/dec99.html).

However, I am unable to find any good debunking of the ID position. Can anyone help?
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Postby molecanthro » Tue Mar 06, 2007 12:33 pm

This all comes about from Behe (of course).

There's a mention of it in this paper by Niall Shanks (the person that wrote "God, the Devil, and Darwin," a critique of ID)
http://www.asa3.org/ASA/topics/Apologetics/POS6-99ShenksJoplin.html


And this article by Ken Miller addresses it briefly.
http://www.millerandlevine.com/km/evol/design1/article.html

Just search for Krebs in those papers.

Annoyingly, this is one of the main "complex" biomolecular systems that has been explained by evolutionary theory.

This is one of the main papers that's cited for this:
http://www.springerlink.com/content/j8ur17mp987434g4/
"The puzzle of the Krebs citric acid cycle: Assembling the pieces of chemically feasible reactions, and opportunism in the design of metabolic pathways during evolution "
And that was back in 1996 and has been cited by numerous other papers. Just a quick search for "krebs citric acid cycle evolution" on scholar.google.com turns up many articles.

mark.
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Re: Krebs Cycle

Postby Timothy Chase » Tue Mar 06, 2007 6:24 pm

Roger Stanyard wrote:Krebs Cycle

The Intelligent Designers in the UK now seem to be promoting the Krebs Cycle as evidence of Intelligent Design (see the Wikipedia entry at http://en.wikipedia.org/wiki/Citric_acid_cycle for some background in the Cycle)

My understanding is that some of the IDers have been pushing the Krebs Cycle for some years.

.Talk Origins has a substantial but very turgid entry which debunks the ID position on the Krebs Cycle. ( http://www.talkorigins.org/origins/postmonth/dec99.html).

However, I am unable to find any good debunking of the ID position. Can anyone help?


I would assume that their position is simply that it is irreducibly complex - and that they in no way attempt to explain how it is formed. Therefore, their position is simply one of negative critique aimed at any naturalistic explanation of how it came into being. Responding to this critique would be responding to their position.

In any case, one article you might want to look at would be:

Redundant Complexity:
A Critical Analysis of Intelligent Design in Biochemistry.
Niall Shanks
http://www.don-lindsay-archive.org/creation/shanks.html


In essence, the Krebs cycle is simply one of many chemical oscillators out there - and therefore, instances of self-organisation. However, the simplest metabolism we had been able to propose in the past involved 30 steps. Now we are able to propose one with three steps - involving fairly simple reactants - something which could easily have arisen in a geochemical context.

For some informal material on it, please see:

Putting Life's Puzzle Together :: Astrobiology Magazine
http://www.astrobio.net/news/modules.ph ... e&sid=1961

ScienceDaily: Methane-belching Bugs Inspire A New Theory Of The ...
www.sciencedaily.com/releases/2006/05/060512204140.htm


PS

I have posted on it before with a reference to the tech article which is now available on the net, I believe.
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Postby Chris Hyland » Tue Mar 06, 2007 7:45 pm

I presume that the charge is that the pathway is irreducibly complex, ie every part is needed for it to function. I read a paper on the subject a few years ago that had this diagram in it:
Image
Which is a good demonstration of what's wrong with the whole idea of IC.
Last edited by Chris Hyland on Tue Mar 06, 2007 8:15 pm, edited 1 time in total.
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Postby Timothy Chase » Tue Mar 06, 2007 8:14 pm

The simplest metabolisms which are most likely the most ancient tend to exist in thermophiles. Looking at the above diagram provided by Chris, pyrococcus horikoshii might be a good candidate for an ancient metabolism. Of course, heat tends to be a problem for both DNA and RNA, causing them to degrade over much shorter periods of time. However, certain environments, including those with high salt content will protect the nucleics against heat.

See for example:

Islas, et al. wrote:Since high salt concentrations protect DNA and RNA against heat-induced damage [26, 46], this and other non-biological mechanisms, such as adsorption to minerals surfaces and formation of clay–nucleic acid complexes [15] might have played a significant role in the preservation of organic compounds and genetic polymers in the primitive environments."

Hyperthermophily and the origin and earliest evolution of life
Sara Islas * Ana M. Velasco * Arturo Becerra
Luis Delaye * Antonio Lazcano
Int Microbiol (2003) 6: 87–94


Incidently, pyrococcus horikoshii is mentioned there.
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Postby Derek Potter » Thu Mar 08, 2007 10:57 am

Timothy Chase wrote:The simplest metabolisms which are most likely the most ancient tend to exist in thermophiles. Looking at the above diagram provided by Chris, pyrococcus horikoshii might be a good candidate for an ancient metabolism. Of course, heat tends to be a problem for both DNA and RNA, causing them to degrade over much shorter periods of time. However, certain environments, including those with high salt content will protect the nucleics against heat.

See for example:

Islas, et al. wrote:Since high salt concentrations protect DNA and RNA against heat-induced damage [26, 46], this and other non-biological mechanisms, such as adsorption to minerals surfaces and formation of clay–nucleic acid complexes [15] might have played a significant role in the preservation of organic compounds and genetic polymers in the primitive environments."

Hyperthermophily and the origin and earliest evolution of life
Sara Islas * Ana M. Velasco * Arturo Becerra
Luis Delaye * Antonio Lazcano
Int Microbiol (2003) 6: 87–94


Incidently, pyrococcus horikoshii is mentioned there.

I'm not up on this stuff. Is there much evidence to show that modern thermophiles have conserved metabolic cycles for billions of years? Is there actual evidence that they are not degenerate survivers? I know its nice to think we have a few billion years in which to improve a primitive cycle but does just one order of magnitude help? Why shouldn't there have been a big explosion of experimental chemistry lasting millions of years once cells had got the hang of staying in one piece? Remember that bloody beetle that blew itself up? I don't mean him.
.
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Postby Timothy Chase » Thu Mar 08, 2007 11:09 pm

derekpotter wrote:I'm not up on this stuff. Is there much evidence to show that modern thermophiles have conserved metabolic cycles for billions of years? Is there actual evidence that they are not degenerate survivers? I know its nice to think we have a few billion years in which to improve a primitive cycle but does just one order of magnitude help? Why shouldn't there have been a big explosion of experimental chemistry lasting millions of years once cells had got the hang of staying in one piece? Remember that bloody beetle that blew itself up? I don't mean him.
.

One could probably check by comparing with the rest of the family tree. Obligatory parasites, for example, tend to be real degenerates. Likewise, class III introns are degenerates of class II, so that sort of thing does happen. I still think there are some pretty big gaps in our understanding of archaea, too. However, if the archaea are not obligatory parasites, I at least would expect the simpler metabolisms to be more ancient.

However, a good article to check would be:

The puzzle of the Krebs citric acid cycle: Assembling the pieces of chemically feasible reactions, and opportunism in the design of metabolic pathways during evolution
Enrique Meléndez-Hevia, Thomas G. Waddell and Marta Cascante3
Journal of Molecular Evolution, Volume 43, Number 3 / September, 1996, pp. 293-303


The article came up in BCSE Chat, and it sounds pretty interesting, but to get it will probably require a visit to the library - or a subscription.


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Postby Derek Potter » Fri Mar 09, 2007 12:28 am

Timothy Chase wrote:However, if the archaea are not obligatory parasites, I at least would expect the simpler metabolisms to be more ancient.

Why?
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Postby Timothy Chase » Fri Mar 09, 2007 3:26 am

There are several reasons, although none of them are sufficient to conclude that, for example, the simplest metabolism is the most ancient - not that I would argue for this in any case. But what I would expect, generally speaking, is that the simpler the chemistry and the fewer the steps, the more likely that the metabolism is ancient, for the following reasons:

1. Metabolisms tend to be fairly complex. However, a metabolism of some sort had to exist very close to the origin of life itself - assuming one does not define life as requiring a metabolism. As such, it is likely that it would have arisen from geochemical processes which such primitive life would have been dependent upon prior to developing a metabolism of its own. and which are typically far simpler than the metabolic paths the evolution of life eventually gave rise to.
2. Alternatively, if a metabolism is regarded as essential to life, then it would have to coincide with life's origin, in which case it would have to begin as a geochemical process and would have to be simple enough that it could be stable to the point that life could survive long enough to evolve something more complex and robust.
3. The more complex the metabolism, the more likely it will be to be locked into doing at least some things a certain way due to various interdependencies - which means that these become added levels of complexity which can no longer be thrown away.
4. In silico at least, where selection isn't that great a force, protein paths tend to become more complex over time, and it seems reasonable to think that the same would hold true of metabolic paths.
5. In economics, programming and other fields, efficiencies are achieved through indirection - where by definition, indirection means added complexity. However, once more efficient means are discovered, reverting to less efficient means of survival would be selected against.
6. The more complex the metabolism, the more resources an organism potentially has to fall back on in a changing environment.
7. Evolution is itself a discovery process, comparable in some respects to a process of diffusion, and if there are simpler processes for achieving the same ends, then one would expect those simpler processes to be discovered first.

However, I must admit that I do not know where I got the figure for thirty steps (see above) from. It was something that I had (mis-)remembered, I believe in relation to the step-wise metabolic theory of House and Ferry - where they discovered a metabolic path in methanosarcina acetivorans requiring only methane, acetate, and carbon monoxide in addition to two fairly ancient enzymes.

The Stepwise Evolution of Early Life Driven by Energy Conservation
James G. Ferry and Christopher H. House
Molecular Biology and Evolution 2006 23(6):1286-1292
http://mbe.oxfordjournals.org/cgi/conte ... /23/6/1286
(abstract only)

An unconventional pathway for reduction of CO2 to methane in CO-grown Methanosarcina acetivorans revealed by proteomics
Daniel J. Lessner, Lingyun Li, Qingbo Li, Tomas Rejtar, Victor P. Andreev, Matthew Reichlen, Kevin Hill, James J. Moran, Barry L. Karger, and James G. Ferry
PNAS | November 21, 2006 | vol. 103 | no. 47 | 17921-17926
http://www.pnas.org/cgi/content/abstract/103/47/17921
(abstract only)

Oddly enough, acetivorans is a fairly big bug, genome-wise, at least, but it seems to have preserved some very simple, ancient metabolic paths - although it has a variety of others.

In any case, other research (see for example "The puzzle of the Krebs..." mentioned above) demonstrates that the Krebs is itself composed of parts which correspond to less complex cycles - and thus the Krebs is anything but an instance of irreducible complexity. And this suggests that...


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Postby Derek Potter » Fri Mar 09, 2007 9:10 am

Timothy Chase wrote:However, once more efficient means are discovered, reverting to less efficient means of survival would be selected against.
But that's what I'm querying. Environments are not static, and what is essential to survival under lean conditions can become a cumbersome contraption in times of plenty. Hence degeneracy.

The more complex the metabolism, the more resources an organism potentially has to fall back on in a changing environment.
We're talking about life which has only just discovered metabolism. Adaptability is a bonus that may well have evolved separately. You cannot assume that a complex metabolism that makes the most of food is necessarily going to be more adaptable at the prototype stage. For example, presumably the modern Krebs cycle can accept feeds at various points from several pathways. Not much use until those pathways and sources exist.

Evolution is itself a discovery process, comparable in some respects to a process of diffusion, and if there are simpler processes for achieving the same ends, then one would expect those simpler processes to be discovered first.
Actually no. Simplicity can be the end result of selection for, well simplicity. A horribly complex and inefficient process that uses really crappy but pre-existing catalysts might do the job very nicely at first. In fact your argument sounds like not-quite-Irreducible Complexity!

I'm not arguing for one scenario or another, just asking whether there is evidence of this linear progression that you imply or whether, as I suggested, it's possible that all sorts of things were invented in a rush at the very early stages of cellular life. I'm asking how well we understand the very first cellular family tree.

Oddly enough, acetivorans is a fairly big bug, genome-wise, at least, but it seems to have preserved some very simple, ancient metabolic paths - although it has a variety of others.
What about simple recent paths and complex ancient ones?

In any case, other research (see for example "The puzzle of the Krebs..." mentioned above) demonstrates that the Krebs is itself composed of parts which correspond to less complex cycles.
That is what I would have expected intuitively regardless of the degeneracy hypothesis.
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Postby Timothy Chase » Fri Mar 09, 2007 10:02 am

derekpotter wrote:But that's what I'm querying. Environments are not static, and what is essential to survival under lean conditions can become a cumbersome contraption in times of plenty. Hence degeneracy.

If the environment is variable, then those which slim down during times of plenty will find that they suddenly have to respond to leaner conditions - or so I would presume. But then they would no longer have the resources to respond. Given this, I would expect a larger potential repertoire to be selected for - within a variable environment.

derekpotter wrote:We're talking about life which has only just discovered metabolism. Adaptability is a bonus that may well have evolved separately. You cannot assume that a complex metabolism that makes the most of food is necessarily going to be more adaptable at the prototype stage. For example, presumably the modern Krebs cycle can accept feeds at various points from several pathways. Not much use until those pathways and sources exist.

I would argue that adaptability comes later - from a more complex metabolism which has available more pathways and more potential sources of energy. But remember: I am claiming that a simpler metabolism came first - and that more complex metabolisms were selected for.

Derek Potter wrote:Actually no. Simplicity can be the end result of selection for, well simplicity. A horribly complex and inefficient process that uses really crappy but pre-existing catalysts might do the job very nicely at first. In fact your argument sounds like not-quite-Irreducible Complexity!

Not quite - I am simply arguing general trend here - not that further efficiencies couldn't be achieved at certain steps by throwing away that which is no longer necessary.

Would it seem more reasonable that the original metabolism was more complex than what find in most bacteria today? Or that the general trend would have been towards simpler metabolisms with a smaller repertoire? If so, how could the original metabolism have arisen?

Derek Potter wrote:I'm not arguing for one scenario or another, just asking whether there is evidence of this linear progression that you imply or whether, as I suggested, it's possible that all sorts of things were invented in a rush at the very early stages of cellular life. I'm asking how well we understand the very first cellular family tree.

Well, I used qualifiers of "probably" and "I would at least expect." Basically, I was expressing a personal opinion, although judging from the analyses which I have seen, it seems on-spot, just not something I was prepared to cite - as there is too much to cite given the number of topics I try to track - and I was making what was essentially an off-the-cuff remark.

But I had also suggested that we check the family tree - which is the real, hard data - more or less. The experts have their phylogenetic analyses based upon genes, proteins, homologous protein structures (even when the amino acids show a great deal less homology - such as the fusion protein found in many virii). But it turns out that such gene transfer may make it more difficult to perform phylogenetic analyses of metabolisms...

[Wipes egg off face]

Gene transfer more common than we thought among archaea.. often involving genes that are linked metabolically.

The author wrote:They found that more than half of all the most primitive organisms, Archaea, have one or more protein genes acquired by horizontal gene transfer, as compared to 30 to 50 percent of bacteria that have acquired genes this way. Fewer than 10 percent of eukaryotes - plants and animals - have genes acquired via horizontal gene transfer....

"Our study shows that gene transfer is fairly common, but the extent in a given organism is fairly low - that is, most organisms have received one or more genes from a closely related organism. And while it's very likely that genes are transferred in chunks that are linked metabolically, I bet it's not always true. If a group of genes doesn't have value in a new environment for a new organism, it's not going to stick around."

Genes and groups of genes commonly shared between species, studies show
Sharing genes likely helps organisms adapt more quickly to new environments
Public release date: 8-Mar-2007
http://www.eurekalert.org/pub_releases/ ... 030807.php

However, while there is gene transfer, it tends to be greater among related species (see above), so it wouldn't seem to make such analyses much more difficult. And the fact that lateral gene transfer tends to occur more often between closely related species is something I would expect - although it can occur between distantly-related species - but this is much more rare.

Actually, I am beginning to follow these people. One of the more recent research involved apparently free-living nanoarchaea in a highly acidic environment.

Here is the press article:

Nanoorganisms: Probe Of Acid Mine Drainage Turns Up Unsuspected Virus-sized Archaea
Date: December 22, 2006
http://www.sciencedaily.com/releases/20 ... 092509.htm


... and here is the tech:

Lineages of Acidophilic Archaea Revealed by Community Genomic Analysis
Brett J. Baker, Gene W. Tyson, Richard I. Webb, Judith Flanagan, Philip Hugenholtz, Eric E. Allen, Jillian F. Banfield


Anyway, it is about time for me to go to bed - perhaps two or three hours ago.
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Postby Timothy Chase » Fri Mar 09, 2007 10:06 am

PS

Incidently, methods are improving so that we will be able to generate more accurate trees with less data due to the prevailence of "microinversions" and two complementary methods - where one handles deletions well, but does poorly at detecting insertions, and the other handles insertions well, but does poorly at detecting deletions. I will have to look up the material - a little later.
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Postby Derek Potter » Fri Mar 09, 2007 11:16 am

Timothy Chase wrote:Would it seem more reasonable that the original metabolism was more complex than what find in most bacteria today? Or that the general trend would have been towards simpler metabolisms with a smaller repertoire?
Well, yes, actually. The absolute earliest evolution must have been from simple to complex but there's no immediate reason to assume that subsequent evolution didn't involve simplification for some organisms, leaving a simple metabolism but one which is unrelated to the earliest steps.

A extinct
AB
ABC
ABCD
ABCDE
BCDE
CDE
DE
E survives

This hypothesis would suggest that the place to look for the very earliest metabolisms is buried within the most complex modern ones, not in highly specialized, but simplified survivors!

AFAIK, the family tree is obscure at the "roots" but if they have evidence that definitely goes back to the very first cells ("A" rather than "CDE" for example), then that is quite something.
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Postby Timothy Chase » Fri Mar 09, 2007 5:31 pm

derekpotter wrote:
Timothy Chase wrote:Would it seem more reasonable that the original metabolism was more complex than what find in most bacteria today? Or that the general trend would have been towards simpler metabolisms with a smaller repertoire?
Well, yes, actually. The absolute earliest evolution must have been from simple to complex but there's no immediate reason to assume that subsequent evolution didn't involve simplification for some organisms, leaving a simple metabolism but one which is unrelated to the earliest steps.

Some simplification for some organisms, but how much simplification and how late in the game? Probably not a great deal of simplification particularly late in the game. However, what is probably one of the earliest metabolisms is "buried" within one of the more complicated archaea - methanosarcina acetivorans - except of course we have "uncovered" it. However, my argument wasn't so much about the complexity of the organism, but the complexity of the metabolism - although it probably would have been more accurate to say "metabolic path."

However, simpler metabolisms should come earlier because later metabolisms will generally result in increased efficiencies and robustness - and likewise, particularly stable environments which are conducive to the simplification of a metabolism should become occupied earlier rather than later.

All of these are points I made in:

http://bcseweb.org.uk/forum/viewtopic.php?p=7783#7783

But I also suggested in:

http://bcseweb.org.uk/forum/viewtopic.php?p=7781#7781

... that the best way to answer these questions is with actual research.

As for the roots being obscure - certainly at this point. But I believe that with the appropriate phylogenetic and geochemical analysis we will be able to make a fairly strong argument. However, I am probably more optimistic than some - although given some of the recent discoveries perhaps I have a some reason to be.
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Postby Timothy Chase » Fri Mar 09, 2007 6:04 pm

PS

The metabolic path discovered methanosarcina acetivorans is quite possibly simple enough to have been the original metabolism, and while the bug currently uses two fairly complicated enzymes to perform its trick, it is quite possible that a mineral catalyst could have performed the same - given the environment that they are proposing.

But of course this is still fairly speculative.
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