Matt Brauer posted Entry 1764 on December 15, 2005 03:14 PM.
Trackback URL: http://www.pandasthumb.org/cgi-bin/mt/mt-tb.fcgi/1759

plosRobinson0511.jpg
In my last post I mentioned in passing the feature article appearing in November’s issue of PLoS biology.

In that paper, Richard Robinson describes some of the difficulties faced by researchers into the Origin of Life. The origin of replicating molecules is a question of intense interest to biologists because replication is the required (and perhaps sufficient) condition for subsequent evolution. (“Give biologists a cell and they’ll give you the world” is how Robinson puts it.)

The fundamental breakthrough in Origin of Life (OoL) research came, of course, from the famous Miller-Urey experiment, in which it was shown that energy applied to mixtures of inorganic compounds could lead to the formation of biologically significant molecules. Despite problems that later emerged in Miller and Urey’s model, the fundamental point always remained that some conditions exist that can result in the spontaneous origin of organic molecules.

But it’s a big long step from organic chemistry to biochemistry. The existence of biochemical precursors such as nucleotides and amino acids need not imply the development of replicating RNA and proteins. One of the biggest hurdles faced by OoL research is the fact that modern life at some point incorporated the dichotomy between replicating molecules and the effector molecules they code for. Life (the objection goes) would have had to develop two distinct but wholly dependent systems simultaneously. It is safe to say that this scenario is so unlikely that it is effectively impossible.

Life as we know it is not life as it has always been, however. Jack Szostak’s discovery that RNA needn’t be just a medium for the genetic code, but that it might also itself be an effector molecule, led to one solution to OoL’s chicken-and-egg problem. Szostak postulated that modern biology developed from an “RNA World”. In the precursors to modern cells, RNA was supposed to act both as replicator and as an enzyme, so that there was no need for a parallel and simultaneous origin of multiple complex systems. The Origin of Life via the RNA World is a “genes first” model, in which the replicator arose and gradually evolved by improving its autocatalytic replication activity.

The RNA World has problems of it own, of course, and various alternatives have been proposed to deal wih these. One model, based on “Peptide Nucleic Acids” (PNA), suffers from many of the same deficiencies that challenge the RNA World. But there is growing excitement about the idea that metabolic function might have preceded replicative function. These “metabolism first” models take recent discoveries about chemistry on surfaces and extrapolates to the conditions that might have characterized the early earth. The basic idea is that enzymes act simply by providing surfaces on which favored chemical reactions can occur. If the surface is what is important, why couldn’t an inorganic molecule provide this just as well. In fact, many modern metabolic enzymes require as cofactors so-called “Iron-Sulfur clusters”. In essence, the enzyme is simply a device for capturing a minute piece of the original crystalline surface, and making it available at the right place and time. (My favorite enzyme of the moment, Aconitase, is one of these Fe-S enzymes).

“Metabolism first” models imagine a porous crystalline structure through which reactants percolate, and within which polymerized products are captured. There’s a fair bit of handwaving involved in describing the next steps in the development of life, but the basic idea is nevertheless intriguing.

There are enormous gaps in all Origin of Life models. But these gaps ought to be expected: we’re talking about a singular event that happened 5-6 BYA, after all. Still, progress in the models continues. And, more importantly, Origin of Life research has resulted in profound insights into basic biochemistry that have generated phenomenally productive research programs.

In the end, even if all of our best current models are gross simplifications (as they most certainly are), their testing and refining have led to a much deeper understanding of what we mean when we speak of “life”.

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Comment #63008

Posted by Steviepinhead on December 15, 2005 3:32 PM (e)

One suspects this all happened closer to 4-4.3 billion years ago, unless the “singular event” occurred somewhere else in the solar system or galaxy, and the resulting replicators drifted/smashed into good ol’ Terra later on.

Otherwise a good summary of a good summary! And thanks again for rounding up the links and sharing with the rest of the pandas!

Comment #63009

Posted by Piggy's got the conch on December 15, 2005 3:37 PM (e)

One of the problems noted in that article was the difficulty of getting funding for OoL research. It mentions that Harvard has recently committed one million dollars a year for the purpose, but that it was only “a good start”.

How much money does the DI receive every year? It seems to me this would be something they would be very interested in? What’s the hold-up?

Comment #63018

Posted by Bayesian Bouffant, FCD on December 15, 2005 4:24 PM (e)

Robinson notes the appreciable difference between eubacteria and archaea membrane lipid constitution, and mentions a hypothesis that they evolved independently and in parallel (as opposed to one evolving from the other)

If so, since all known cellular life shares common ancestry in their DNA-handling equipment, I think this would lead to the conclusion that both protein synthesis and the use of DNA preceded the development of membrane lipid metabolism.

Comment #63019

Posted by qetzal on December 15, 2005 4:29 PM (e)

If so, since all known cellular life shares common ancestry in their DNA-handling equipment, I think this would lead to the conclusion that both protein synthesis and the use of DNA preceded the development of membrane lipid metabolism.

Interesting point! I wonder if it’s possible to test this with molecular phylogenies?

Comment #63043

Posted by Dan Hocson on December 15, 2005 8:10 PM (e)

Somehow, I think that the DI already “knows” how life originated, so why bother doing any research?

Comment #63055

Posted by Jaime Headden on December 15, 2005 10:19 PM (e)

The DI is only concerned in how abiogenesis didn’t occur; the very issue of trying to see if and how it did occur is beyond their decision making mechanisms.

Comment #63058

Posted by Ian Musgrave on December 15, 2005 10:23 PM (e)

I would be wary of taking Richard Robinson’s paper too much to heart. It tends to exaggerate certain things, possibly to create a more “exciting” article, and is flat out wrong in some areas. For example, talking about “prebiotic soups”

Robinson wrote:

Finally, there is no geologic evidence, in either sediments or metamorphic rocks, that such a soup ever existed.

is wrong, because we just don’t have the appropriate rocks. We have no sedimentary rocks from the period between 4.4-3.8 Bya, when abiogenesis was occurring. In metamorphic rock all the organic carbon from a “prebiotic soup” would be broken down into either CO2 or traces of graphite. We do have traces of graphite in metamorphic rock from 3.8 Bya, but this material is claimed to be show the isotopic signatures of metabolism, so arguably post dates any “prebiotic soup”. As well, Robinson seems to think the “prebiotic soup” models were some sort of tick gumbo, when they were envisaged to be at quite modest concentrations.

The box on chirality is just plain wrong. There is a lot of work on production of chirality by the effects of UV light, assembly on mineral surfaces etc. The abiogenically produced Murchison meteorite amino acids are chirally enriched. Also, there is a rule in chemistry known as “The majority rule” whereby in a mixture of monomers with an enatomeric excess, polymers will be produced with a single handedness.

“Replicators first” models are conflated with heterotrophic metabolism models. The “growing excitement” about “metabolism first’ models is over played (while the growing excitement about advances in the RNA world models and advances in understanding where and how membrane encapsulation occurred is ignored).

Also, how could people possibly get outrageously excited over the idea that amino acids are catalysts by themselves. We know that already, it is a fundamental fact of chemistry and biochemistry that amino acids are catalysts (proteins are just more efficient ways to utilise amino acid catalysis). The paper (not cited in the article) “Cordova A, et al., Amino acid catalyzed neogenesis of carbohydrates: a plausible ancient transformation. Chemistry. 2005 Aug 5;11(16):4772-84.” shows that it is possible to produce high yields of near enationmerically pure D-sugars under certain conditions using proline, but proline will be at low concentrations in any plausible prebiotic environment, and more weakly chiral catalysis, like that produced by valine, is likely. This result is interesting, and add a bit to our store of knowledge about prebiotic chemistry and how chirality is produced.

Heterotophic reactions and mineral catalyzed metabolism are not mutually exclusive, they almost certainly occurred together on the early Earth. One of the take home messages of prebiotic research is how is it is to make the building blocks of life in many diverse environments by many mechanisms. Almost everyone agrees that the RNA word came after an earlier metabolic world of some sort. Robinson exaggerates some aspects of modern abogenesis research, and completely ignores others, in this rather disappointing article.

Comment #63059

Posted by CJ O'Brien on December 15, 2005 10:28 PM (e)

Yeah, I thought I had read somewhere a little better analysis of the Chirality “problem” and that box seemed like it was thrown in as an afterthought.
Great commentary, Mr. Musgrave. Thanks, from the peanut gallery.

Comment #63062

Posted by Timothy Chase on December 16, 2005 1:40 AM (e)

Matt Brauer wrote:

The fundamental breakthrough in Origin of Life (OoL) research came, of course, from the famous Miller-Urey experiment, in which it was shown that energy applied to mixtures of inorganic compounds could lead to the formation of biologically significant molecules. Despite problems that later emerged in Miller and Urey’s model, the fundamental point always remained that some conditions exist that can result in the spontaneous origin of organic molecules.

In this second paragraph, you refer to problems in the Miller-Urey experiment. By this do you mean that the early atmosphere was a neutral one rather than a reducing one? If so, are you familiar with the experiments by Bruce Fegley in late 2005 which suggest that the early atmosphere was in fact a reducing atmosphere?

Please see:

Reducing Early Earth

Comment #63063

Posted by Ed Darrell on December 16, 2005 1:47 AM (e)

Andy Ellington of the University of Texas gave a marvelous seminar to the Texas State Board of Education on abiogenesis issues, including a couple of minutes on chirality, back in 2003. Has anyone extracted that section from the .pdf files the SBOE has at their site?

Ellington followed Stephen Weinberg in the testimony chain. It was a fine hour of education – it’s not clear all the SBOE members were fully aware.

Comment #63065

Posted by Bruce Beckman on December 16, 2005 2:54 AM (e)

Ed, do you have a link to the Texas SBOE testimony .pdf?

Comment #63068

Posted by Daniel Morgan on December 16, 2005 7:02 AM (e)

I recently compiled some really good articles on my website in list fashion regarding abiogenesis. I specifically focused on publications reviewing homochirality and other frequently-touted “problems” for abiogenesis (mostly Bonner pubs). For those of you without the access or time to look them up, this could prove a valuable resource. Also, in one of the listed pubs, Lindahl, from TA&M, put together a very good review (2004) that takes us from organic chemistry to metabolism via “Quasi-steady state systems”…worth your read. Keep in mind that copyright laws apply to these full-text PDFs.

Comment #63069

Posted by Louis on December 16, 2005 7:04 AM (e)

Discussions of the origins of homochirality always seem to miss the possibility of autocatalysis, i.e. a reaction in which the product catalyses it’s own formation. For an example of one reaction that autocatalytically produces an enantiomeric excess, look up the Soai reaction.

Comment #63072

Posted by mmurphy21 on December 16, 2005 7:51 AM (e)

I see quote mining heaven in this article. How long will it take to see “One of the biggest hurdles faced by OoL research is the fact that modern life at some point incorporated the dichotomy between replicating molecules and the effector molecules they code for. Life would have had to develop two distinct but wholly dependent systems simultaneously. It is safe to say that this scenario is so unlikely that it is effectively impossible.” on an ID website.

Comment #63086

Posted by Bob on December 16, 2005 9:26 AM (e)

“5-6 BYA”

your igneramus

Comment #63088

Posted by jim on December 16, 2005 9:35 AM (e)

Bob wrote:

your igneramus

Umm, do you see the irony in your post?

Comment #63100

Posted by evopeach on December 16, 2005 11:01 AM (e)

Since the ultimate driving force for all evolutionary change is random mutation and therefore drawn from essentially uniform random distributions over the entire genomic probability space, how does one account for the universal distribution of traits, function, form etc. in all of nature being essentially normally distributed.

Evopeach

Comment #63113

Posted by Matt on December 16, 2005 11:39 AM (e)

Timothy Chase asks if my reference to “problems” in Miller-Urey was related to changes in assumptions about the composition of the early atmosphere. That is what I had in mind. As Tim points out, the jury is still deliberating on this question. (Thanks for the link, Tim!)

Evopeach wonders why the values of many traits are distributed normally, given that the distribution of mutations is uniform across the genome.

First, the distribution of mutations is not uniform across the genome. Even if it was, however, there is no reason to assume that this distribution would determine the distribution of trait values. You have to remember that selection acts to change the distribution of mutations, so that random in does not imply random out. More importantly there is no reason to imagine that the location of a mutation has any correlation with the value of the trait it influences.

Consider a quantitative trait (height, say) that involves a bunch of genes in an additive fashion. Each of these genes has two possible alleles: functional or non-functional. If you have functional alleles for all of the genes, you’ll be of maximum height, while non-functional alleles at all loci will result in the minimum height. It can be shown that with a large number of genes, height will be distributed approximately normally.

So even assuming that the chance of getting a functional or non-functional allele at a given gene was given by a uniform distribution, you’d still have a normal distribution in heights.

Comment #63114

Posted by djmullen on December 16, 2005 11:40 AM (e)

The paper (not cited in the article) “Cordova A, et al., Amino acid catalyzed neogenesis of carbohydrates: a plausible ancient transformation.

You scared the hell out of me there! For a moment, I thought Salvador had written something useful.

Comment #63115

Posted by steve s on December 16, 2005 11:43 AM (e)

No worries, dj, if Sal had written it, it would be

““Cordova S, et al., Amino acid catalyze neogenesis of carbohydrate’s: a plausable ancient trans-formation.”

Comment #63128

Posted by Steviepinhead on December 16, 2005 12:56 PM (e)

Ha! Now it turns out that Sal’s got a smarter “older brother!” One who actually performs and publishes scientific research!!

Sal’s lifelong envy of his more successful “sibling” clearly lies at the core of his anti-science sycophancy.

Beyond hilarious. Those who don’t peruse these pages regularly are missing out on a barrel of laughs.

Comment #63304

Posted by SetoKaiba on December 18, 2005 12:17 PM (e)

Are you a creationist Daniel Morgan? Why do you have Chance and Necessity do no explain the origin of life on your website? BTW, nice papers you have on your website!

Comment #63312

Posted by DrFrank on December 18, 2005 2:09 PM (e)

Evopeach:
Since the ultimate driving force for all evolutionary change is random mutation and therefore drawn from essentially uniform random distributions over the entire genomic probability space, how does one account for the universal distribution of traits, function, form etc. in all of nature being essentially normally distributed.

The Central Limit Theorem, maybe?

Comment #77042

Posted by danajohnson0 on February 2, 2006 11:44 AM (e)

At the risk of resurrecting an old thread, I should mention I have never posted on this site previously, and found the location in researching Jack Szostak’s pages in a search. I contribute to the Mars Rover Blog and was interested in any assistance there in identifying small details and item types which are becoming available in the Mars rover MI closeup photos still arriving over the past two years. Not to take you from a valuable site such as this, but the interest in possible evolutionary processes or complex crystallographic shaping controls is an ongoing interest to persons there as well. Segregation of biology ‘vs’ mineralogy/geology is being cultured there, leading to the routine separation of biology(life) and geology(dead) conceptually. Any takers? Forums, ‘Biology’,or ‘Open’, only, allowed currently.
Mars Rover Blog
The science (evidence) for the subject may be still present on Mars, rather than Earth.