The Left Hand of Darwin

Posted by John S. Wilkins on June 28, 2004 09:44 PM

One long-standing question in understanding the origin of life is the so-called “chirality problem”. While this is an unresolved question in our understanding of the origin of life, it is used by anti-evolutionists to beat evolutionary theory over the head. As we never tire of telling folk, the origin and subsequent evolution if life are two distinct issues.

What is the “chirality problem”? Let’s start by briefly discussing what chirality is. Biological molecules of some complexity often come in two forms that while chemically identical, have different three dimensional shapes; a “left-handed” one, and it’s mirror image, a “right-handed” one (see alanine graphic). Of particular importance for living systems are amino acids (levo- or left-handed) and sugars (dextro- or right-handed). Handedness is due to the carbon atom’s bonding capacities. This property of some molecules was discovered in 1847 by none other than Louis Pasteur (the molecule was a form of tartrate) in the dregs of some wine.

[img][*]http://www.pandasthumb.org/pt-archives/L-alanine.jpg…[*]http://www.pandasthumb.org/pt-archives/D-alanine.jpg…[/img]
Chiral forms (enantiomers) of the amino acid alanine. White balls are hydrogen atoms, grey balls are carbon atoms and the red ball is an oxygen atom, The left handed form is not superimposable on the right handed form).

How, it is asked, could this have occurred at the beginning of life? Surely ordinary physical processes should have given us a mix of both left and right handed forms (known as a racemic mixture)?

Well, firstly it turns out that ordinary physical processes do produce an excess of left over right forms. Recently, though, it was discovered that life itself can generate a particular enantiomer or chiral form of a particular molecule.

This shouldn’t surprise us. The mechanism proposed is a simple one, and one that is expected in biological processes - catalysis. Molecules in biological processes are often formed by the mediation of a separate catalyst. If the catalyst itself is the product of biological processes, the reaction cycle is called autocatalytic. It seems that amino acids are indeed the result of autocatalysis.

The idea, proposed 50 years ago by F. C. Frank, was experimentally observed and demonstrated by a Japanese research group headed by Kenso Soai at Tokyo University in 1995, but they used an inorganic catalyst.

Now, Professor Donna Blackmond, Professor of Catalysis at the Imperial College and her colleagues have seen it happen via the catalytic effects of proline, an amino acid, in vivo. As proline is produced by biological processes, this counts as a bootstrapping case of autocatalysis. If a single form gained currency by being reproduced, other forms would be less efficient, and eventually  all living things that evolved from the first form would follow suit. In evolutionary theory and in other fields, this is called a “frozen accident” theory.

We know that amino acids need not be levo, because dextro-amino acids have been used to make functional proteins.

We will surely see similar processes that explain how sugars are dextro (right handed) in the future. Indeed, we already have. Gary Hurd sent me these references:

Pizzarello, Sandra, Arthur L. Weber. 2004 Prebiotic Amino Acids as Asymmetric Catalysts Science Vol 303, Issue 5661, 1151, 20 February 2004

This paper examined the effect of handed amino acids on the production of sugar, noting that meteorites that fall to earth show a preference for levo-amino acids, just as we have on earth. They concluded that the amino acids catalyse chiral dextro sugars.

Ricardo, A., Carrigan, M. A., Olcott, A. N., Benner, S. A.. 2004 “Borate Minerals Stabilize Ribose” Science January 9; 303: 196

This paper notes that if borate is used to form pentose sugars (such as ribose, the sugar that is part of RNA), these sugars are the dextro form found in living things.

Sephton, Mark A. 2001 Meteoritics: Life’s sweet beginnings? Nature 414, 857 - 858 (20 Dec)

And this paper shows that dextro sugars and related compounds form in space, based on a couple of meteorites that fell to earth, one not far from my home in south-eastern Australia.

As with most anti-evolutionary arguments, the “chirality problem” one has relied on what we don’t know yet. Wesley Elsberry and I argued against William Dembski’s “Design Inference” that what he lacked there, too, was a “don’t know yet” branch on his decision tree. It is indeed an argument from ignorance, and it is not how science makes progress of any kind.

I wonder what we’ll discover next, that makes such arguments unnecessary…

Thanks to Steve Reuland and Ian Musgrave for preventing me from looking like I didn’t know a pentose sugar from a chocolate bar. Ian provided the molecule images of the D and L alanine based on Chime images found here (requires Chime) you may need to rotate them so the mirror images line up properly

Trackback URL: http://www.pandasthumb.org/cgi-bin/mt/mt-tb.cgi/294

Comment #4306

Posted by Russell on June 27, 2004 10:31 PM (e) (s)

(The blue balls in the picture are nitrogen. Just in case anyone was losing sleep over it)

Comment #4307

Posted by Kip Manley on June 28, 2004 12:14 AM (e) (s)

Thank you, Russell. Not losing sleep, per se, but not unconcerned, either. —This handedness stuff is also well-known to fans of pulpy SF: someone gets folded into a mirror image of themselves through contact with a higher dimension, and so now must make use of left-handed sugars and right-handed amino acids, which are impossible to find, or, as it turns out, quite desperately rare, and so they starve to death, with food all about them. As a trope, it has whiskers, and really ought to be retired.

Comment #4311

Posted by Anton Mates on June 28, 2004 01:09 AM (e) (s)

A 2000 paper in Nature pointed out that those first (perhaps very slight) imbalances in chirality could have been due to one form’s being preferentially broken down by light, when in an ambient magnetic field.

Rikken, G. L. J. A. & Raupach, E. Enantioselective magnetochiral photochemistry. Nature 405, 932 - 935 (2000)

Whether they formed on Earth or in space, those primordial organics were probably exposed to a magnetic field, so this is a pretty compelling explanation of their initial handedness bias.

(I also recall a paper on preferential breakdown by circularly polarized light, without considering magnetic fields…the authors suggested neutron stars as a possible source of such light.)

The <i>total</i> domination of one chiral form we see now, of course, requires the sort of self-amplification Professor Blackmond demonstrated.

Comment #4324

Posted by Paul Orwin on June 28, 2004 01:36 PM (e) (s)

Just as a side note, bacteria use many D-amino acids in their cell walls (not as part of the formation of proteins).  Penicillin, in fact, attacks an enzyme called a PBP (inaptly, a penicillin binding protein) which is a D-alanine transpeptidase, involved in the transfer of a D-alanine peptide bond from another D-ala to  meso-diaminopimelic acid (a diamino acid) to form the structural cross-bridge in the bacterial cell wall (called Peptidoglycan, or murein).  Since by most estimates prokaryotes make up the vast majority of the earth’s biomass, and the PG layer is a significant fraction by wt, I submit that D-amino acids are not in the least rare in biology.

Comment #4325

Posted by Gary Hurd on June 28, 2004 01:38 PM (e) (s)

The selective enhancement of one enanantiomer over another by uv light in outer space has been fairly well discussed and sources of this light have been identified:

Nishino, H. et al.,
2001 Mechanism of pH-dependent photolysis of aliphatic amino acids and enantiomeric enrichment of racemic leucine by circularly polarized light, Organic Letters 3(6):921-924, March 22,

Chyba, Christopher F.
1997 Origins of life: A left-handed Solar System? Nature 389, 234- 235 (18 Sep 1997)

GM MUÑOZ CARO, UJ MEIERHENRICH, WA SCHUTTE, B BARBIER, A
ARCONES SEGOVIA, H ROSENBAUER, WHP THIEMANN, A BRACK & JM
GREENBERG
2002 Amino acids from ultraviolet irradiation of interstellar ice analogues. Nature 416, 403 - 406 (2002)

J. Bailey
2001  “Astronomical sources of circularly polarized light and the origin of homochirality” Origins of Life and Evolution of the Biosphere 31(1-2): 167-183, Feb-Apr,

Antonio Chrysostomou, T. M. Gledhill,1 François Ménard, J. H. Hough, Motohide Tamura and Jeremy Bailey
2000 “Polarimetry of young stellar objects - III. Circular polarimetry of OMC-1” Monthly Notices of the Royal Astronomical Society Volume 312 Issue 1 Page 103 - February

The data supporting the idea that these amino acids did in fact reach the Earth are from direct analysis of meteorite such as:

Michael H. Engel and Bartholomew Nagy,
1982 “Distribution and Enantiomeric Composition of Amino Acids in the Murchison Meteorite”, Nature 296, April 29, p. 838.

Chronin, John R., Sandra Pizzarello
1997 “Entantiomeric Excesses in Meteoritic Amino Acids” Science Vol. 275:951-955

Chronin, J. R. & Pizzarello, S., 1999. Amino acid enantomer excesses in meteorites: Origin and significance. Advances in Space Research 23(2): 293-299.

Engel, M. H., S. A. Macko
1997 Isotopic evidence for extraterrestrial non- racemic amino acids in the Murchison meteorite. Nature 389, 265 - 268 (18 Sep) Letters to Nature

There are several ways that this small excess of L- amino acids would have driven the ultimate (nearly) homochiral life on Earth:

Schmidt, J. G., Nielsen, P. E. & Orgel, L. E.
1997 Enantiomeric cross-inhibition in the synthesis of oligonucleotides on a nonchiral template. J. Am. Chem. Soc. 119, 1494-1495.

Blackmond, Donna
2004 Asymmetric autocatalysis and its implications for the origin of homochirality. Proceedings of the National Academy of Sciences of the United States of America (2004 Apr 20), 101(16), 5732-6.

Gridnev Ilya D; Brown,  John M
2004  Asymmetric autocatalysis: novel structures, novel mechanism?. Proceedings of the National Academy of Sciences of the United States of America (Apr 20), 101(16),
5727-31

Saghatelion A, Yokobayashi Y, Soltani K, Ghadiri MR,
2001”A chiroselective peptide replicator”, Nature 409: 797-51, Feb

Singleton DA, Vo LK.
2003  A few molecules can control the enantiomeric outcome. Evidence supporting absolute asymmetric synthesis using the Soai asymmetric autocatalysis.  Org Lett. (Nov 13);5(23):4337-9.

I want to thank Anton for the reference to the paper in Nature, as it slipped by me.  There is another mechanism that I think is operating that has apparently been overlooked, and that is the greater stability of an enantiomer when it is part of a larger molecule.  The rate that amino acids ‘convert’ from one form, L- or D-, to another (called racemization) varies for each amino acid and by temperature, and humidity.  When amino acids are bound in larger molecules, and especially when these molecules are bound to a metal, the rate of both polymer diagenesis and amino acid racemization is reduced.  This, coupled with the chiral selective reactions cited above, will create a persistant chrial ‘pool’ of avialable molecules. Another recent paper by Blackmond, “Asymmetric autocatalysis and its implications for the origin of homochirality.” PNAS-USA (2004 Apr 20), 101(16), 5732-6, points out that this chiral pool will also be facilitated by the relative instability of mixed L- and D- polymers.

Comment #4337

Posted by Mr George on June 28, 2004 09:38 PM (e) (s)

I was reading about this topic a few months ago, unfortunately I can’t remember many of the details, but I think it was a paper in the journal Origins Life Evol. Biosphere. Apparently certain clays can catalyze the production of molecules, such as RNA, that are thought to be the precursors to life. The researchers showed that the clays catalyzed one chirality more than another. I did a quick google search but couldn’t find the paper again. I think it is pertinent to this discussion so can anyone else provide the reference?

Mr George
The University of Western Australia

Comment #4341

Posted by Gary Hurd on June 28, 2004 10:39 PM (e) (s)

Well, there is:

Hazen, R.M., T.R. Filley, and G.A. Goodfriend.
2001. Selective adsorption of L- and D-amino acids on calcite: Implications for biochemical homochirality. Proceedings of the National Academy of Sciences 98 (May 8):5487.

But calcite is not a clay.  More likely you are thinking of montmorillonite:

Martin M. Hanczyc, Shelly M. Fujikawa, and Jack W. Szostak
2003 Experimental Models of Primitive Cellular Compartments: Encapsulation, Growth, and Division Science October 24; 302: 618-622. (in Reports)

From the abstract:
“The clay montmorillonite is known to catalyze the polymerization of RNA from activated ribonucleotides. Here we report that montmorillonite accelerates the spontaneous conversion of fatty acid micelles into vesicles. Clay particles often become encapsulated in these vesicles, thus providing a pathway for the prebiotic encapsulation of catalytically active surfaces within membrane vesicles. In addition, RNA adsorbed to clay can be encapsulated within vesicles.”

Comment #4347

Posted by Prem Janardhan on June 29, 2004 12:38 AM (e) (s)

So man was partially formed from clay (probably).

Comment #4385

Posted by Mark Isaak on June 29, 2004 11:09 PM (e) (s)

Another amplification method is reported in:

Zepik, H. et al., 2002.  Chiral amplification of oligopeptides in two-dimensional crystalline self-assemblies on water.  Science 295: 1266-1269.

Comment #4386

Posted by Mark Isaak on June 29, 2004 11:12 PM (e) (s)

Another amplification method is reported in:

Zepik, H. et al., 2002.  Chiral amplification of oligopeptides in two-dimensional crystalline self-assemblies on water.  Science 295: 1266-1269.

Comment #4407

Posted by Nick on June 30, 2004 11:00 PM (e) (s)

Just as a side note, bacteria use many D-amino acids in their cell walls (not as part of the formation of proteins).  Penicillin, in fact, attacks an enzyme called a PBP (inaptly, a penicillin binding protein) which is a D-alanine transpeptidase, involved in the transfer of a D-alanine peptide bond from another D-ala to  meso-diaminopimelic acid (a diamino acid) to form the structural cross-bridge in the bacterial cell wall (called Peptidoglycan, or murein).  Since by most estimates prokaryotes make up the vast majority of the earth’s biomass, and the PG layer is a significant fraction by wt, I submit that D-amino acids are not in the least rare in biology.

I have seen it suggested by competent authorities that the presence of D-amino acids in cell walls might have originated early in cell evolution, as a method of sequestering them to get them out of the way.  On this model, they were coopted to build the cell wall and once the cell wall became a crucial competitive advantage, bacteria became dependent on it and on D-amino acids.  As D-alanine would probably be the most common prebiotic D-amino acid (Glycine, the most common amino acid, is the one achiral amino acid), this model makes some sense.  I have no idea if features such as the modern biosynthetic pathway for D-alanine tends to support the model or not.

Comment #4491

Posted by Gary Hurd on July 3, 2004 12:13 PM (e) (s)

I am glad that John started this topic, as I have picked up some good referemnes(Thanks Anton and Mark). 

The notion about D-alanine being “the most common prebiotic D-amino acid” eludes me.  Is there something I could read on this?  The existance of racemate enzymes (including one for L-alanine) seems to me to indicate that this is a late(er) inovation to cell walls.  I see a possible scenario: early cell  walls evolve with both L- and D- amino acids, the availability of D- forms is reduced, bacteria which evolve an enzyme that changes L- to D- survive while others evolve all L- cell walls.

In several ways this would be a very nice solution.  I still wonder though.

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