Tuesday, June 16, 2009

Nicholas Wade on the Origin of Life

Nicholas Wade is a science journalist who writes for the New York Times. His particular area of expertise is evolution and molecular biology and he is often mentioned as one of the best science writers in America.

That's not an opinion that I share, although it's true that he writes very well.

Wade's latest article is New Glimpses of Life’s Puzzling Origins. The focus of this article is on recent discoveries in chemistry and biology relating to the origin of life. These all support a scenario where complex molecules in a warm little pond give rise to replicating nucleic acids enclosed in a membrane vesicle. Not much attention is paid to the competing scenarios—especially the one I favor: Metabolism First and the Origin of Life.

Now don't get me wrong. There's no reason why Nicholas Wade can't prefer one particular scenario for the origin of life. After all, many scientists agree with him. The problem I have is that when it comes to informing those who read newspapers, they won't be getting the full story.

One of the "problems" in origin of life studies is the "chirality" problem. The idea is to explain why life prefers left-handed amino acids instead of right-handed amino acids. The "problem" arises when you postulate that life arose in a soup consisting of equal amounts of both types of amino acid.

Sandwalk readers will know my opinion on the "problem." I think it's a "non-problem" since life probably didn't arise from a pool of 20 different concentrated amino acids. I prefer a scenario where a few simple amino acids contributed to the first catalysts and expansion of the repertoire of amino acids resulted from synthesis of more complex ones from simple ones. Since this was "biological" synthesis, the complex amino acids were all left-handed forms from the beginning because the precursors were already left-handed [Can watery asteroids explain why life is 'left-handed'?].

Let's see how Nicholas Wade describes recent results.
Another striking advance has come from new studies of the handedness of molecules. Some chemicals, like the amino acids of which proteins are made, exist in two mirror-image forms, much like the left and right hand. In most naturally occurring conditions they are found in roughly equal mixtures of the two forms. But in a living cell all amino acids are left-handed, and all sugars and nucleotides are right-handed.

Prebiotic chemists have long been at a loss to explain how the first living systems could have extracted just one kind of the handed chemicals from the mixtures on the early Earth. Left-handed nucleotides are a poison because they prevent right-handed nucleotides linking up in a chain to form nucleic acids like RNA or DNA. Dr. Joyce refers to the problem as “original syn,” referring to the chemist’s terms syn and anti for the structures in the handed forms.

The chemists have now been granted an unexpected absolution from their original syn problem. Researchers like Donna Blackmond of Imperial College London have discovered that a mixture of left-handed and right-handed molecules can be converted to just one form by cycles of freezing and melting.
Hmmm ... I see two problems here. First, I'm not aware of any experiments by Donna Blackmond or anyone else that solves the chirality problem. Does anyone have a reference?

The second problem with Wade's description concerns the "handedness" of nucleotides. It's true that the sugar component of nucleotides is exclusively D-ribose (or D-deoxyribose) and not L-ribose. The nucleic acids that we know today (DNA and RNA) could not be made with L-ribose or L-deoxyribose. This is a "problem" that's similar to the one with amino acids; how do you get a pool of sugars that are all D- configurations? (Do you get them by synthesizing them all from D-glyceraldehyde?)

The terms syn and anti refer to different conformations of nucleotides and not different stereoisomers. Conformations are different three-dimensional shapes that a molecule can adopt in solution. They don't require the breaking of any chemical bonds. See Nucleotides Can Adopt Many Different Conformations for a discussion of these different shapes.

Here's a figure showing the anti and syn conformations of deoxyguanylate. (Click to embiggen.)


Free nucleotides can easily switch back and forth between the two forms since all it requires is rotation around the β-N-glycosidic bond—the one with the circular arrow around it. This has nothing to do with stereochemistry or the chirality problem.

In fact, nucleotides like deoxyguanylate can switch between the two conformations even while they are part of DNA. The anti conformation is found in normal B-DNA but the double helix can adopt a Z-DNA conformation under some circumstances and in that conformation the deoxyguanylate residues are in the syn conformation.

Mistakes like this are what makes science journalism difficult. I don't expect Nicholas Wade to be an expert in biochemistry—although if he'd had a copy of my textbook he could have avoided the error. What I do expect is a bit of fact-checking with other experts. Wade could have asked any biochemist to check this out.

Furthermore, Wade should probably have been suspicious when he realized that the syn and anti conformations of nucleotides don't come up in any other discussions about chirality. Indeed, nucleotides are rarely mentioned in such discussions.


[Figure is from Moran/Scrimgeour et al. Biochemistry 2nd ed. (1994) ©Neil Patterson Publishers/Prentice Hall.

6 comments:

  1. Who knows, maybe Wade should have spent less time on his nifty metaphor and more time on accuracy.

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  2. donna blackmond's publications: http://www3.imperial.ac.uk/people/d.blackmond/publications

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  3. Postdiluvian posted a link to Donna Blackmond's publications.

    I read some of them before I posted. I couldn't find anything that shows how to convert a racemic mixture of amino acids to 100% L-forms by freezing and thawing.

    Did I miss something?

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  4. Bayesian Bouffant, FCDTuesday, June 16, 2009 3:20:00 PM

    Emergence of a Single Solid Chiral State from a Nearly Racemic Amino Acid Derivative
    Wim L. Noorduin,† Toshiko Izumi,‡ Alessia Millemaggi,§ Michel Leeman, Hugo Meekes,† Willem J. P. Van Enckevort,† Richard M. Kellogg,* Bernard Kaptein,*§ Elias Vlieg,*† and Donna G. Blackmond*‡;;;
    J. Am. Chem. Soc., 2008, 130 (4), pp 1158–1159
    DOI: 10.1021/ja7106349

    The evolution of a single chiral solid state is reported for an amino acid derivative starting from a nearly racemic mixture of solid left- and right-handed crystals. Attrition-enhanced dissolution and recrystallization processes based on solubility considerations of the Gibbs−Thomson rule, coupled with solution-phase racemization, drive this near-equilibrium system inexorably to single chirality in the solid phase.

    I suppose "dissolution and recrystallization processes based on solubility considerations" could be interpreted as freezing and thawing(?)

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  5. I am not sure Wade made the mistake you accuse him of making...

    Wade:
    Left-handed nucleotides are a poison because they prevent right-handed nucleotides linking up in a chain to form nucleic acids like RNA or DNA. Dr. Joyce refers to the problem as “original syn,” referring to the chemist’s terms syn and anti for the structures in the handed forms.

    You:
    In fact, nucleotides like deoxyguanylate can switch between the two conformations even while they are part of DNA. The anti conformation is found in normal B-DNA but the double helix can adopt a Z-DNA conformation under some circumstances and in that conformation the deoxyguanylate residues are in the syn conformation.

    Sure, Wade's sentence is unclear and confusing but it is possible that he meant what you describe: that right-handed nucleotides (D-ribose-based) in anti conformation make up right-handed DNA while in syn conformation the DNA becomes left-handed (Z-DNA)!

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  6. I've heard Prof. Blackmond lecture. The enantiomeric selection depends on, among other things, a selection effect. Early microcrystals form at random and seed the production of similarly handed crystals, leading to a separation between the soluble and crystal forms. The phenomenon has been repeated in other contexts by, e.g., David Deamer. It's pretty damn good science.

    Even better is the fun of telling a creationist who raises this old "evidence against evolution" that he's behind on the chemical literature. Hee. Hee.

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