Field of Science

Solving an unnecessary problem: chirality and the origin of life

Larry Moran has a post up about a new paper that claims to help solve the 'problem' of the origin of biological chirality by showing that amino acids forming in space are not an equal mix of the two 'mirror' isomers but slightly biased towards the L isomers used by living organisms for protein synthesis. [NON-RACEMIC AMINO ACID PRODUCTION BY ULTRAVIOLET IRRADIATION OF ACHIRAL INTERSTELLAR ICE ANALOGS WITH CIRCULARLY POLARIZED LIGHT]. I was going to write a post arguing that the use of only one isomer isn't a problem in need of explanation, but then realized that I'd written such a post several years ago.   I haven't seen my argument being made anywhere else, so I'm reposting it below.

Is the origin of biological chirality a no-brainer?

One argument invoked by creationists for a magical origin of life is that the observed homochirality (definition below) of biological molecules could not have arisen without divine intervention. Creationists are notorious for their sloppy reasoning, but I'm a bit puzzled that scientists also see this as a big problem. Here's an example from the Answers in Genesis people, and the blue box in this article is an example from PLoS Biology.

The fundamental argument seems to be that some special forces or factors are needed to explain how and/or why the first living things used only D-sugars and only L-amino acids. It's often claimed that this would not have happened unless the starting abiotic materials had an excess of one enantiomer (definition below) over the other.

I think people have fallen into the error of assuming that, at the molecular level, enantiomers are much more similar to each other than to other related molecules. But it shouldn't be any harder for an asymmetric reactant or catalyst to distinguish D-glucose from L-glucose than from either enantiomer of fructose or galactose. Or to distinguish L-leucine from D-leucine than from D- or L-isoleucine. They may contain the same atoms but they all have entirely different shapes, and so they are all entirely different molecules.

(Here's the same point made about words. The words pacer and recap are palindromes, but most readers have no more trouble telling them apart than telling either from caper.)

Chemists discovered chirality when investigating the bulk properties of pure crystals and solutions. Chemical synthesis of a chiral molecule from simpler non-chiral precursors usually produces equal amounts of both enantiomers, whose identical physical properties make them very difficult to separate. Chemists thus view enantiomers as almost-identical molecules, differing only in their 'handedness'.

But chemists are late arrivals on the evolutionary scene, and the first self-replicating entities would usually have interacted with individual molecules in complex mixtures. Because all but the simplest of biologically relevant molecules are asymmetric, most inter-molecular interactions would always have been between asymmetric participants, each no more likely to confuse their partner with its enantiomer than with any other molecule. The fact that crystals of D-glucose and L-glucose have the same bulk properties (solubility, melting temperature) would have been irrelevant.

We don't need to fuss with defining 'life', but can simply think about the origin of entities capable of evolving by natural selection (having heritable variation causing differential reproduction). Any molecule complex enough to have heritable variation would certainly have been complex enough to be asymmetric. To such molecules, discrimination between enantiomers wouldn't have been any more of a problem than discriminating between other possible reactants.

Although this now seems so obvious to me, I only realized it a couple of years ago. Until then I unquestioningly accepted the general teaching that the origin of biological chirality was a big problem. Am I missing something?

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Definitions of enantiomer and homochirality: Like letters in words, the same combinations of atoms can be put together in different arrangements. Sometimes the arrangements can be mirror-images of each other. Chemists call molecules that contain the same atoms connected in mirror-symmetry arrangements enantiomers of each other. Enantiomers are distinct molecules (like the words speed and deeps), but pure preparations of these chiral molecules have the same bulk physical properties. The molecules found in organisms are usually homochiral: only one of the two enantiomers is used. Our metabolism uses only the D enantiomers of sugars and only the L enantiomers of amino acids. 

Teaching genetics has devoured most of my brain...

... but the rest of the lab is moving ahead.

We're doing some revisions on our failed-again CIHR proposal about DNA uptake, and will pass it on to two internal reviewers on Monday.  They're both microbiologists and we hope their comments will help us fine-tune it for the Microbiology and Infectious Diseases review committee.

The RA is about to do some preliminary cross-linking experiments that we hope to add to the proposal.

The post-doc and I are making good progress on the first of his two papers (both of which we plan to submit before the March 1 CIHR deadline).  He's going to present a fairly complete version of it at today's lab meeting.

I need to spend part of today working on a draft of the Response to Reviewers (when I'm not devising beautiful teaching slides to illustrate how elegantly meiosis solves the problems of correctly segregating homologous chromosomes).

Well that was bad advice...

The grant proposal we submitted to the Canadian Institutes for Health Research (Canada's NIH) in September has scored much too low to be funded.

We were very optimistic that it would succeed.  An earlier version submitted in March had just missed the funding cutoff (it ranked #10 out of 47 but only 8 of these were funded), and the reviewers' comments on it had contained only a few relatively minor criticisms.   I had later spoken to the Chair of the review committee (Biochemistry and Molecular Biology-B) to ask whether the committee might have felt that this proposal did not really fall under their mandate and should have instead been sent to the Microbiology and Infectious Diseases committee.  He said that he had initially been concerned that this would be a problem, but that the committee had been very supportive of the project, saying that this was exactly the kind of work they should be funding.

Before this resubmission we had drafts of the proposal reviewed by three UBC faculty members.  All thought it was already very strong, but they also made many suggestions of ways to make it even better, all of which we implemented.  We posted the final proposal on the 'What we're planning' page of our lab's website, so you can download a pdf of the Summary here, and of the full proposal here.

But this time we were unlucky.  The two reviewers assigned to fully evaluate the proposal had not seen the earlier version, and although one of them was 'very enthusiastic', the other argued that the problem of how bacteria take up DNA was unimportant even within microbiology, and clearly felt that the committee should not waste its scarce resources on our work. 

So, Plan B.  The next deadline for resubmission is March 1, and we'll send a revised version to the Microbiology and Infectious Diseases committee.  I don't think we'll change much of the science in the proposal, but we will redo the parts that explain why the research is important.  In the previous version we had emphasized its significance for molecular biology.  However that seems to have backfired, as the harsh reviewer argued that the controversy about the function of DNA uptake (which we had deliberately not raised for this committee) reduced the value of the research we proposed.  For this new committee we'll emphasize the microbiology.

Because we don't have many publications in the last year or two, I think we need to get both of the post-doc's manuscripts submitted to journals before we submit the revised proposal.  One of these manuscripts is well under way, but the other is more important, as it reports the best of the preliminary work we describe in the proposal.

Writing these manuscripts, polishing the proposal, and teaching my new genetics course are going to occupy all my time for the next seven weeks, so I won't have any chance of getting back to the bench until March.

Announcing ScienceLeaks

This venture was triggered by the many people complaining that they couldn't evaluate the 'arseniclife' paper because the journal Science only allowed access to its abstract, not to the full paper or its supplementary online materials.  In response, Science temporarily opened access to people wiling to register at their site, but when the month ends the barrier will go right back up.

This access problem applies to the great majority of scientific papers.  The public pays for the research, but the results are locked behind journal-subscription paywalls, accessible only to people with personal subscriptions or affiliated with major research libraries, or to those willing to pay $20-$40 for access to individual articles.

Most researchers agree that this legacy of the pre-internet days is morally wrong and unfair to everyone.  Those of us who can afford it pay thousands of dollars to the journals to make our own articles open access.  And many of us post PDFs of our own papers on our personal web sites.  But these aren't easy to find, especially for people not working in the field.

So I've set up a web site called Science Leaks (actually a Blogger blog) to serve as a clearing house, providing links to the papers people want to read.  Anyone who's looking for access to a paper can simply post the paper's information as a comment, and anyone who knows where a pdf is available can then post the link.  (Once a link is posted I'll remove the request comment, to keep things tidy.)

This is just a stopgap solution.  In the short term, if there's sufficient interest someone will (I hope) help me to set up a better site.  But the real solution is to change from having subscribers pay publication costs to having granting agencies pay them, either directly or as a line item in grant budgets.