Forum

Why, and how did life settle on L-amino acids and D-nucleic acids? And what are the prospects for finding life of opposite "handedness" elsewhere in the universe?

  1. Aaron Burton


    Life on Earth has settled exclusively on D-nucleic acids and L-amino acids in proteins. And many enzymes only act on substrates of a specific chirality. However, lab studies have shown that both L-nucleic acid enzymes and proteins made of D-nucleic acids are catalytically active. This finding implies it was not an absolute requirement that life adopt L-amino acids and D-nucleic acids. Some questions I think are interesting are:

    1) What was the driving force behind the adoption of L-amino acids and D-sugars in nucleic acids? Was this a concerted process where both became fixed simultaneously or did one drive the other?

    2) Is a same-chirality system possible? Could you have a life system based on all L or all D amino acids and sugars? As an example, could you select for an RNA polymerase protein made entirely of D-amino acids? Would it bear any resemblance to an RNA polymerase made entirely of L-amino acids selected under the same conditions?

  2. George Cody


    Chirality is a question that appears to only be seriously relevant at the point that macromolecular catalysis becomes important. There are evidently symmetry breaking events that do not involve astrochemistry that are not at all understood or even accepted. This is an important question, but absent any underlying physical guide- solution (in my view) is going to serendipity.

  3. Ali Mallakin


    The answer may be given through quantum mechanics. I will give few hints as I had some work on quantum mechanical calculations 10-year ago in respect to Polycyclic Aromatic Hydrocarbons (PAH) molecular modeling. Basically electrostatic energies of molecules show equal energies for D and L amino acids as no chirality applied in the electrostatic energy. Calculation of “the parity-violating energy difference (PVED)” between the L- and D-amino acids show L-amino acids are stabilized with respect to D-amino acids, and D-sugars with respect to L-sugars.The parity violating energy difference (PVED) is very small number and that results in an enantiomeric excess for the L-amino acids. The PVED increases by atomic number and this allows for a small difference between different enantiomers. The small number of PVED value for organic molecules may give rise to the specific chirality of molecules found in nature today. A further possibility for the origins of chirality on Earth can be related to extraterrestrial origin. The initial seeds for molecules with homochirality may have been planted on Earth by the heavy rain of meteorites bombartment(s).

  4. George E Fox


    This is in response to George Cody’s point that “Chirality is a question that appears to only be seriously relevant at the point that macromolecular catalysis becomes important”. Modern proteins are chiral because they are made by a ribosomal protein synthesis system that is tuned for chirality. However, the system has probably not always been fully chiral. Chirality occurs in the ribosome in two places; attachment of an L-amino acid to tRNAs and the actual synthesis step at the peptidyl transferase center. In the case of tRNA charging, there are several alternative systems including in some synthetases an editing domain that remove D-amino acids if they get attached to the tRNA. Such mechanisms would be a later evolutionary development, so the first tRNAs likely were charged with both D & L amino acids. This is not a fatal problem in the modern system because the peptidyl transferase center excludes tRNAs carrying D-amino acids. However, Sidney Hecht has shown that by introducing mutations in the peptidyl transferase center region of the ribosome that it becomes possible for the machinery to accept tRNAs charged with D-amino acids and incorporate them into proteins. This basically shows that the modern system has been optimized over evolutionary time. Thus, there is no assurance that the peptides/proteins made by the early ribosomes were actually chiral. However, the fact that protein synthesis is a two step process (charging and synthesis) would result in rapid emergence of almost complete chirality if both steps had the same preference. Thus, if the world was not already chiral, the ribosome would have made it so. This of course does not address the origin of chirality of the RNAs. From a future work perspective I would argue that it is very relevant to study the properties of peptides of mixed chirality or perhaps say a 75-25 mix etc. It would be interesting to see what functions could be selected for using pools of such achiral or partially chiral mixes.

  5. Aaron David Goldman


    I agree with George Fox and would also add that chirality of amino acids is set by biosynthesis and I believe it is determined metabolically downstream by the chirality of the sugars. So in that sense the two chiralities are actually one linked to one another as a single phenomenon. Chirality is clearly important if you are, say, making your own proteins through translation of genes and expecting them to do the job they have evolved to do. But I think we need to know more about how racemic mixtures affect the frequency of getting functions in so-called “statistical proteins” scenario (essentially what George Fox wrote above). It might also be worth considering whether a primitive translation system would have been using a racemic mixture of amino acids from the environment and, if so, what effect this would have had on early life, its evolution, and perhaps the amino acid library it was using.

  6. Loren Williams


    I think you guys have touched on the main points here. But just to reiterate the intrinsic biological requirement for chirality:

    1) A racemate protein (a protein made of a racemic mix of amino acids) cannot fold. 2) A folded protein enzyme with a racemic mix of aas in the active site cannot catalyze. The same applies to RNA. So there is an overwhelming strong evolutionary driving force toward homochirality. You don’t need quantum mechanics or circularly polarized light, just evolution. But the absolution relationship between the chiralities of sugars and amino acids… that is a tougher and more subtle question.

  7. Ali Mallakin


    I second G. Fox comments but from the point of evolution and quantum mechanic, evolution itself may have been bonded to the quantum mechanical concept. Connecting the quantum mechanical principle to the evolution means to endure grope for new type of organisms. Organisms that continue to exist unlock the door to further developments on that steady foundation. Einstein’s unfinished work on space-time could be the guide to find the way through a huge range of changes within the given scope of possibilities. There are many unanswered questions and one is what actually caused the alteration. Is change an integrated characteristic of the cosmic structure, which is known as “anthropic principle” (the corporal laws of natural world that oblige the universe to develop compatible environments for life), or the change caused by external accidental impacts of rays and chemistry? Letting quantum mechanics to enter the celestial juncture of evolution puts statistics and probabilities on the table. Something far more than Darwin’s view.

  8. Sara I Walker


    I agree with the primary thread of discussion here that chiral symmetry breaking probably occurred at the macromolecular level. To take the discussion in a slightly different direction, it seems that the majority work on homochirality and the emergence of life focuses on prebiotic mechanisms for symmetry breaking (i.e. UV light, mineral surfaces, autocatalytic reactions, grinding) and there is not as large an industry in detailing how homochirality might have emerged in early evolution (present company excluded as George Fox has done excellent work in this regard). I find this interesting because we have another community of astrobiologists working in life-detection experiments that want to use homochirality as a universal biosignature. Perhaps this road mapping exercise is a good opportunity to engage these two communities to come up with ideas for experiments and models that might not only inform the origin-of-life debate but also how we look for life (e.g. if early biosystems could really get by with mixed peptides prior to refinement of the translation machinery then we may need to rethink how we use chirality as a biosignature – i.e. is there a critical threshold below 100% L or D, say 70 L/ 30 D (or vice versa) below which the system doesn’t work?).

  9. Ian James Miller


    At the risk of repeating another post, I think Loren is more or less right. For me the key is reproduction. Reproduction occurs through a duplex, and you cannot have a tightly bound duplex without constant pitch in each helix. Constant pitch means homochiral. Anything that does not reproduce is going to get swamped out by that which does, and which has the ability to “eat” unsuccessful entities. Homochirality is inevitable for life, because wihthout reproduction you do not really have life.

  10. Marc Fries


    My suspicion is that it doesn’t matter which chirality is expressed in either case, only that one is chosen. In all the biochemical machinery within these cells, it really only takes a single chemical process with a slightly faster reaction rate for the organism – and soon the entire population – to select for the more efficient process. I suspect that it doesn’t matter which chirality is actually selected, but as soon as one is in place the newly efficient organism will rapidly dominate its environmental niche. In other words, I agree with Loren’s comment that evolution will drive selection for a chiral system, and probably very early on in the process.