Chemistry Everyday for Everyone
“Biochemical Predestination” as Heuristic Principle for Understanding the Origin of Life Stephan Berry Max-Volmer Institut für Biophysikalische Chemie und Biochemie, Technische Universität Berlin Strasse des 17. Juni 135, 10623 Berlin, Germany Life as a cosmic imperative is the subtitle of de Duve’s book Vital Dust (1), and this phrase also summarizes its main statement: the origin (and further evolution) of life on Earth did not occur by chance but is a consequence of the laws of chemistry. Since these laws are valid throughout the universe, it is concluded that life is indeed a cosmic phenomenon which is not restricted to our solar system. However, de Duve is still moderate in his conclusions insofar as he considers the possibility that life on other planets might be substantially different from terrestrial life. But given a strong influence of fundamental laws on the appearance of life, it is only consistent to ask how far this influence goes and what is left for chance, which uniquely shapes life on a given planet. Stressing the role of chemical laws for prebiotic chemistry, de Duve stands not alone (2). Kenyon and Steinman (3) coined the expression “biochemical predestination” for describing the following causal chain: the properties of the chemical elements dictate the types of monomers that can be formed in prebiotic syntheses, which then dictate the properties of the occurring polymers, which finally dictate the properties of the first eobionts and all succeeding cells. Therefore, the principle of biochemical predestination does not merely mean that there was a high probability for any form of life to occur on young Earth, it means that due to strong physicochemical constraints life had to arise with quite exactly the basic biochemistry it actually has. In the strictest interpretation, the concept of biochemical predestination would mean that all major reactions being part of current biochemistry are related to a prebiotic counterpart. Such a stringent interpretation is also favored by de Duve. This would, for instance, rule out a scenario such as the genetic takeover of Cairns Smith (4), in which clay minerals instead of organic polymers are proposed as primordial genes—since in modern biochemistry there is no involvement of clays in genetics. In the same way it has been argued against the hypercycle of Eigen and Schuster (5), because today genetic information transfer is organized in a linear sequence DNA → RNA → protein rather than in a cycle (6). However, the discovery of RNA with catalytic functions (7) makes this objection pointless and strongly increases the plausibility of a hypercycle in an early RNA world. The notion of strict laws governing natural processes is common to all scientific disciplines. Studying the origin of life is a typical problem of historical reconstruction, and like any historical discipline, this area of research is ultimately not possible without the recognition of laws: reconstruction of past events from present evidence requires time-invariant laws. But both these arguments, the ubiquity of laws in nature and the heuristic requirement of laws for historical reconstruction, are of course not proving the idea of biochemical predestination. Like all scientific ideas, it has to be judged from its explanatory and predictive
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value. In any case, the biochemical predestination principle may serve as a valuable null hypothesis against which specific explanations invoking “frozen accidents“ for given features of terrestrial life can be compared. Evidence has accumulated that in fact much of the chemical design of life on Earth can be explained by physicochemical necessities. The amino acids that are predominantly formed in simulation experiments of the Miller type are also those that occur most frequently in proteins (and in cosmic matter as well). In particular, the high yield of αamino acids compared to β- and other isomers is remarkable. There are also arguments explaining the superiority of amino acids over other bifunctional monomers such as hydroxy acids, which could be envisaged as potential building blocks of biopolymers (8). Many biological molecules have systems of delocalized π-electrons, which makes sense in terms of stability under prebiotic conditions (9). Adenine, which is the most important of all biochemically relevant purine bases, has the largest resonance energy per π-electron (10) and it is also the one of the five nucleobases that is formed with highest yield in some simulation experiments. Resonance stabilization also contributes to the great stability of the porphyrins. Most probably they were important molecules from the beginning, especially as they might have accumulated by an autocatalytic prebiotic formation reaction (11). And of the four isomers of the porphyrin precursor uroporphyrinogen (12), the one designated number III is formed with the highest yield in a nonenzymatic synthesis, possibly recapitulating a prebiotic path. Not surprisingly, this uroporphyrinogen III is the one that plays a key role in porphyrin metabolism today. The biochemical predestination principle does not only explain what happened; in some cases it may also illuminate what did not happen. The enzymes of anaerobes, which may reflect an early enzyme inventory, contain several metals as cofactors (e.g., iron, molybdenum, zinc, manganese, cobalt, nickel). Copper is typically absent; and this corresponds to the fact that copper(I) sulfide, which must have been the predominant copper species in the reducing primordial ocean, is many orders of magnitude less watersoluble than the other metal sulfides (13). Early biochemistry is greatly influenced by the availability of substances, which in turn depends on physicochemical laws. The role of organohalogens in biochemistry may serve as another example. Normally this is not discussed in an origin-of-life context, but it is of value for illustrating the principle of biochemical predestination. For a long time the opinion prevailed that animate nature avoids the use of organohalogens, which were regarded as a mere curiosity, restricted in occurrence to thyroxin and a few other examples. This is wrong, and the number of known compounds rose from 30 in 1968 to some 2000 in 1994 (14). However, even despite the plethora of recently discovered biotic
Journal of Chemical Education • Vol. 74 No. 8 August 1997
Chemistry Everyday for Everyone organohalogens, it is still true that the basic biochemical functions of all organisms, namely, storage and transmission of genetic information and metabolic energy, do not make use of halogenated compounds. All biotic halogenated compounds are secondary metabolites—secondary with respect to their role in metabolism, but also, one must assume, secondary with respect to their occurrence in the course of evolution. So why are halogens absent from the basic constituents of life? It is, for instance, easy to understand why selenium did not assume a role similar to sulfur, because, besides differences in the chemistry, it is three orders of magnitude less abundant. But chlorine is not a rare element: its abundance is similar to that of sulfur, phosphorus, or nitrogen. The notion that life decided in principle against chlorinated or other halogenated compounds because of their inherent toxicity is obviously not true. Moreover, this argument is irrelevant because toxicity requires an already existing metabolism in the context of which toxic effects can occur. The high resistance of chlorinated compounds to degradation, which causes much environmental concern today, would be clearly advantageous in prebiotic times. Stability and accumulation of monomeric building blocks is a critical point in any origin-of-life scenario; see, for example, ref 15. In light of the biochemical predestination principle, one may conclude that the fundamental biochemical reactions do not involve chlorinated compounds because they where not formed abiotically in sufficient amounts. Only after sophisticated enzymatic reactions had come into existence was it possible to integrate organohalogens into biochemistry. The implication of chlorine is not usually addressed in simulation experiments on prebiotic chemistry, but the above reasoning would predict that no compounds suited as building blocks for biological material should occur. Some experiments were done in liquid phase with chloride being present (e.g., ref 16), and their results seem to be in accordance with that prediction. However, more interesting would be the investigation of gas-phase experiments of the Miller type with some chlorine added, for example in the form of HCl or chloride-containing aerosol. Finally, a problem in the application of the biochemical predestination principle to other planets should be mentioned. Planetary chemistry does not only depend on the given mixture of elements, it is also dependent on factors such as solar irradiation, pressure, and temperature. Therefore, it seems that one cannot expect life on Jupiter or Saturn, although they have a rich and complicated atmospheric chemistry based on the same group of elements (CHONSP) representing the basis for terrestrial life. But how much Earth-likeness is actually necessary for a planet to yield a promising prebiotic chemistry? This question gained additional relevance after the recent announcement of the discovery of two planets outside our solar system, which were suggested as possible candidates for alien life (17). They are thought to have surface temperatures allowing for the existence of liquid water, but since both of them were reported to be even larger than Jupiter, they will certainly not be very similar to Earth.
Acknowledgment I thank Roland Brandt for critically reading the manuscript. Note Added in Proof Since the submission of this paper there have been important developments that deserve brief mention. The number of reported planets outside our solar system has increased steadily, the current score being about 10; see http:/ /cannon.sfsu.edu/~williams/planetsearch/planetsearch. html for latest results, but see also Gray, D. F. Nature 1997, 385, 795–796. A sensation was caused by the paper by McKay et al. (Science 1996, 273, 924–930), who presented evidence for remnants of bacteria-like organisms in the Martian meteorite ALH84001. This would be the first identification of extraterrestrial life, but it seems that more work is needed to confirm these results. See Grady, Wright, and Pillinger (Nature 1996, 382, 575–576), Chyba (Nature 1996, 382, 576–577), and Kerr (Science 1996, 273, 864–866) for commentaries and discussions. Cronin and Pizzarello’s analysis of the abiotically formed amino acids in the Murchison meteorite (Science 1997, 275, 951–955) gives clear evidence for an excess of L enantiomers over D enantiomers. The authors conclude that “the results are indicative of an asymmetric influence on organic chemical evolution before the origin of life”—another example of biochemical predestination. Literature Cited 1. de Duve, C. Vital Dust; Basic Books: New York, 1995. 2. Oparin, A. I. In Exobiology; Ponnamperuma, C., Ed.; North-Holland: Amsterdam, 1972; Chapter 1. 3. Kenyon, D. H.; Steinman, G. Biochemical Predestination; McGraw-Hill: New York, 1969. 4. Cairns-Smith, A. G. Genetic Takeover and the Mineral Origins of Life; Cambridge University: Cambridge, MA, 1982. 5. Eigen, M.; Schuster, P. The Hypercycle. A Principle of Natural Selforganization; Springer: Berlin, 1979. 6. Wicken, J. S. J. Theor. Biol. 1985, 117, 545–561. 7. Cech, T. R.; Bass, B. L. Annu. Rev. Biochem. 1986, 55, 599–629. 8. Rich, A. In Chemical Evolution and the Origin of Life; Buvet, R; Ponnamperuma, C., Eds.; North-Holland: Amsterdam, 1971; pp 180–196. 9. Pullman, A.; Pullman, B. Nature 1962, 196, 1137–1142. 10. Pullman, B.; Pullman, A. Quantum Biochemistry; Interscience: New York, 1963. 11. Calvin, M. Chemical Evolution; Clarendon: Oxford, 1969. 12. Battersby, A. R.; Fookes, C. J. R.; Matcham, G. W. J.; McDonald, E. Nature 1980, 285, 17–12. 13. Chapman, D. J.; Schopf, J. W. In Earth’s Earliest Biosphere; Schopf, J. W., Ed.; Princeton University: Princeton, NJ, 1983; pp 302–320. 14. Gribble, G. W. J. Chem. Educ. 1994, 71, 907–911. 15. Larralde, R.; Robertson, M. P.; Miller, S. L. Proc. Natl. Acad. Sci. USA 1995, 92, 8158–8160. 16. Bahadur, K. Nature 1954, 173, 1141. 17. Sage, L. Nature 1996, 379, 290.
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