A case of out and out plagiarism.
Google has made it possible to search the web for anything related to key words or phrases. I sometimes use this capability to look for papers I haven’t known about already. Usually there are too many results and many are not reliable. During such a search in the area of the “origins of life” I came across the paper you can read below. I give the URL but expect that eventually the plagiarist will have it removed. However, in the mean time please take a look. After looking at and even reading this paper, please go to the bottom of the article and read my commentary (page 12 of this document). The commentary is located just above The Teacher’s File that contains the original paper.
http://www.coenzyme-a.com/origins_of_life.html
The Biochemical Functions of Coenzyme A
in THE ORIGINS OF LIFE and THE PRIMORDIAL SOUP
by Nickolaos D. Skouras PhD.
Summary
Many solar systems in the universe may be expected to contain rocky planets that have accreted organic compounds. These compounds are likely to be universally found. In addition the chemistry of sulfur, phosphorus, and iron is likely to dominate energy transductions and monomer activation, leading to the eventual emergence of polymers. Acyl carrier Proteins, Coenzyme A and polynucleotides provide all living mater with a wide variety of chemical reactions, function, structure, and information. The conceptual puzzle regarding their emergence is discussed. The fitness of various elements to serve various roles is analyzed from the viewpoint of electron orbitals. These elements with orbitals are of great importance.
The Constructionistic Approach
The study of the origin of life is a multidisciplinary undertaking involving both experimental and conceptual components. For example physics, mathematics, chemistry, cell biology, geophysics, and cosmology, they each contribute essential features of a complete picture. Consequently, most research papers or books on these subjects involve isolated particulars, one must work assiduously to provide a general synthesis within to place this information. The following material is intended to aid us in building a sufficiently rich context for such a synthesis.
At its most fundamental level, an understanding of the origin of life must have an experimental foundation. This type of procedure is called a Constructionistic approach, when truly understood we will be able to construct in the laboratory the chemical process leading to the formation of a cell. It was given its name the Constructionistic approach by its principal contemporary proponent, Sidney Fox (S. W. Fox 1988, Fox and Dose 1972).
ABSTRACTIONS
Conceptualization is the process of creating abstract ideas. Mathematics and the physical sciences are replete with this process. Several abstract ideas that are crucial for a study of the origin of life come to us from the disciplines of biochemiistry and molecuar biology (de Duve 1984; Stryer 1988; Watson 1975). They include (1) catalysis (autocatalysis), (2) allostery (flexibility of multiple weak bonds), and (3) self- assembly.
Catalysis
Many proteins in the cell are enzymes, specific catalysts of specific reactions with the ability to recognize specific substrates. Their functionality follows from their structure, in particular from their conformations, which are the result of a combination of covalent bonds, ionic bonds, hydrogen bonds, hydrophobic/hydrophilic interactions, van der Waals forces, disulfide bridges, and so on. A central phenomenon is the complementarity of interaction afforded by multiple weak bonds. This provides recognition and specificity. James Watson’s Molecular Biology of the Gene (1975) did much to make an appreciation of these ideas widespread. Watson and Francis Crick showed how multiple weak bonds, specifically hydrogen bonds, permit the transfer of genetic information during replication of deoxyribonucleic acid, or DNA, transcription of DNA into ribonucleic acid, or RNA, and translation of RNA into protein amino acid sequences.
Allostery
Binding of an effector or chemical modification (often phosphorylation the introduction of a phosphate group or dephosphorylation) can trigger a conformation change. Often, the change occurs in a part of the protein spatially removed from the site of the binding or modification. This is the essence of allostery. Many regulatory interactions involving proteins are allosteric. Sometimes a modified protein in turn modifies another, and so on, in a cascade of activations or inactivations that may endow the initial effector with a highly amplified effect.
Self-Assembly
Enzyme complexes, subcellular organelles, and membranes self- assemble from their constituents (de Duve 1984). This means that once the proteins have been translated and perhaps have also been post-translationally altered, they recognize and combine with other proteins to form specific complexes. Lipids self- assemble into vesicle membranes. These processes are often driven by the increased entropy of water molecules (R. F. Fox 1982) initially associated with the proteins or the lipids, and for this reason the term self-assembly is a bit of a m isnome~ Nevertheless, sophisticated visualization techniques see decreased entropy of the proteins, the lipids, and the assembled structures while the water molecules remain invisible, and so the observer really does think he or she is seeing self-assembly.
EVOLUTION
Evolution is a dynamical process, the interplay of amplification, variation, and selection (de Duve 1991). In this context, amplification refers to the population size of a particular type of living unit. In its simplest form, this amplification is achieved by replication of the units by division; in its most complex form, by bisexual reproduction. Replication isn’t perfect, and some variations may confer felicitous functionalities. These are selected for by the dynamics of the interaction of the individual with the environment. The central concept here is fitness. Fitness means that the interaction with the environment promotes amplification of numbers of units within the niche. Fitness may well change, even reverse, over geophysical time scales (tens of millions of years).
THE PERIODIC TABLE OF THE ELEMENTS
As a starting point, we will choose to make all the matter needed for life from electrons, protons, and neutrons. All atomic nuclei are made up of protons and neutrons (nucleons), and the number of protons determines the atomic number. The production of the atomic elements, called stellar nucleosynthesis (Fowler 1967), involves a number of nuclear reaction cycles. Protons combine and some decay to form alpha particles that contain two protons and two neutrons. An alpha particle is the atomic nucleus of helium, 4He. Alphas are especially stable combinations of nucleons. Subsequent synthesis, at great pressures and temperatures, tends to produce nuclei that are simple multiples of alphas, such as 120 (carbon), 160 (oxygen), 2ONe (neon), 24Mg (magnesium), 285i (silicon), 32S (sulfur), and 400a (calcium). Note the absence of 8Be (beryllium), which happens to be especially unstable. Reactions of these nuclei with protons, such as in the carbon-nitrogen- oxygen (ONO) cycle, produce the intermediate elemental nuclei (it should be noted that in first-generation stars, 1H (hydrogen) and 4He nuclei overwhelmingly dominate, whereas in second- generation stars, 120 acts catalytically to generate much greater amounts of heavier elemental nuclei). These processes explain the relative abundance of the elements and especially the periodic dominance of alpha multiples. In a first-generation star, this progression is dominated by elements up to 56Fe (iron), the most stable nucleus. Thus, life might be expected to be based most naturally on H, C, O, Mg, Si, 5, Ca, and Fe. Indeed, it is (except for Si), although one must not overlook the central importance of N and P (phosphorus) and of Na (sodium) and K (potassium) as ions as well. Given their positions near the beginning of the second and third periods of the periodic table, Mg and Ca are usually the ions Mg2+ and Ca2+ in aqueous, living matter.<>
Our own solar system is second generation, having accreted from the products of first-generation supernovas. The inner planets (Mercury, Venus, Earth, and Mars), Earth’s moon, and the asteroids make up 0.0006 percent of the mass of our solar system and only 0.44 percent of the mass of the planets. Volatile compounds, such as H2G (water), CH4 (methane) and NH3 (ammonia), were deposited on planet Earth by bombardments of planetesimals that formed in the outer reaches of the planetary disk (Faure 1991) early in the solar system’s evolution. These volatile compounds were blown to the cold outer reaches of our nascent solar system by a strong solar wind where they coalesced into billions of planetesimals. The less volatile matter, primarily silicate rocks, remained closer in and became the foci of accretion for the planetesimals. A reminder of this early period is the extensive cratering throughout the solar system, both on rocky planets and on the moons of the gaseous planets.
While abundance is important, fitness is just as important (
S and P are especially interesting in that P is usually most fit in an aqueous milieu as phosphoric acid, H3P04, and its ionization products, and S is most fit as either combined with O, such as in sulphuric acid, H2504, or as sulfhydryl, -SH. P, as phosphate, is virtually the sole form of P in living matter. P and 5, as well as Si, are in the third period of the periodic table, and this means that they possess unfilled d orbitals for their electrons. This feature confers on P and S especially felicitous properties for group transfer and rapid reactivity as compared to C, N, and O, whereas it simultaneously explains the lack of fitness seen in Si to serve the role served instead by C, even though both have the same valence, or degree of combining power, of 4. While about 135 times more abundant in Earth’s lithosphere than is C (Needham 1965), Si makes weaker bonds that are longer than those of C. Unfilled 3d orbitals enable nucleophilic molecules with lone pairs of electrons to easily attack Si-Si bonds. In the presence of 02, NH3, and H20, such bonds are especially labile. The corresponding C-C bonds are not. It is hard to imagine any sort of life without O2, NH3, and H2O.
The ability to form double bonds depends in part on being small enough. This is why C, N, and O are frequently found with double bonds. P and S also are found with double bonds, whereas Si is not. This is because within a period of the periodic table of the elements, the size of the atoms decreases with increasing atomic number. Si is just too big, while P is the largest atom with this capability and S is the heaviest.
The presence of unfilled 3d orbitals in P and S, and not in second-period elements such as C, N, and O, is what creates the versatile reactivity seen in them. Because they are bigger than second-period elements, their bond strengths are weaker and bond lengths are longer but not as weak or as long as with Si. Their unfilled 3d orbitals provide opportunities for intermediate states of reaction for many chemical species. Together, these special properties make them more susceptible to attack or cleavage and more able to engage in exchange reactions than C, N, and O. When studying biochemistry, the student should make note of the frequent and central occurrence of P (as phosphate) and S (often as -SH) in reactions and in structures (Stryer 1988). It is hard to miss the P in polynucleotides, in adenosine triphosphate (ATP), and in allosteric protein modifications (phosphokinases). It is also hard to miss the S in acetyl-CoA, in proteins, especially in crucial structural disulfide bridges and in iron-sulfur proteins central to energy metabolism.
C is about 104 times more abundant in the universe than is P. Compared to Si and 0, this means that C and P, as well as other elements, must be concentrated by organisms in order to provide them with the amounts they require. (While some writers on the subject emphasize the low levels of natural abundance reported above [Monod 1971], it is much more realistic to recall the size of Avogadro’s number, 6.023 1023 [the number of molecules in a mole of material], which means that for every mole of Si in the universe, there are 6 1017 atoms of P. Planet Earth contains at least 1025 moles of Si!)1
By studying the many particular properties of the different elements, we can begin to see the naturalness of many of life’s molecular features, and because of this we also see why life should be similar throughout the universe, at least at its fundamental chemical level.We see myriad organic compounds and a central importance for P, 5, and Fe.
FREE ENERGIES OF FORMATION
Free energies of formation of small molecules give us some idea about which molecules should be expected in any rocky planetary setting. Many have free energies of formation more negative than the elements from which they are formed. This includes H2O, NH3, CO2 (carbon dioxide), CH2O (formaldehyde), H25O4 (sulfuric acid) H3PO4 (phosphoric acid), amino acids, simple sugars, and a host of other biologically relevant small molecules (Calvin 1969; Fox and Dose 1972). Mineral combinations such as Ca2+HPO2- (apatite), FeO/Fe203 (magnetite), and SFe (pyrite) are additional examples. Bone contains apatite in an organic matrix; banded iron formations dating back more than 3 billion years may represent deposits created by ultraviolet excitation of Fe electrons and subsequent precipitation of iron oxides in early prebiotic chemistry (de Duve 1991), and nano-scale pyrite (troilite) crystals (common in iron meteorites) make up the active centers of several essential iron-sulfur proteins. These are examples of naturally occurring atomic combinations with low tree energies of formation and no special kinetic barriers to formation.
BIOPOLYMERS
Deoxyribonucleic acid, DNA, has been called the quintessential molecule of life because its self-replicability makes it a macromolecular substrate for evolution. However, study of the detailed mechanism of replication reveals a host of large protein complexes, most notably the DNA polymerases. Without these, DNA has no chance to replicate and clearly does not self-replicate in experiments in which DNA is simply incubated with its precursor trinucleotides. Instead, hydrolysis of the nucleotides dominates. Moreover, without an even greater number of other proteins to support metabolism, there would be neither the precursor monomers nor the necessary energy for the replica’s construction. Francois Jacob (1973) has proposed that the first level of integrated molecular behavior deserving to be called a living organism occurs with the cell. Only at the level of the cell do we find a system truly reproducing itself from small molecular precursors, from which all precursor multimers and polymers are made and from which the necessary chemical energy is generated. Ribonucleic acid (RNA) and DNA cannot do this without proteins.
THE POLYMER PHASE TRANSITION
What really sets life processes apart from other chemical processes is the transition from monomeric molecules to polymeric macromolecules (R. F. Fox 1982, 1988). The principal polymers are proteins (made from amino acid monomers), polynucleotides such as DNA and RNA (made from mononucleotides), and polysaccharides (made from simple sugars). In each case the condensation of the monomers into polymers is chemically a dehydration condensation, that is, it involves the elimination of a molecule of water between two combining molecules (Calvin 1969). This is thermodynamically inhibited by the large concentration of water in all living systems and requires the input of chemical energy to be achieved by a living cell. This energy is directly or indirectly provided by the universal currency of chemical energy adenosine triphosphate, ATP (Lipmann 1941). The monomers must be activated with phosphate groups before they can spontaneously condense into polymers. Thus, antecedent to any model of polymer evolution must be an account of the emergence of phosphate energy and monomer activation. Most probably, simple pyrophosphate sufficed very early on, and it was probably formed in prebiotic oxidation-reduction reactions involving S (as thioesters) and Fe (de Duve 1991; R. F. Fox 1982, 1988). With Fe as the absorber, ultraviolet light may well have been the primary source of the energy through photo-oxidation.
COENZYMES (MULTIMERS)
Before full-scale polymers emerged, it seems probable that a period of chemical evolution developed in which mixed oligomers ("multimers" [de Duve 1991]) were formed that contained some amino acids, some sugars, some nucleosides, and some sulfhydryl compounds (e.g., acetyl-CoA, NAD, NADP, FAD (pyridine and flavin nucleotides), and pantetheine). Today, we identify these substances as coenzymes, of which there are roughly a couple dozen kinds, pieces of which we call vitamins. These catalytic multimers are central to all of modern metabolism. The core of this metabolLsm comprises the energy-yielding pathways: glycolysis, the citric acid cycle, the pentose phosphate cycle, and the electron transport chains. The coenzymes structurally recall the early evolutionary dependence on S and P (pyrophosphate). Many enzymes are a complex of a coenzyme and a protein. The coenzyme is the true catalytic center, whereas the protein portion of the complex confers specificity for substrates and allosteric regulation. The protein may also enhance the overall catalytic rate for the coenzyme-mediated reaction, perhaps by several orders of magnitude.
THE UROBOROS PUZZLE
A sequence of stages ("worlds") of molecular evolution can be investigated. The small molecules that have negative free energies of formations form naturally in appropriate geophysical niches and can be expected throughout the universe wherever there are solar systems with some rocky planets that have accreted planetesimals containing volatile organic compounds. Therefore, the finding of amino acids on the moon and in some meteorites is not a surprise. They will surely be found on Mars as well. Electron current generated by ultraviolet light impinging on Fe, or by inorganic oxidation-reduction reactions involving 5, provides the primary source of energy, ultimately yielding thioesters and then pyrophosphate energy, the "thioester-pyrophosphate world." This last form of chemical energy is extremely fit for promotion of dehydration condensation reactions, leading at first to multimers that would otherwise be thermodynamically prohibited and therefore very improbable constituents of the geophysical world (Monod 1971). But with the thioesters and pyrophosphate energy, their occurrence becomes very likely. These multimers catalyze a variety of chemical reactions that lead to a rudimentary chemical metabolism, perhaps still prior to actual living cells (i.e., encapsulation by a membrane). Modern metabolism contains many apparent vestiges of a prior thioester- and pyrophosphate- dominated world. In this energy-driven milieu, the emergence of true polymers changes from virtually impossible to highly probable. More over, the particular catalogue of molecular species that evolves in this way should be universal.
Two classes of polymers have evolved that capture the functionality of life at the molecular level: proteins and polynucleotides. The proteins are both catalytic (with specific recognition capabilities and allosteric conformation mutability) and structural. The polynucleotides are informational, providing the coding for the amino acid sequences in the proteins as well as providing part of the apparatus for the informationally directed synthesis of the proteins. Curiously, the replication of the informational polynucleotides and the transcription of DNA into RNA, as well as the translation of the messenger RNA (mRNA) into protein, requires numerous specific proteins and special RNAs (as transfer-RNAs [tRNA] and as ribosomal-RNAs [rRNA]) to catalyze the reactions. The proteins also are needed to catalyze the metabolic pathways that provide the essential ATP energy and to provide the essential monomers from which the polymers are made. Thus, contemporary life needs proteins to make polynucleotides and needs polynucleotides to make proteins.
This sort of "chicken and egg" interdependence is referred to as the "uroboros puzzle"(R.F. Fox 1982, 1988). It poses the conceptual problem of constructing a plausible, "prebiotic," chemical scenario in which some very simple processes emerge that are capable of further evolution that could lead to the contemporary complexity of the genetic apparatus and its protein biosynthesis machinery. Such a uroboros model has been proposed by the author (R. F. Fox 1982, 1988).
The uroboros model is based on the scenario given earlier for the emergence of chemical energy and multimeric catalysts. In this system, polypeptides (i.e., very small proteins) can be expected to emerge. Their emergence should not be viewed as the creation of merely random chains of amino acids, as is so often suggested in the literature (de Duve 1991; Eigen 1971). Rather, their condensation is greatly constrained by the chemical identities of the various amino acid residues,2 and the polypeptides produced possess relatively ordered sequences (Fox and Dose 1972; S. W. Fox 1988). This is an experimentally observed fact. A highly limited number of sequences occurs when compared to the combinatorially possible random sequences. (There are 2060[l]=[l]1078 possible random sequences of 20 amino acids in a protein of 60 residues in length. This number is as large as the total number of nucleons in the universe. Some simple organisms have a mere 6,000 enzymes and structural proteins, many of which are longer than 60 residues. Clearly, life depends on an incredibly small fraction of the combinatorial possibilities. This does not mean life is impossible as a natural process [Monod 1971]; it means that the limited sequences that do naturally arise possess enough diversity of function for the evolutionary process to unfold.) These small peptides would further promote the diversification of early metabolism.
It is also possible to produce rather larger polypeptides (proteinoids) from
amino acids by dry heating (Fox and Dose 1972). If one envisages the early
Earth and considers its great variety of geophysical niches, it is not hard to
picture many types of zones in which there is daily or seasonal variation in
heat and water content. Tidal zones, volcanic shorelines,
In the uroboros model, these small polynucleotides, in the presence of pyrophosphate energy, are imagined to be able to condense activated amino acids into polypeptides with sequences determined by the polynucleotide sequence. The proposed mechanism postulates amino acyl RNA ester intermediates. This model potentially explains the origin of both coding and protein biosynthesis. The RNAs serve simultaneously as genes, messenger RNAs, and transfer RNAs. This model solves tl~e conceptual uroboros problem by providing a simple, primitive mechanism that has the capacity to evolve into the complex contemporary mechanism. This is the "RNA-polypeptide world." Nevertheless, none of the model’s key features has been demonstrated experimentally to date.
During the last fifteen years, another perspective has gained temporary popularity following Thomas Cech’s discovery of ribozymes (Cech 1 986a), RNA molecules capable of catalyzing self-excision. In laboratory settings, additional catalytic capabilities have been identified for RNA, including self-replication (Cech 1986b). This has led some researchers to the notion of an "RNA-world" for the origin of life, in which a primitive RNA molecule served both as information carrier and as catalyst. However, there are many shortcomings to this model that are becoming increasingly realized by its proponents (de Duve 1991). Firstof all, RNA molecules are thermodynamically contraindicated because of their dehydration condensate structure. Even their monomeric precursors, the ribonucleosides, are small multimers also subject to the thermodynamic dehydration barrier. Second, being a catalyst fora very special process, or for perhaps a few processes, doesn’t confer general catalytic ability on the RNA species. There is absolutely no evidence for the diverse catalytic repertoire required both for energy metabolism and for monomer synthesis. Clearly, the RNA-world emerged well along the way in the evolution of living matter, after the thioester-pyrophosphate and RNA-polypeptide worlds, and did not play any role at the start.
The USDC research lead by Dr. Stanley Miller is well known for his ‘primodial soup" experiment conducted in 1953. At that time he demonstrated that amino acids could be formed, by passing an electric current through a flask of methane. This suggested that life could have risen from materials and conditions present in early history.
It was theorized (S. Miller) that many other chemicals in addition to amino acids would have to have been present to facilitate the transition to living organisms. In particular, the presence of pantetheine could have enhanced the transitional process.
Pantetheine is the metabolic substrate, which constitutes the active part of Coenzyme-A, an essential component for protein formation. Coenzyme A is used by every known organism to assist in a wide variety of biochemical reactions and is possible that in the very earliest organisms this role was played by pantetheine alone (S. Miller).
Recently in their experiment the UCSD scientists heated a mixture of pantoyl lactone, beta-alanine, and cysteamine at 40 degrees C (105 degrees F.) All three chemicals were believed to have been present on early Earth. Among the other chemicals formed was Pantetheine. This suggests that Pantetheine could have been created in margins of evaporating pools of water in prebiotic times. The results showed that amide bonds can be formed at temperatures as low as 40 degrees C, and provide strong circumstansial support for the suggestion that Pantetheine and Coenzyme A were very important in the earlyest metabolic systems, (S. Miller).
THE MYSTERY OF THE SECOND CODE
One of the details of the uroboros puzzle involves the mystery of the second code (Eigen 1971; R. F. Fox 1982, 1988). The protein translation apparatus requires that a messenger RNA, (mRNA) be read and translated into an amino acid sequence. This is achieved by a complex process that is coordinated by ribosomes and that necessitates the intermediady of transfer RNAs, tRNAs. The tRNA’s anticodon reads the codon o~i the mRNA, and the tRNA carries the cognate amino acid. The attachment of the cognate amino acid to the tRNA with the corresponding anticodon is achieved by the action of a group of pure protein enzymes called amino-acyl-tRNA synthetases. While the transcription of the DNA genes into mRNA and the reading of the mRNA codons by the tRNA anticodons is achieved by Watson-Crick base pairing, the mechanism of attachment of the correct amino acid to the correct tRNA by the synthetases is not by base pairing and involves an as yet unknown recognition mechanism. Hence, the mystery of the second code.
Many students of the subject believe that Manfred Eigen’s hypercycle model (Eigen 1971) somehow solves this problem, but Eigen’s own account clearly states otherwise and leaves the problem open. My uroboros model addresses this problem and poses a conceptual solution that includes the suggestion that amino-acyl-tRNA synthetases have had a long evolution that now obscures their origins and also makes their contemporary mechanism obscure. The mystery of the second code
INFERRING DINOSAURS
Max Delbruck (1 978) observed that it is difficult to reconstruct the "tree of life from paleontology and comparative anatomy" because fossils provide a spotty record. Although comparative anatomy, physiology, and biochemistry are much more useful than fossils for such a reconstruction, he concludes that "no amount of study of present forms would permit us to infer dinosaurs." Nevertheless, the context presented here for the emergence of life and all of its molecular constituents has the quality of an inextricable progression. Contrary to Stephen Gould’s metaphorical assertion about replaying the "tape of life" "any replay of the tape would lead evolution down a pathway radically different from the road actually taken" (Gould 1989) nearly all of the molecular features would be reproduced. What about the organismic level?
Especially central is phosphate as the universal carrier of chemical energy in the pyrophosphate linkage. Although we haven’t emphasized it so far, Ca2+ (as well as Mg2+) is very frequently associated with phosphate compounds, where it plays a regulatory role. This is especially true in muscle function, in which the cycle of actin and myosin cross-bridge attachment and detachment is closely controlled by Ca2+ fluxes into and out of muscle tissue fibrils (de Duve 1984; Stryer 1988). The extremely favorable free energy of formation of the mineral apatite makes it clear that bone will surely be a concomitant of muscle as more and more energetic muscular organisms evolve, that is, as more and more phosphate and calcium are required. So it is not so hard to "infer" vertebrates somewhere along the way during evolution (following worms with, first, calcium carbonate and, later, calcium phosphate shells, i.e., mollusks). Remembering that teeth are largely made of apatite as well, we easily infer an emphasis on teeth. Perhaps it is not so hard "to infer dinosaurs" after all at the end of an evolutionary sequence emphasizing muscle, bone, and teeth and including predatory fish, amphibians, and reptiles.
THE "FEROCITY OF CA AND P"
If we take seriously the suggestion in the previous section that the inextricable progression of life will naturally lead to something like dinosaurs, what we are doing is saying that these organisms are merely an evolutionary manifestation of the way certain particular elements manifest themselves in living tissue, for example, phosphorus and calcium. One might go further and argue that this manifestation as dinosaurs reflects the potential "ferocity of Ca and P." It is presaged by predatory fish, amphibians, and reptiles. This view is not lessened by contemplation of the more recent mammalian predators instead. Watching a videotape of a lion making a kill we clearly see the ferocity of muscle and bone and tooth.
In this regard, it is sobering to consider the evolving role of silicon. As mentioned earlier, Si is not fit for an essential biological role. While Si is more abundant than C, C is nevertheless far more suited as a constituent of living molecular matter. We do find Si in the very sharp spines of some cacti and in several other plants where it serves to strengthen stems and leaves and perhaps to inhibit herbivores by wearing down their teeth as they eat these gritty plants. With the advent of humans, evolution has taken a new direction because of the enormous human impact on the environment. Recently, Si (along with Cu [copper], which has had several earlier impacts, e.g., the bronze age and the electrified twentieth century) has entered this evolutionary process in a dramatic new way through micro-electronics, computers, and the Internet. While we cannot neglect the multifarious benefits of glass (silicates) and the wonderous contributions of computers, it is not obvious that this new role for Si (and Cu) will not, instead, add to the ferocity of Ca and P.
NOTES
1 .Mole: That amount of a given substance or species having a mass in grams numerically the same as its molecular or atomic weight; now defined equivalently in the International System of Units as the quantity of specified elementary entities (molecules, ions, electrons, or the like) that in number equals the number of atoms in 0.012 kilograms of carbon 12 (A Supplement to the Oxford English Dictionary, ed. R. W. Burchfield, [Oxford: Oxford University Press, 1976], s.v. Mole).
2.AII proteins are made up of twenty different building blocks known as amino acids, combined linearly in various ways. Each amino acid contains a residue, or group, that gives it its identity.
REFERENCES
Calvin, M.<~>1969.<~><~>Chemical Evolution.
Cech, T. R. 1986a. "RNA as an enzyme." Scientific American 255: 64
75<>
_____ 1986b. "A Model for the RNA-Catalyzed Replication of RNA."
Proceedings of the National Academy of Sciences 83: 4360 4363<>
de Duve, C. 1984. A Guided Tour of the Living Cell.
_____ 1991. Blueprint for a Cell.
Delbruck, M. 1978. "Mind from Matter?" In The Nature of Life, ed. W.
H. Heidcamp.
Eigen, M. 1971. "Self-organization and the Evolution of Biological
Macromolecules." Naturwissenschaften 58: 465 523.<>
Faure, G. 1991. Inorganic Geochemistry.
Fowler, W. A. 1967. Nuclear Astrophysics.
Fox, R. F. 1982. Biological Energy Transduction: The Uroboros.
_____ 1988. Energy and the Evolution of Life.
Fox, S. W. 1988. The Emergence of Life.
Fox, S. W., and K. Dose. 1972. Molecular Evolution and the Origin of Life.
Gould, S. J. 1989. Wonderful Life.
Jacob, F. 1973. The Logic of Life.
Monod, J. 1971. Chance and Necessity.
Pergamon Press.<>
Stryer, L. 1988. Biochemistry.
Wald, G. 1962. "Life in the Second and Third Periods; or Why Phosphorus
and Sulfur for High-Energy Bonds?" In Horizons in Biochemistry, ed. M.
Kasha and B.
Watson, J. D. 1975. Molecular Biology of the Gene. 3d ed.
Copyright © 2001-2007 Coenzyme-A Technologies Inc.TM All rights reserved.
Commentary
Note the copyright just above. This paper was written by me under the title:
"The Origins of Life:
What One Needs to Know", R. F. Fox, Zygon: Journal of Religion and Science 32,
No. 3, 393-406 (1997) and is also copyrighted.
This was an invited paper. First a disclaimer: Zygon is a journal that
tries to reconcile science and religion. I do not believe that that is possible
and that will be the topic of writing I will do later and place in the fefox.com
site. I wrote the paper because I feel that the religious perspective can
benefit from a clear statement from the scientific side. Just because I don’t
hold to religious views doesn’t mean I won’t engage in dialog with those who
do. Hence the paper. Second a reaction: It has been said that “imitation is the
sincerest form of flattery.” (Coined by Charles Caleb
Colton in 1820 in his “Lacon”, volume
I, no. 183)
Perhaps my reaction is too kind and I
should confront Mr. Skouras rather than feel flattered. However, as it
currently stands, this is a beautiful example of out and out plagiarism for all
to see. By the way, you may actually learn something from the paper too. I recommend
the version copied directly from Zygon that is below. See if you can find the
differences between the two versions.
The Teachers. File
THE
ORIGINS OF LIFE: WHAT ONE NEEDS
TO
KNOW
by
Ronald F. Fox
Abstract. Many solar systems in the universe may be expected
to contain rocky planets that have accreted organic
compounds.
These compounds are likely to be universally found. In
addition,
the chemistry of sulfur, phosphorus, and iron is likely to
dominate
energy transductions and monomer activation, leading to the
eventual emergence of polymers. Proteins and polynucleotides
provide living matter with function, structure, and
information.
The conceptual puzzle regarding their emergence is
discussed.
The fitness of various elements to serve various roles is
analyzed
from the viewpoint of electron orbitals. Elements with d
orbitals
are of central importance.
Keywords:
d orbitals;
energy metabolism; evolution; fitness; periodic
table of the elements; phosphates; phosphorus; polymers;
polynucleotides; proteins; silicon; stellar nucleosynthesis;
thioesters;
uroboros.
CONSTRUCTIONISTIC APPROACH TO THE ORIGINS OF LIFE
The study of the origin of life is a multidisciplinary
undertaking involving
both experimental and conceptual components. For example,
physics,
mathematics, chemistry, cell biology, geophysics, and
cosmology
each contribute essential features of a complete picture.
Consequently,
most research papers or books on these subjects involve
isolated particulars,
and the student must work assiduously to provide a general
synthesis
within which to place this information. The following material
is
intended to aid the student in building a sufficiently rich
context for
such a synthesis.
393
Ronald
F. Fox is Regents’ Professor of Physics at Georgia Institute of Technology in
Atlanta,
GA30332.
Permission is hereby granted to reproduce this article for class use, with this
note:
“Reprinted from Zygon: Journal of Religion and Science.
All rights reserved.”
[Zygon,
vol. 32, no. 3 (September 1997).]
©
1997 by the Joint Publication Board of Zygon.
ISSN 0591-2385
At its most fundamental level, an understanding of the
origin of life
must have an experimental foundation. When truly understood,
humankind
will be able to reconstruct in the laboratory the chemical
processes
leading to the formation of a cell. Such an approach is
called a constructionistic
approach by its principal contemporary proponent, Sidney Fox
(S. W. Fox 1988; Fox and Dose 1972). In addition, such
understanding
will require conceptual constructs that enable widespread
communicability.
This presentation will focus on the conceptual side of the
story.
ABSTRACTIONS
Conceptualization is the process of creating abstract ideas.
Mathematics
and the physical sciences are replete with this process.
Several abstract
ideas that are crucial for a study of the origin of life
come to us from the
disciplines of biochemistry and molecular biology (de Duve
1984;
Stryer 1988; Watson 1975). They include (1) catalysis
(autocatalysis),
(2) allostery (flexibility of multiple weak bonds), and (3)
self-assembly.
Catalysis. Many proteins in the cell are enzymes, specific catalysts
of specific reactions with the ability to recognize specific
substrates. Their
functionality follows from their structure, in particular
from their conformations,
which are the result of a combination of covalent bonds,
ionic
bonds, hydrogen bonds, hydrophobic/hydrophilic interactions,
van der
Waals forces, disulfide bridges, and so on. A central
phenomenon is the
complementarity of interaction afforded by multiple weak
bonds. This
provides recognition and specificity. James Watson’s Molecular
Biology of
the
Gene (1975) did much to make an appreciation
of these ideas widespread.
Watson and Francis Crick showed how multiple weak bonds,
specifically
hydrogen bonds, permit the transfer of genetic information
during replication of deoxyribonucleic acid, or DNA,
transcription of
DNA into ribonucleic acid, or RNA, and translation of RNA
into protein
amino acid sequences.
Allostery. Binding of an effector or chemical modification (often
phosphorylation—the introduction of a phosphate group—or dephosphorylation)
can trigger a conformation change. Often, the change
occurs in a part of the protein spatially removed from the
site of the
binding or modification. This is the essence of allostery.
Many regulatory
interactions involving proteins are allosteric. Sometimes a
modified protein
in turn modifies another, and so on, in a cascade of
activations or
inactivations that may endow the initial effector with a
highly amplified
effect.
Self-Assembly. Enzyme complexes, subcellular organelles, and
membranes self-assemble from their constituents (de Duve
1984). This
394 Zygon
means that once the proteins have been translated and
perhaps have also
been post-translationally altered, they recognize and
combine with other
proteins to form specific complexes. Lipids self-assemble
into vesicle
membranes. These processes are often driven by the increased
entropy of
water molecules (R. F. Fox 1982) initially associated with
the proteins or
the lipids, and for this reason the term self-assembly
is a bit of a misnomer.
Nevertheless, sophisticated visualization techniques see
decreased
entropy of the proteins, the lipids, and the assembled
structures while the
water molecules remain invisible, and so the observer really
does think he
or she is seeing self-assembly.
EVOLUTION
Evolution is a dynamical process, the interplay of
amplification, variation,
and selection (de Duve 1991). In this context, amplification
refers
to the population size of a particular type of living unit.
In its simplest
form, this amplification is achieved by replication of the
units by division;
in its most complex form, by bisexual reproduction.
Replication
isn’t perfect, and some variations may confer felicitous
functionalities.
These are selected for by the dynamics of the interaction of
the individual
with the environment. The central concept here is fitness.
Fitness
means that the interaction with the environment promotes
amplification
of numbers of units within the niche. Fitness may well
change,
even reverse, over geophysical time scales (tens of millions
of years).
THE PERIODIC
TABLE OF THE ELEMENTS
As a starting point, we will choose to make all the matter
needed for life
from electrons, protons, and neutrons. All atomic nuclei are
made up of
protons and neutrons (nucleons), and the number of protons
determines
the atomic number. The production of the atomic elements,
called stellar
nucleosynthesis (Fowler 1967), involves a number of nuclear
reaction
cycles. Protons combine and some decay to form alpha
particles that contain
two protons and two neutrons. An alpha particle is the
atomic
nucleus of helium, 4He. Alphas are especially stable combinations of
nucleons. Subsequent synthesis, at great pressures and
temperatures, tends
to produce nuclei that are simple multiples of alphas, such
as 12C
(carbon),
16O (oxygen), 20Ne (neon), 24Mg (magnesium), 28Si (silicon), 32S (sulfur),
and 40Ca
(calcium). Note the absence of 8Be (beryllium), which happens to
be especially unstable. Reactions of these nuclei with
protons, such as in
the carbon-nitrogen-oxygen (CNO) cycle, produce the
intermediate elemental
nuclei (it should be noted that in first-generation stars, 1H (hydrogen)
and 4He nuclei
overwhelmingly dominate, whereas in secondgeneration
stars, 12C acts
catalytically to generate much greater amounts of
Ronald
F. Fox 395
heavier elemental nuclei). These processes explain the
relative abundance
of the elements and especially the periodic dominance of
alpha multiples.
In a first-generation star, this progression is dominated by
elements up to
56Fe (iron), the most stable nucleus. Thus, life might be
expected to be
based most naturally on H, C, O, Mg, Si, S, Ca, and Fe.
Indeed, it is
(except for Si), although one must not overlook the central
importance of
N and P (phosphorus) and of Na (sodium) and K (potassium) as
ions as
well. Given their positions near the beginning of the second
and third
periods of the periodic table, Mg and Ca are usually the
ions Mg2+ and
Ca2+ in
aqueous, living matter.
Our own solar system is second generation, having accreted
from the
products of first-generation supernovas. The inner planets
(Mercury,
Venus, Earth, and Mars), Earth’s moon, and the asteroids
make up
0.0006 percent of the mass of our solar system and only 0.44
percent of
the mass of the planets. Volatile compounds, such as H2O (water), CH4
(methane) and NH3 (ammonia), were deposited on planet Earth by bombardments
of planetesimals that formed in the outer reaches of the
planetary
disk (Faure 1991) early in the solar system’s evolution.
These volatile
compounds were blown to the cold outer reaches of our
nascent solar system
by a strong solar wind where they coalesced into billions of
planetesimals.
The less volatile matter, primarily silicate rocks, remained
closer in
and became the foci of accretion for the planetesimals. A
reminder of this
early period is the extensive cratering throughout the solar
system, both
on rocky planets and on the moons of the gaseous planets.
While abundance is important, fitness is just as important
(Needham
1965). By weight, three quarters of the Earth’s crust is
made of O (50
percent) and Si (25 percent), primarily as silicates. The
oceans are mostly
O (85 percent) and H (11 percent). George Wald (1962) has
explained
why Si, although the second-most-abundant terrestrial
element, is highly
unfit for living matter and indeed readily combines with O2
to make silicates,
for which it is much more fit. By examining the electronic
structures
of the elements it is also possible to understand why C, N,
and O,
along with S and P to a lesser degree, are suited to making
complex molecules
with both single and double covalent bonds. The relative
smallness
of the atoms C, N, and O enables them to make strong bonds
with short
bond lengths. As the atomic number increases, size increases
with each
period of the periodic table, and internal electron
repulsion of greater
numbers of electrons per atom also increases. Once the third
period is
finished, with the possible exceptions of selenium (Se) and
bromine (Br)
in the fourth period, all heavier atoms are typically
incapable of overcoming
these inhibitions to making multiple bonds. An interesting
wrinkle to
this view is that within a given period, the atomic size
decreases as electrons
fill up the electronic orbitals. Thus Si is bigger than P,
which is big-
396 Zygon
ger than S. The bonds are correspondingly shorter and
stronger in P and
S than in Si. Thus, it is to be expected as natural that
many solar systems
throughout the universe will contain some interior, rocky
planets, primarily
made of silicates, containing lesser amounts of a huge
variety of
molecules, primarily made of H, C, N, O, P, and S (Calvin
1969).
S and P are especially interesting in that P is usually most
fit in an
aqueous milieu as phosphoric acid, H3PO4, and its
ionization products,
and S is most fit as either combined with O, such as in
sulphuric acid,
H2SO4, or as sulfhydryl, -SH. P, as phosphate, is virtually the
sole form of
P in living matter. P and S, as well as Si, are in the third
period of the
periodic table, and this means that they possess unfilled d
orbitals for
their electrons. This feature confers on P and S especially
felicitous properties
for group transfer and rapid reactivity as compared to C, N,
and O,
whereas it simultaneously explains the lack of fitness seen
in Si to serve
the role served instead by C, even though both have the same
valence, or
degree of combining power, of 4. While about 135 times more
abundant
in Earth’s lithosphere than is C (Needham 1965), Si makes
weaker bonds
that are longer than those of C. Unfilled 3d
orbitals enable nucleophilic
molecules with lone pairs of electrons to easily attack
Si-Si bonds. In the
presence of O2, NH3, and H2O, such bonds are especially labile. The corresponding
C-C bonds are not. It is hard to imagine any sort of life
without
O2, NH3, and H2O.
The ability to form double bonds depends in part on being
small
enough. This is why C, N, and O are frequently found with
double
bonds. P and S also are found with double bonds, whereas Si
is not. This
is because within a period of the periodic table of the
elements, the size
of the atoms decreases with increasing atomic number. Si is
just too big,
while P is the largest atom with this capability and S is
the heaviest.
The presence of unfilled 3d orbitals in P and S, and not in secondperiod
elements such as C, N, and O, is what creates the versatile
reactivity
seen in them. Because they are bigger than second-period
elements,
their bond strengths are weaker and bond lengths are longer
but not as
weak or as long as with Si. Their unfilled 3d
orbitals provide opportunities
for intermediate states of reaction for many chemical
species. Together,
these special properties make them more susceptible to
attack or cleavage
and more able to engage in exchange reactions than C, N, and
O. When
studying biochemistry, the student should make note of the
frequent and
central occurrence of P (as phosphate) and S (often as -SH)
in reactions
and in structures (Stryer 1988). It is hard to miss the P in
polynucleotides,
in adenosine triphosphate (ATP), and in allosteric protein
modifications
(phosphokinases). It is also hard to miss the S in
acetyl-CoA, in proteins,
especially in crucial structural disulfide bridges and in
iron-sulfur proteins
central to energy metabolism.
Ronald
F. Fox 397
C is about 104 times more abundant in the universe than is P. Compared
to Si and O, this means that C and P, as well as other
elements,
must be concentrated by organisms in order to provide them
with the
amounts they require. (While some writers on the subject
emphasize the
low levels of natural abundance reported above [Monod 1971],
it is
much more realistic to recall the size of Avogadro’s number,
6.023 ´ 1023
[the number of molecules in a mole of material], which means
that for
every mole of Si in the universe, there are 6 ´ 1017 atoms of
P. Planet
Earth contains at least 1025 moles of Si!)1
By studying the many particular properties of the different
elements,
we can begin to see the naturalness of many of life’s
molecular features,
and because of this we also see why life should be similar
throughout the
universe, at least at its fundamental chemical level.We see
myriad organic
compounds and a central importance for P, S, and Fe.
FREE ENERGIES
OF FORMATION
Free energies of formation of small molecules give us some idea
about
which molecules should be expected in any rocky planetary
setting.
Many have free energies of formation more negative than the
elements
from which they are formed. This includes H2O, NH3, CO2
(carbon
dioxide), CH2O (formaldehyde), H2SO4 (sulfuric
acid) H3PO4
(phosphoric
acid), amino acids, simple sugars, and a host of other
biologically
relevant small molecules (Calvin 1969; Fox and Dose 1972).
Mineral
combinations such as Ca2+HPO2- (apatite),
FeO/Fe2O3
(magnetite), and
SFe (pyrite) are additional examples. Bone contains apatite
in an organic
matrix; banded iron formations dating back more than 3
billion years
may represent deposits created by ultraviolet excitation of
Fe electrons
and subsequent precipitation of iron oxides in early
prebiotic chemistry
(de Duve 1991), and nano-scale pyrite (troilite) crystals
(common in
iron meteorites) make up the active centers of several
essential ironsulfur
proteins. These are examples of naturally occurring atomic
combinations
with low free energies of formation and no special kinetic
barriers
to formation.
BIOPOLYMERS
Deoxyribonucleic acid, DNA, has been called the
quintessential molecule
of life because its self-replicability makes it a
macromolecular substrate
for evolution. However, study of the detailed mechanism of
replication reveals a host of large protein complexes, most
notably the
DNA polymerases. Without these, DNA has no chance to
replicate and
clearly does not self-replicate in experiments in which DNA
is simply
incubated with its precursor trinucleotides. Instead,
hydrolysis of the
398 Zygon
nucleotides dominates. Moreover, without an even greater
number of
other proteins to support metabolism, there would be neither
the precursor
monomers nor the necessary energy for the replica’s
construction.
Francois Jacob (1973) has proposed that the first level of
integrated
molecular behavior deserving to be called a living organism
occurs with
the cell. Only at the level of the cell do we find a system
truly reproducing
itself from small molecular precursors, from which all
precursor
multimers and polymers are made and from which the necessary
chemical
energy is generated. Ribonucleic acid (RNA) and DNA cannot
do
this without proteins.
THE POLYMER
PHASE TRANSITION
What really sets life processes apart from other chemical
processes is the
transition from monomeric molecules to polymeric
macromolecules (R.
F. Fox 1982, 1988). The principal polymers are proteins
(made from
amino acid monomers), polynucleotides such as DNA and RNA
(made
from mononucleotides), and polysaccharides (made from simple
sugars).
In each case the condensation of the monomers into polymers
is
chemically a dehydration condensation, that is, it involves
the elimination
of a molecule of water between two combining molecules
(Calvin
1969). This is thermodynamically inhibited by the large
concentration
of water in all living systems and requires the input of
chemical energy
to be achieved by a living cell. This energy is directly or
indirectly provided
by the universal currency of chemical energy adenosine
triphosphate,
ATP (Lipmann 1941). The monomers must be activated with
phosphate groups before they can spontaneously condense into
polymers.
Thus, antecedent to any model of polymer evolution must be
an
account of the emergence of phosphate energy and monomer
activation.
Most probably, simple pyrophosphate sufficed very early on,
and it was
probably formed in prebiotic oxidation-reduction reactions
involving S
(as thioesters) and Fe (de Duve 1991; R. F. Fox 1982, 1988).
With Fe as
the absorber, ultraviolet light may well have been the
primary source of
the energy through photo-oxidation.
COENZYMES (MULTIMERS)
Before full-scale polymers emerged, it seems probable that a
period of
chemical evolution developed in which mixed oligomers
(“multimers”
[de Duve 1991]) were formed that contained some amino acids,
some
sugars, some nucleosides, and some sulfhydryl compounds
(e.g., acetyl-
CoA, NAD, NADP, FAD (pyridine and flavin nucleotides), and
pantetheine).
Today, we identify these substances as coenzymes, of which
there are roughly a couple dozen kinds, pieces of which we
call vitamins.
Ronald
F. Fox 399
These catalytic multimers are central to all of modern
metabolism. The
core of this metabolism comprises the energy-yielding
pathways: glycolysis,
the citric acid cycle, the pentose phosphate cycle, and the
electron
transport chains. The coenzymes structurally recall the
early evolutionary
dependence on S and P (pyrophosphate). Many enzymes are a
complex
of a coenzyme and a protein. The coenzyme is the true
catalytic
center, whereas the protein portion of the complex confers
specificity
for substrates and allosteric regulation. The protein may
also enhance
the overall catalytic rate for the coenzyme-mediated
reaction, perhaps by
several orders of magnitude.
THE UROBOROS
PUZZLE
A sequence of stages (“worlds”) of molecular evolution can
be envisaged.
The small molecules that have negative free energies of
formations form
naturally in appropriate geophysical niches and can be
expected
throughout the universe wherever there are solar systems
with some
rocky planets that have accreted planetesimals containing
volatile
organic compounds. Therefore, the finding of amino acids on
the moon
and in some meteorites is not a surprise. They will surely
be found on
Mars as well. Electron current generated by ultraviolet
light impinging
on Fe, or by inorganic oxidation-reduction reactions
involving S, provides
the primary source of energy, ultimately yielding thioesters
and
then pyrophosphate energy, the “thioester-pyrophosphate
world.” This
last form of chemical energy is extremely fit for promotion
of dehydration
condensation reactions, leading at first to multimers that
would
otherwise be thermodynamically prohibited and therefore very
improbable
constituents of the geophysical world (Monod 1971). But with
the
thioesters and pyrophosphate energy, their occurrence
becomes very
likely. These multimers catalyze a variety of chemical
reactions that lead
to a rudimentary chemical metabolism, perhaps still prior to
actual living
cells (i.e., encapsulation by a membrane). Modern metabolism
contains
many apparent vestiges of a prior thioester- and
pyrophosphatedominated
world. In this energy-driven milieu, the emergence of true
polymers changes from virtually impossible to highly
probable. Moreover,
the particular catalogue of molecular species that evolves
in this
way should be universal.
Two classes of polymers have evolved that capture the
functionality of
life at the molecular level: proteins and polynucleotides.
The proteins are
both catalytic (with specific recognition capabilities and
allosteric conformation
mutability) and structural. The polynucleotides are
informational,
providing the coding for the amino acid sequences in the
proteins
as well as providing part of the apparatus for the
informationally directed
synthesis of the proteins. Curiously, the replication of the
informational
400 Zygon
polynucleotides and the transcription of DNA into RNA, as
well as the
translation of the messenger RNA (mRNA) into protein, requires
numerous
specific proteins and special RNAs (as transfer-RNAs [tRNA]
and as
ribosomal-RNAs [rRNA]) to catalyze the reactions. The
proteins also are
needed to catalyze the metabolic pathways that provide the
essential ATP
energy and to provide the essential monomers from which the
polymers
are made. Thus, contemporary life needs proteins to make
polynucleotides
and needs polynucleotides to make proteins.
This sort of “chicken and egg” interdependence is referred
to as the
“uroboros puzzle”(R. F. Fox 1982, 1988). It poses the
conceptual problem
of constructing a plausible, “prebiotic,” chemical scenario
in which
some very simple processes emerge that are capable of
further evolution
that could lead to the contemporary complexity of the
genetic apparatus
and its protein biosynthesis machinery. Such a uroboros
model has been
proposed by the author (R. F. Fox 1982, 1988).
The uroboros model is based on the scenario given earlier
for the
emergence of chemical energy and multimeric catalysts. In
this system,
polypeptides (i.e., very small proteins) can be expected to
emerge. Their
emergence should not be viewed as the creation of merely
random chains
of amino acids, as is so often suggested in the literature
(de Duve 1991;
Eigen 1971). Rather, their condensation is greatly
constrained by the
chemical identities of the various amino acid residues,2
and the polypeptides
produced possess relatively ordered sequences (Fox and Dose
1972;
S. W. Fox 1988). This is an experimentally observed fact. A
highly limited
number of sequences occurs when compared to the
combinatorially
possible random sequences. (There are 2060
= 1078 possible
random
sequences of 20 amino acids in a protein of 60 residues in
length. This
number is as large as the total number of nucleons in the universe.
Some
simple organisms have a mere 6,000 enzymes and structural
proteins,
many of which are longer than 60 residues. Clearly, life
depends on an
incredibly small fraction of the combinatorial
possibilities. This does not
mean life is impossible as a natural process [Monod 1971];
it means that
the limited sequences that do naturally arise possess enough
diversity of
function for the evolutionary process to unfold.) These
small peptides
would further promote the diversification of early
metabolism.
It is also possible to produce rather larger polypeptides
(proteinoids)
from amino acids by dry heating (Fox and Dose 1972). If one
envisages
the early Earth and considers its great variety of
geophysical niches, it is
not hard to picture many types of zones in which there is
daily or seasonal
variation in heat and water content. Tidal zones, volcanic
shorelines, hot
springs, and areas experiencing periodic rains are examples.
In such zones,
during the dry periods, which can be quite hot if volcanism
or even simple
baking in the hot sun is considered, the spontaneous
condensation of
Ronald
F. Fox 401
monomers into multimers and polymers takes place without
input of
chemical energy. The byproduct and inhibitor of
condensation, water, is
driven off by the heat. In the laboratory, all sorts of
biologically relevant
molecules have been synthesized in this way (Calvin 1969;
Fox and Dose
1972). When the water returns, the polypeptide constituents
created by
the dry heating spontaneously self-assemble into spherical cells
of micron
dimension. This is a very robust process, and it produces
many billions of
cellular units from milligrams of material (S. W. Fox 1988).
This is the
“proteinoid-microsphere world.” The stage is now set for the
emergence of
energy-driven vesicular micro-environments in which
conditions are ripe
for the emergence of small polynucleotides.
In the uroboros model, these small polynucleotides, in the
presence of
pyrophosphate energy, are imagined to be able to condense
activated
amino acids into polypeptides with sequences determined by
the polynucleotide
sequence. The proposed mechanism postulates amino acyl RNA
ester intermediates. This model potentially explains the
origin of both
coding and protein biosynthesis. The RNAs serve
simultaneously as
genes, messenger RNAs, and transfer RNAs. This model solves
the conceptual
uroboros problem by providing a simple, primitive mechanism
that has the capacity to evolve into the complex
contemporary mechanism.
This is the “RNA-polypeptide world.” Nevertheless, none of
the
model’s key features has been demonstrated experimentally to
date.
During the last fifteen years, another perspective has
gained temporary
popularity following Thomas Cech’s discovery of ribozymes
(Cech
1986a), RNA molecules capable of catalyzing self-excision.
In laboratory
settings, additional catalytic capabilities have been
identified for RNA,
including self-replication (Cech 1986b). This has led some
researchers to
the notion of an “RNA-world” for the origin of life, in
which a primitive
RNA molecule served both as information carrier and as
catalyst. However,
there are many shortcomings to this model that are becoming
increasingly realized by its proponents (de Duve 1991).
First of all, RNA
molecules are thermodynamically contraindicated because of
their dehydration
condensate structure. Even their monomeric precursors, the
ribonucleosides,
are small multimers also subject to the thermodynamic
dehydration barrier. Second, being a catalyst for a very
special process, or
for perhaps a few processes, doesn’t confer general
catalytic ability on the
RNA species. There is absolutely no evidence for the diverse
catalytic
repertoire required both for energy metabolism and for
monomer synthesis.
Clearly, the RNA-world emerged well along the way in the
evolution
of living matter, after the thioester-pyrophosphate and
RNA-polypeptide
worlds, and did not play any role at the start.
I described my uroboros model as a colloquium presentation
at Rockefeller
University on 28 March 1973. The following year, on 8
February, at
402 Zygon
Larry Gold’s invitation I presented the model at the Charles
Yegian
memorial symposium at the University of Colorado in Boulder.
At the
first talk, when I described how an RNA molecule could serve
both as an
information carrier and as the template for direct synthesis
of polypeptides,
I was asked by a member of the audience if I was suggesting
that
RNA was acting as a catalyst. I answered yes. I believe
someone in the
audience already used the word ribozyme
at that time. The catalytic activity
for RNA I was postulating was not the self-excision activity
found by
Cech, but it is not excluded chemically that the postulated
activity is possible
and will one day be demonstrated in the laboratory.
THE MYSTERY
OF THE SECOND CODE
One of the details of the uroboros puzzle involves the
mystery of the
second code (Eigen 1971; R. F. Fox 1982, 1988). The protein
translation
apparatus requires that a messenger RNA, (mRNA) be read and
translated into an amino acid sequence. This is achieved by
a complex
process that is coordinated by ribosomes and that
necessitates the
intermediacy of transfer RNAs, tRNAs. The tRNA’s anticodon
reads
the codon on the mRNA, and the tRNA carries the cognate
amino
acid. The attachment of the cognate amino acid to the tRNA
with the
corresponding anticodon is achieved by the action of a group
of pure
protein enzymes called amino-acyl-tRNA synthetases. While
the transcription
of the DNA genes into mRNA and the reading of the mRNA
codons by the tRNA anticodons is achieved by Watson-Crick
base
pairing, the mechanism of attachment of the correct amino
acid to the
correct tRNA by the synthetases is not by base pairing and
involves an
as yet unknown recognition mechanism. Hence, the mystery of
the
second code.
Many students of the subject believe that Manfred Eigen’s
hypercycle
model (Eigen 1971) somehow solves this problem, but Eigen’s
own
account clearly states otherwise and leaves the problem
open. My
uroboros model addresses this problem and poses a conceptual
solution
that includes the suggestion that amino-acyl-tRNA
synthetases have had
a long evolution that now obscures their origins and also
makes their
contemporary mechanism obscure. The mystery of the second
code
remains the outstanding unexplained chapter in the protein
translation
story for all contemporary organisms.
INFERRING DINOSAURS
Max Delbruck (1978) observed that it is difficult to
reconstruct the
“tree of life from paleontology and comparative anatomy”
because fossils
provide a spotty record. Although comparative anatomy,
physiology,
Ronald
F. Fox 403
and biochemistry are much more useful than fossils for such
a reconstruction,
he concludes that “no amount of study of present forms
would permit us to infer dinosaurs.” Nevertheless, the
context presented
here for the emergence of life and all of its molecular
constituents has
the quality of an inextricable progression. Contrary to
Stephen Gould’s
metaphorical assertion about replaying the “tape of
life”—“any replay of
the tape would lead evolution down a pathway radically
different from
the road actually taken” (Gould 1989)—nearly all of the
molecular features
would be reproduced. What about the organismic level?
Especially central is phosphate as the universal carrier of
chemical
energy in the pyrophosphate linkage. Although we haven’t
emphasized it
so far, Ca2+ ( as well as Mg2+) is very frequently associated with phosphate
compounds, where it plays a regulatory role. This is
especially true in
muscle function, in which the cycle of actin and myosin
cross-bridge
attachment and detachment is closely controlled by Ca2+
fluxes into and
out of muscle tissue fibrils (de Duve 1984; Stryer 1988).
The extremely
favorable free energy of formation of the mineral apatite
makes it clear
that bone will surely be a concomitant of muscle as more and
more energetic
muscular organisms evolve, that is, as more and more
phosphate
and calcium are required. So it is not so hard to “infer”
vertebrates somewhere
along the way during evolution (following worms with, first,
calcium
carbonate and, later, calcium phosphate shells, i.e.,
mollusks).
Remembering that teeth are largely made of apatite as well,
we easily
infer an emphasis on teeth. Perhaps it is not so hard “to
infer dinosaurs”
after all at the end of an evolutionary sequence emphasizing
muscle,
bone, and teeth and including predatory fish, amphibians,
and reptiles.
THE “FEROCITY
OF CA AND P”
If we take seriously the suggestion in the previous section
that the inextricable
progression of life will naturally lead to something like
dinosaurs,
what we are doing is saying that these organisms are merely
an
evolutionary manifestation of the way certain particular
elements manifest
themselves in living tissue, for example, phosphorus and
calcium.
One might go further and argue that this manifestation as
dinosaurs
reflects the potential “ferocity of Ca and P.” It is
presaged by predatory
fish, amphibians, and reptiles. This view is not lessened by
contemplation
of the more recent mammalian predators instead. Watching a
videotape of a lion making a kill we clearly see the
ferocity of muscle
and bone and tooth.
In this regard, it is sobering to consider the evolving role
of silicon.
As mentioned earlier, Si is not fit for an essential
biological role. While
Si is more abundant than C, C is nevertheless far more
suited as a constituent
of living molecular matter. We do find Si in the very sharp
404 Zygon
spines of some cacti and in several other plants where it
serves to
strengthen stems and leaves and perhaps to inhibit
herbivores by wearing
down their teeth as they eat these gritty plants. With the
advent of
humans, evolution has taken a new direction because of the
enormous
human impact on the environment. Recently, Si (along with Cu
[copper],
which has had several earlier impacts, e.g., the bronze age
and the
electrified twentieth century) has entered this evolutionary
process in a
dramatic new way through micro-electronics, computers, and
the
Internet. While we cannot neglect the multifarious benefits
of glass
(silicates) and the wonderous contributions of computers, it
is not
obvious that this new role for Si (and Cu) will not,
instead, add to the
ferocity of Ca and P.
NOTES
1.
Mole: That amount of a given substance or species having a mass in grams
numerically the
same
as its molecular or atomic weight; now defined equivalently in the
International System of
Units
as the quantity of specified elementary entities (molecules, ions, electrons,
or the like) that in
number
equals the number of atoms in 0.012 kilograms of carbon 12 (A
Supplement to the Oxford
English
Dictionary, ed. R. W. Burchfield, [Oxford: Oxford
University Press, 1976], s.v. Mole).
2.
All proteins are made up of twenty different building blocks known as amino
acids, combined
linearly
in various ways. Each amino acid contains a residue, or group, that gives it
its
identity.
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