Thomas R. Cech provided evidence of the process of chemical evolution when he demonstrated that RNA can act as an enzyme to catalyze biochemical reactions.

In the 1920’s, Aleksandr Ivanovich Oparin and J. B. S. Haldane independently proposed that the early Earth atmosphere lacked oxygen but contained an abundant amount of hydrogen-containing compounds, such as ammonia, methane, water vapor, hydrogen gas, hydrogen cyanide, carbon monoxide, carbon dioxide, and nitrogen. They both proposed that these gases spontaneously combined in the presence of energy. There was no lack of energy on the surface of the early Earth because of volcanic eruptions, lightning, and ultraviolet radiation. Oparin and Haldane hypothesized that it was in this type of environment a reducing atmosphere without oxygen present that life on Earth began. Enzymes
[kw]Cech Demonstrates That RNA Can Act as an Enzyme (1982)
[kw]RNA Can Act as an Enzyme, Cech Demonstrates That (1982)
[kw]Enzyme, Cech Demonstrates That RNA Can Act as an (1982)
RNA
Enzymes
[g]North America;1982: Cech Demonstrates That RNA Can Act as an Enzyme[04750]
[g]United States;1982: Cech Demonstrates That RNA Can Act as an Enzyme[04750]
[c]Science and technology;1982: Cech Demonstrates That RNA Can Act as an Enzyme[04750]
[c]Biology;1982: Cech Demonstrates That RNA Can Act as an Enzyme[04750]
[c]Chemistry;1982: Cech Demonstrates That RNA Can Act as an Enzyme[04750]
Cech, Thomas R.
Zaug, Arthur J.
Inoue, Tan

Their model was tested in 1953 by Stanley L. Miller, Miller, Stanley L. a graduate student at the University of Chicago. He built a system of interconnecting tubes and flasks designed to simulate the primitive Earth atmosphere and primordial ocean. After a week, he analyzed the results and found simple organic acids and amino acids, Amino acids the building blocks of proteins. Proteins Miller’s experiment paved the way for others. Utilizing different mixtures of gases, later researchers produced virtually all the organic building blocks necessary for life and found in cells, including nucleotides, sugars, and fatty acids.

Once all the building blocks were formed, the next important step was to link these simple molecules into long chains, or polymers. Polymers An example of polymerization would be the linking of amino acids to form a long chain called a protein. Another polymer would be the polynucleotide, a long chain of single nucleotides. There are two types of nucleotides, deoxyribonucleic acid (DNA) DNA and ribonucleic acid (RNA), which are very similar in structure. They differ in that DNA contains the pentose sugar deoxyribose, whereas RNA contains the pentose sugar ribose. Ribose has a hydroxyl group, OH, instead of a hydrogen atom, H, at the number 2 carbon atom. DNA also contains the four nucleotide bases adenine (A), guanine (G), cytosine (C), and thymine (T), whereas RNA contains the same nucleotide bases as DNA except that uracil (U) replaces thymine.

Thomas R. Cech.

(The Nobel Foundation)

Many hypotheses suggest the early polymers may have been formed by different mechanisms. One means by which the organic molecules might have been concentrated is the process of evaporation. Another possibility is that clay particles in the soil, with their characteristic charges that attract and adsorb ions and organic molecules to their surfaces, might have brought early organic molecules close enough to one another that they could polymerize into long chains. The adsorbed metal ions also might have provided a site for the formation of polynucleotides. Polynucleotides Once the polynucleotides formed, they then could have acted as templates specifying “complementary sequences” for the formation of new polynucleotides. These complementary sequences would have resulted from the preferential bonding of certain nucleotides to one another (such as adenine with uracil or thymine, and guanine with cytosine). Geneticists have long known that this simple mechanism accounts for the transfer of genetic information from cell to cell and generation to generation.

The process of polymerization of nucleotides is slow and relatively ineffective; it would have been hindered by the conditions found on the primitive Earth. Even the clay and metal ions would have been slow. Currently, enzymes, which are proteins, function to catalyze (speed up the biochemical reactions involved in) the formation of polynucleotides. In the prebiotic solution or “primordial soup” of the early Earth, however, these enzymes would not yet have been present.

A discovery in 1981 by Thomas R. Cech and Arthur J. Zaug indicated how the early polynucleotides might have been replicated. RNA was thought to be a simple molecule, but now this appears not to be the case. Research with the ciliated protozoan Tetrahymena thermophila
Tetrahymena thermophila showed the existence of an RNA molecule with catalytic activity. Ribosomal RNA (rRNA) Ribosomal RNA is synthesized as large molecules, which are then spliced to the correct size. In Tetrahymena, the surprise came when this reaction was found to occur without the presence of proteins to catalyze the reaction. The only requirements for the reaction to occur were magnesium ions and the nucleotide guanosine triphosphate (GTP). This was a surprising result because in 1981 the dogma in science stated that enzymes were proteins and catalyzed all the reactions of a cell.

Cech later showed that the RNA molecule contained the catalytic activity to splice itself. This self-splicing mechanism resembled the activity of an enzyme, and Cech coined the term “ribozyme” to describe the RNA enzyme. A ribozyme Ribozymes is distinguished from an enzyme because it works on itself, unlike other enzymes, which work only on other molecules. Later, Cech studied the properties of the ribozyme and found it similar to enzymes in that it accelerated the reaction and was highly specific. In addition, the three-dimensional structure, as in enzymes, was found to be critical in the activity of the ribozyme. Cech’s research showed that if the ribozyme was put in a solution that prevented folding, then the ribozyme showed no catalytic activity, similar to any other enzyme.

The mechanism still needed refinement. Knowing that the folding was important in the catalytic activity aided in discovering the process. Cech and colleagues Brenda L. Bass, Bass, Brenda L. Francis X. Sullivan, Sullivan, Francis X. Tan Inoue, and Michael D. Been Been, Michael D. discovered that the folding was essential in creating binding sites for GTP. This also activated the phosphate group and increased the likelihood for splitting the RNA molecules. The reaction catalyzed by the ribozyme was speeded up by a factor of 10 billion. Thus, the ribozyme was established as having many enzymelike properties, such as accelerating the reaction and having a three-dimensional structure like an enzyme. It was observed that the ribozyme kept acting on itself. A true catalyst is not converted in the reaction, and the ribozyme was altered in the reaction. In 1983, this distinction also appeared. Zaug and Cech began working with Tetrahymena so that a shortened form of the RNA intron could work as a true enzyme.

Another surprise came out of this research. As the ribozyme acted as an enzyme by splicing another RNA chain, it also was synthesizing a nucleotide polymer of cytosine. Not only was the ribozyme acting as a splicer, it was also behaving as a polymerase enzyme by synthesizing chains of RNA molecules that were up to thirty nucleotides long. Later, other researchers strung together strings of nucleotides up to forty-five nucleotides long. These results led to the implication that RNA can duplicate RNA genes.

In 1982, sequences of RNA molecules, introns Introns (intervening sequences in genes), were found to be similar in different types of cells, such as fungi (yeast and Neurospora crassa) and protozoans. Remarkably, this discovery of a self-splicing RNA molecule was also found in a bacterial virus. This was a startling discovery, because fungi, protozoans, and viruses were thought to be only very distantly related. A conserved sequence implies an essential function even in the face of evolutionary divergence. This indicates the ribozyme may have evolved relatively early in the evolution of life.

Thomas Cech’s work led to geneticists’ current understanding of how RNA can duplicate RNA. These conclusions had a profound impact on the theory of the origin of life and chemical evolution. The fact that RNA can act as a catalyst supported the now widely accepted theory of an “RNA world” RNA world in which RNA was the primordial genetic material. These functions have now been taken over by DNA and proteins. Oparin, Aleksandr Ivanovich
Haldane, J. B. S.
RNA

It is now known that RNA and DNA store genetic information, but only RNA, as shown by Cech, can act as a catalyst to speed up chemical reactions. Cech’s discovery of splicing of RNA by RNA implies that proteins that may have been in existence might not have been needed for gene duplication. The self-splicing of RNA can be considered a primitive form of genetic recombination, since new combinations of RNA sequences are thereby created. Thus, the first genes are thought to be composed of RNA. RNA genes that were combined in a molecule that provided useful products could be at an advantage in the primordial mix.

Cech’s discovery that RNA can replicate itself also led researchers to speculate that RNA might catalyze other reactions. Although RNA does not exhibit a high rate of catalytic activity, even a modest rate and some specificity would have been faster than what would have occurred with no enzyme at all.

It is therefore believed that RNA had a significant role to play in the the evolution of life beyond self-replication. If primitive cells, which were surrounded by a membrane, contained these ribozymes, they would have been at a selective advantage over other such cells. Thus, the primitive genetic material of these cells would have been duplicated and passed to other cells. In addition, ribozymes could also bind amino acids in close proximity to allow the amino acids to combine into short polypeptides. These polypeptides Polypeptides could then act as a primitive enzyme, and if they aided the cell in replication and survival of RNA, then the cell could split and pass the genes on to other cells.

Cech’s work established a plausible scenario in which RNA might have been the primordial genetic material and enzyme. These functions have been taken over by DNA and proteins, but they are linked together by RNA. The specifics of how life started still remain a mystery, but the pieces of the puzzle are coming together. Cech received the 1989 Nobel Prize in Chemistry for this work; he shared it with Sidney Altman, who independently and nearly simultaneously discovered the catalyst RNase P, RNase P which consists of both protein and RNA, and demonstrated that the RNA is the catalytic part of the molecule. RNA
Enzymes

• Alberts, Bruce, et al. Molecular Biology of the Cell. 2d ed. New York: Garland, 1989. Advanced biology text includes an easy-to-understand introductory chapter titled “The Evolution of the Cell.” Covers the sequence of events in the possible evolution of the cell and Cech’s impact on the theory of chemical evolution.
• Amato, I. “RNA Offers a Clue to Life’s Start.” Science News 135 (June 17, 1989): 372. Discusses the research indicating that RNA can copy itself without assistance and summarizes the developments up to 1989 in this area of research. Written in a nontechnical manner.
• Campbell, Neil A. Biology. 7th ed. Redwood City, Calif.: Benjamin Cummings, 2005. Introductory college textbook presents easy-to-understand discussion of the origins of life on Earth, including chemical evolution and the possible sequence of events. References are found at the end of each chapter for further reading. Includes illustrations, diagrams, and glossary.
• Cech, Thomas R. “Ribozyme Self-Replication.” Nature 339 (June 15, 1989): 507-508. Short article is technical, but its introduction and conclusions provide easily understood information on the implications of RNA’s role in the evolution of life.
• _______. “RNA as an Enzyme.” Scientific American 225 (November, 1986): 64-75. Provides a nice review of the research Cech has done and the implications of his results.
• Gesteland, Raymond F., Thomas R. Cech, and John F. Atkins, eds. The RNA World. 3d ed. Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press, 2005. Collection of technical essays provides comprehensive coverage of the most current research into the role of RNA.
• Horgan, John. “The World According to RNA.” Scientific American 274 (January, 1996): 27-30. Brief article reports on experimental findings that indicate the importance of RNA’s role in the evolution of life on Earth.

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