RNA World (Sidebar 3)

Review
DNA contains the genetic information necessary to make proteins. There are two main types of proteins—structural and functional. Different types of structural proteins make up our hair, skin, fingernails, muscles, and organs. Functional proteins, or enzymes, are the catalysts that cause the reactions in our cells to go in a preferred direction. Without enzymes, many reactions would occur, but at random, and at low frequency. Some other reactions, like DNA replication and transcription, require so many different protein enzymes, that they likely would never occur without protein enzymes.

Before mRNA can be translated to protein, it must be "processed" (i.e. some sections of the RNA are cut out and the others joined together). In eucaryotes and some viruses, mRNA contains introns and exons. Processing involves splicing (cutting) the introns out and attaching the exons together. Also, a "cap" is added to one end and a "tail" to the other end. The strand of exons can then be translated to a protein. For example:

The evolutionary need for the RNA world theory
In constructing a model for a naturalistic origin of the first functional organic molecules (DNA, RNA, and proteins), there is a "chicken and egg" problem. DNA contains the information necessary for making a meaningful protein. However, DNA is inert. To make proteins from DNA, many different enzymes are needed, even in the simplest systems in bacteria. DNA cannot replicate itself; proteins are required for that too. So, in other words, to make protein, you must have DNA, and to make DNA, you must have proteins. How then could DNA-based cells have arisen by random, natural processes?

RNA World
In the 1967, Carl Woese suggested in his book The Genetic Code that the first living systems were RNA-based, instead of DNA-based as they are now. He also proposed that the RNA molecules were self-catalyzing. Essentially, RNA would have been the first genetic material and the first enzyme, eliminating the need for DNA and proteins. In the 1980's it was discovered that some protozoa have RNA molecules with limited catalytic functions. These RNA molecules were called "ribozymes" to emphasize the dual nature of genetic information and enzymatic ability. Here are three examples of ribozyme activities:

1. Ribonuclease P is a complex of a protein and an RNA molecule in which the RNA catalyzes the cleavage of tRNA; 2. Certain virusoid RNA's have self-cleaving ability; 3. Group I introns can splice themselves out of pre-mRNA (see above)

All three of these reactions involve the cleavage of a phosphodiester bond (the type of bond between two nucleotides). The ribozyme provides the specificity (where to cut) and catalyzes the cleavage, but in vivo the reaction may require proteins.

Problems with the RNA World theory
1. RNA World theory requires that there was a pre-biotic pool of beta-D-ribonucleotides (RNA nucleotides in the proper configuration—adenine, cytosine, guanine, or uracil linked to the 1' position of ribose in the beta-configuration with a phosphate group attached to the 5' position of ribose).

Problems: a. There are many different ways that the molecules composing the bases (A, G, C and U) can be arranged, but only one way is correct in biological systems. b. For chemical evolution to occur, there would have had to be vast quantities of the four bases, phosphate groups, and ribose all in the proper configurations, but because there would have been so many destructive forces, there would likely have been only trace amounts at the most. c. The chemical pathway to making ribose produces formaldehyde as an intermediate. Nitrogenous substances would have reacted with formaldehyde and stopped the pathway, preventing the formation of ribose. d. Nitrogenous substances are required for the synthesis of the bases. The coincident conditions for the synthesis of ribose and bases are incompatible.

2. RNA World theory requires that the beta-D-ribonucleotides link together at the correct positions—3' carbon of one sugar links to the 5' carbon of the next sugar through the phosphate group.

Problems: a. The RNA nucleotides would not link together spontaneously; they need an energy source. b. The usual energy source, ATP, would not be formed in the prebiotic mix. c. If there were an energy source, the nucleotides would link together in the wrong positions: the primary product would be 5'-5'; the secondary product would be 2'-5'. Any linkage other than 3' to 5' would change the three dimensional structure. Only 3'-5' linkages are found in any biological organism. (See Figure 1) (Figure 1) d. Any RNA molecules formed would be quickly degraded by spontaneous hydrolysis. e. Addition of the wrong nucleotide would make the whole process useless because catalytic functions are based on the shape of the molecule, and the shape of an RNA molecule is based on the sequence of the nucleotides.

3. RNA World theory requires that an RNA polymer formed with the ability to replicate itself.

Problems: a. A self-replicating RNA molecule of at least 40 nucleotides would have to arise from the spontaneous arrangement of the RNA nucleotides. b. To propagate the RNA sequence that allows self-replication, the RNA molecule must replicate with high accuracy, or there must be another copy that can be a template. c. The self-replicating molecule should not replicate other irrelevant RNA molecules. In experiments to spontaneously replicate RNA, scientists have been able to make a complementary RNA but not a copy. The half-lives of nucleotide bases are short relative to their formation calling into question whether sufficient quantities could ever accumulate to form any polymers.

4. RNA World theory requires that the self-replicating RNA molecules had all the catalytic activities necessary to sustain a ribo-proto-organism.

Problems: a. The first "ribo-proto-organism," or organism precursor with RNA as both the information molecule and the enzyme, would need hundreds of different ribozymes with different enzymatic abilities to perform the metabolic processes. b. There is no evidence that any RNA molecules ever had any of these functions. c. RNA World has the same problem that the evolution of a DNA-based cell does—information found in the arrangement of specific sequences does not happen spontaneously.

Summary
Certain RNA molecules that are found in some viruses, protozoa, and fungi have the ability to cleave a phosphodiester bond. This catalytic ability has been used and extrapolated by some evolutionary scientists to demonstrate that the first biotic systems may have been RNA-based rather than DNA-based. The RNA-based organisms would have had the ability to carry information in their nucleotide sequence and to perform enzymatic functions. The evolution of this type of organism takes away the problem of the mutual reliance of DNA and protein. There are problems with this theory though. First, it is extremely unlikely that the proper molecules could spontaneously arise in the same conditions, and that there would be enough of them. Second, it is extremely unlikely that any RNA nucleotides that did form would spontaneously link together in the correct direction (3' bound to 5'). It is also doubtful that any RNA molecules that did link together would be in the correct sequence to be meaningful. Third, it is extremely unlikely that, of any RNA molecules that did form, one would have the ability to replicate itself with high accuracy. Fourth, it is extremely unlikely that there was a sufficient amount of catalytic RNA molecules to perform all the different enzymatic functions necessary for a self-contained organism.

References
Mills, Gordon and Kenyon, Dean. 1996. "The RNA World: a Critique." Origins and Design> 17:1 p.9 - 13.

Lewin, Benjamin. 1994. "RNA as catalyst: Changing the informational content of RNA" Genes V. Oxford University Press, New York.