Structural Biochemistry/RNA World Hypothesis

Background

The RNA World Hypothesis speculates that the origin of life began with ribonucleic acid (RNA) because of its ability to serve both as a storage for genetic information and enzymatic activity. It is proposed that RNA preceded the current genetic material, deoxyribonucleic acid (DNA), and led the evolution of the DNA → RNA → protein world.

There are two schools of thought that both support the RNA World hypothesis:

1. According to the Genetic Takeover Hypothesis, an earlier form of life on earth used RNA as its only genetic component. This proposes that there may be a pre-RNA molecule that used RNA or by change created RNA as a side product.

2. The first form of life on earth used RNA as its only genetic component. This theory requires that RNA came from inanimate matter.

History

The book, The Genetic Code, written in 1967 by Carl Woese, was the first published material that supported RNA World Hypothesis. Francis Crick and Leslie Orgel proposed the idea that RNA once did the work of DNA and proteins in 1968. Their theories were not validated until the work of Nobel Prize laureate Thomas R. Cech. In the 1970s, Cech was studying the splicing of RNA in a single-celled organism, Tetrahymena thermophila, when he discovered that an unprocessed RNA molecule could splice itself. He announced his discovery in 1982 and became the first to show that RNA has catalytic functions. The phrase “RNA World Hypothesis” was then coined later in 1986 by Harvard molecular biologist and Nobel Prize laureate Walter Gilbert as he commented on the recent observations of the catalytic properties of RNA. Another major milestone occurred in 2000 when it was published in Science that "The Ribosome is a Ribozyme" and the proteins in the ribosomes exist primarily on the periphery.

Theory

The primordial soup that made up Earth had compounds including nucleotides. These nucleotides sequenced spontaneously and randomly, eventually forming an RNA molecule (or a similar molecule) with catalytic characteristics. RNA has properties of autocatalytic self-replication and assembly, contributing to its exponential increase in number. Scientists today have assumed that replication was not perfect in the time of primitive life, and therefore variations of RNA developed. RNA's catalytic properties do not only apply to itself, but it also catalyzes transesterification-- a process necessary for protein synthesis that allows specific peptide sequences and proteins to arise. Some of the peptides formed may have supported the self-replication of RNA and provided the possibility of undergoing modifications. Those modifications led to more efficient sequences of RNA molecules.

A possible model for forming purine and pyrimidine bases was proposed by Urey and Miller's experiment. This experiment brought about evidence that organic molecules originated from inorganic ingredients such as carbon dioxide, ammonia, and water etc. Such products were mixed under a reduced environment and subjected to electric shock (via lightning), which led to the creation of more reactive molecules, such as hydrogen, cyanide, and aldehydes, as well as some amino acids and organic acids over a certain period of time. These amino acids contributed to the formation of peptide sequences.

http://www.smithlifescience.com/MillersExp.htm (see apparatus)

Proof that the RNA World Hypothesis has clout is found through the function of present day ribosomes. RNA is the ribosome's tool for synthesizing proteins and catalyzing the formation of peptide bonds. Therefore, this points to the fact that RNA is multifunctional, and can act as a synthesizer, transporter, messenger, and ribosome molecule.

One may ask, if RNA was the precursor of DNA and proteins, how did this evolution occur? DNA complements the RNA sequence and stores genomic information. Since DNA is a more stable molecule than RNA, it makes sense for DNA to adapt to the environment and take over this job of RNA. And how is DNA more stable than RNA? The difference between the general structure of DNA and RNA is found in the sugar. DNA has a deoxyribose sugar while RNA has a ribose sugar. The missing 2'-OH group on the deoxyribose sugar is what makes DNA more stable, since there is no hydroxyl group for other molecules to react with. Otherwise, RNA does not remain in a helical ring, as does DNA, since the chain of nucleotides would be easily broken apart. Another possibility scientists are exploring is the idea that reverse RNA transcriptase has a part in the RNA to DNA transformation. This transcriptase, found in retro-virus and HIV processes, in addition to RNA replicase, may be the enzyme that performed this transition. Furthermore, the combination of cyanoacetaldehyde and urea formed uracil (U) and cytosine (C)-- components of the primordial soup. This belief was supported by another of Miller's experiments. There is no evidence at this time that thymine (T), the nitrogenous base in DNA that takes the place of uracil (U) in RNA, was formed from this atmosphere. This infers that RNA was a predecessor of DNA. In addition, proteins that had formed from RNA were found to be versatile structures, allowing them to take over what was initially RNA's catalytic functioning.

RNA instability due to 2'OH.

Properties Supporting Hypothesis

Properties that support the RNA Hypothesis became more clear in the 1980s when it was discovered that RNA can activate and deactivate other molecules by binding with them while folding into specific structures. Before this discovery, researchers believed that RNA only had a few functions. Consideration of RNA as the pre-component of cellular life has since been studied extensively.

Major evidence that has the scientific community believing that RNA predates DNA and proteins are as follows:

- RNA has the ability to store genetic data, and pass down hereditary information.

- It is the main component linking up DNA and gene formation to amino acids and protein synthesis via transcription and translation.

- RNA's ability to duplicate itself as well as the genetic information it carries, very much like DNA.

- RNA's complexity is less than that of DNA, and involves fewer types of molecules in order to self-replicate.

- DNA requires an RNA primer in order to replicate while RNA does not need any such primer. This shows how DNA seems to depend more on RNA for its continued existence rather than the other way around.

- RNA is able to catalyze reactions as proteins do. The formation of a protein is also administered by RNA which points heavily to its preexistence over the proteins.

- RNA's ability to form double helices similar to DNA, and tertiary structures similar to those of catalytic proteins.

- The structure of RNA , with an hydroxyl group in the 2' position of the sugar molecule, makes it a less stable molecule which is capable of attacking a phosphodiester bond near it as long as the RNA molecule is in a flexible position and not constrained. This made it susceptible to breakdown and allowed an adaptation of different conformations which perhaps was beneficial to early life.

- RNA's different set of bases such as Uracil, which is “1 product of damage to cytosine” made RNA more prone to mutations thus making it more suitable to primitive life in early times.

The Miller-Urey experiment

An experiment supporting the RNA World Hypothesis was, the Miller-Urey Experiment. Where Stanley Miller and Harold Urey sealed water (H2O), methane (CH4), ammonia (NH3), and hydrogen (H2 inside a sterile array of glass tubes and flasks connected in a loop, with one flask half-full of liquid water and another flask containing a pair of electrodes. The liquid water was heated to induce evaporation, sparks were fired between the electrodes to simulate lightning through the atmosphere and water vapor, and then the atmosphere was cooled again so that the water could condense and trickle back into the first flask in a continuous cycle. Within a day, the mixture had turned pink in color,[1] and at the end of one week of continuous operation, Miller and Urey observed that as much as 10–15% of the carbon within the system was now in the form of organic compounds. Two percent of the carbon had formed amino acids that are used to make proteins in living cells, with glycine as the most abundant. Sugars and liquids were also formed. Nucleic acids were not formed within the reaction. But the common 20 amino acids were formed, in various concentrations.

In an interview, Stanley Miller stated: "Just turning on the spark in a basic pre-biotic experiment will yield 11 out of 20 amino acids."[2] This further supported the RNA World Hypothesis

Properties Opposing Hypothesis

Most of the opponents of the RNA World concentrate on dispelling the idea that RNA was the first form of genetic material, although they do agree that there may have been some other pre-RNA form of genetic material. In summary:

1. Ribose is relatively unstable and difficult to form in a prebiotic mixture. Despite the favorable and controllable conditions that are available in laboratory settings, pre-cellular life has never been created from inanimate matter.

2. The origin of life began roughly 300 million years ago. Some believe that this is too short of a time period for the prebiotic soup to evolve in to a pre-RNA or RNA World.

3. Lack of evidence of large amounts of polyphosphates in primitive Earth makes it unlikely that it was the source of prebiotic energy or that it was involved in the first genetic material. .

Others believe that RNA is not a likely pre-DNA form of genetic material. Their arguments include:

1. The limited catalytic capabilities of RNA. Theorists say that RNA needed to have had a multitude of catalytic abilities to be able to survive the prebiotic world, but RNA has not shown this. Proteins, on the other hand, do have those catalytic abilities via their varying, enzymatic abilities.

2. The prebiotic simulation of the formation of the RNA molecule has shown some difficulty in that the bases and the sugar molecule do not readily react in water.

3. Opponents advocate proteins over RNA because they are easily formed.

4. The probability of the right components of pre-cellular life to exist at the same place and time, without contaminates, and with the correct catalytic reactions is next to improbable .

5. Recent research shows that non-coding RNA regions have well-adapted and very specialized roles in the cell. Examples include siRNA and miRNA -- they work well in an environment where RNAi and mRNA already exist. Because of their usefulness that we are just beginning to understand, it makes it less likely that there are "relics" of the RNA World present in our DNA as Gilbert originally mentioned in 1986 .

Alternative Theories

The difficulty of RNA formation has caused other propositions of alternative theories on precursor materials for cellular life:

- Peptide Nucleic Acid theory (PNA), a nucleic acid with a backbone of peptide bonds, made a likely theory because it overcame the problem in RNA theory regarding the difficulty of RNA to attach ribose and phosphate groups together.

- Threose nucleic acids are proposed as a more likely starting material than RNA.

- Glycold nucleic acids are proposed as precursors rather than RNA because they are easily formed.

- Double origin theory suggests that both RNA and proteins existed around the same time independently.

References

1. ^ Gesteland, R.F., Cech, T.R., Atkins, J.F., 2006, The RNA World: the nature of modern RNA suggests a prebiotic RNA, Cold Spring Harbor Laboratory Press, United States of America, 768 p.
   
2. ^ Gilbert, W., "The RNA World". Nature 618.
   
3. ^ Altman, S. The RNA World
   
4. ^ Lazcano, A, Miller, S.L., "The Origin and Early Evolution of Life: Prebiotic Chemistry, the Pre-RNA World, and Time" Cell, Vol. 85, 7930798, June 14, 1996.
5. ^ RNA World Hypothesis at NationMaster.com
6. ^ RNA World Hypothesis at ExperienceFestival
7. ^ Eddy, S.R., "Non-Coding RNA Genes and the Modern RNA World" Nature Reviews: Genetics Vol. 2, Dec. 2001.

8.http://www.smithlifescience.com/MillersExp.htm

9.Nelson, David L. Principles of Biochemistry, 4th ed. W. H. Freeman, 2004.

10.http://www.helsinki.fi/~matpitka/articles/prebiotic.pdf

11.http://www.nationmaster.com/encyclopedia/RNA-world-hypothesis#History

12.Asimov, Isaac (1981). Extraterrestrial Civilizations. Pan Books Ltd. pp. 178. http://www.accessexcellence.org/WN/NM/miller.php

13.http://www.experiencefestival.com/a/RNA_world_hypothesis_-_The_base_pair/id/4697160

14.http://www.nationmaster.com/encyclopedia/RNA-world-hypothesis#Support