The RNA world hypothesis describes an early Earth with selfreplicating and catalytic RNA but no DNA or proteins. This has spurred scientists to try to determine if relatively short RNA molecules could have spontaneously formed that were capable of catalyzing their own continuing replication. A number of hypotheses of modes of formation have been put forward. Early cell membranes could have formed spontaneously from proteinoids, proteinlike molecules that are produced when amino acid solutions are heated – when present at the correct concentration in aqueous solution, these form microspheres which are observed to behave similarly to membraneenclosed compartments. Other possibilities include systems of chemical reactions taking place within clay substrates or on the surface of pyrite rocks. Factors supportive of an important role for RNA in early life include its ability to act both to store information and catalyse chemical reactions as a ribozyme its many important roles as an intermediate in the expression and maintenance of the genetic information in the form of DNA in modern organisms and the ease of chemical synthesis of at least the components of the molecule under conditions approximating the early Earth. Relatively short RNA molecules which can duplicate others have been artificially produced in the lab. Such replicase RNA, which functions as both code and catalyst provides a template upon which copying can occur.
Jack Szostak has shown that certain catalytic RNAs can, indeed, join smaller RNA sequences together, creating the potential, in the right conditions for selfreplication. If these were present, Darwinian selection would favour the proliferation of such selfcatalysing structures, to which further functionalities could be added. Lincoln and Joyce identified an RNA enzyme capable of self sustained replication.Researchers have pointed out difficulties for the abiotic synthesis of nucleotides from cytosine and uracil. Cytosine has a halflife of days at °C °F and , years in freezing water. Larralde et al., say that the generally accepted prebiotic synthesis of ribose, the formose reaction, yields numerous sugars without any selectivity. and they conclude that their results suggest that the backbone of the first genetic material could not have contained ribose or other sugars because of their instability. The ester linkage of ribose and phosphoric acid in RNA is known to be prone to hydrolysis.A slightly different version of the RNAworld hypothesis is that a different type of nucleic acid, such as PNA, TNA or GNA, was the first one to emerge as a selfreproducing molecule, to be replaced by RNA only later. James Ferriss studies have shown that clay minerals of montmorillonite will catalyze the formation of RNA in aqueous solution, by joining activated mono RNA nucleotides to join together to form longer chains. Although these chains have random sequences, the possibility that one sequence began to nonrandomly increase its frequency by increasing the speed of its catalysis is possible to kick start biochemical evolution.
History
The phrase RNA World was first used by Nobel laureate Walter Gilbert in , in a commentary on recent observations of the catalytic properties of various forms of RNA. However, the idea of independent RNA life is older and can be found in Carl Woeses book The Genetic Code. In , the molecular biologist Alexander Rich, of the Massachusetts Institute of Technology, had posited much the same idea in an article he contributed to a volume issued in honor of Nobellaureate physiologist Albert SzentGyörgyi.In , Gilbert was awarded the Louisa Gross Horwitz Prize from Columbia University together with Frederick Sanger. In the following year, he was awarded the Nobel Prize in Chemistry with Frederick Sanger and Paul Berg. Gilbert and Sanger were recognized for their pioneering work in devising methods for determining the sequence of nucleotides in a nucleic acid. Walter Gilbert also first proposed the term RNA world hypothesis for the origin of life, for a concept first proposed by Carl Woese in . He is a cofounder of the biotech startup companies Biogen and Myriad Genetics, and was the first chairman on their respective boards of directors. He is also a member of the Board of Scientific Governors at The Scripps Research Institute. Dr. Gilbert is currently the chairman of the Harvard Society of Fellows.
Rich is the founder of Alkermes and has been its director since . Dr. Rich is CoChairman of the Board of Directors of Repligen Corporation, a biopharmaceutical company. He is also a member of the Board of Directors for Profectus BioSciences, Inc. He also serves on the editorial board of Genomics and the Journal of Biomolecular Structure and Dynamics.In , Rich discovered polysomes clusters of ribosomes which read one strand of mRNA simultaneously.In , Rich and coworkers at MIT accidentally grew a crystal of ZDNA. This was the first crystal structure of any form of DNA. After years of attempts, Rich et al. finally crystallised the junction box of B and ZDNA. Their results were published in an October Nature journal. Whenever ZDNA forms, there must be two junction boxes that allow the flip back to the canonical Bform of DNA.Deoxyribonucleic acid DNA is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms and some viruses. The main role of DNA molecules is the longterm storage of information. DNA is often compared to a set of blueprints or a recipe, or a code, since it contains the instructions needed to construct other components of cells, such as proteins and RNA molecules. The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in regulating the use of this genetic information.
Properties of RNA
The properties of RNA make the idea of the RNA world hypothesis conceptually possible, although its plausibility as an explanation for the origin of life is debated. RNA is known to form efficient catalysts and its similarity to DNA makes its ability to store information clear.A slightly different version of the hypothesis is that a different type of nucleic acid, termed preRNA, was the first one to emerge as a selfreproducing molecule, to be replaced by RNA only later. Such nucleic acids are sometimes more easily produced andor polymerized under prebiotic conditions. Suggestions for such nucleic acids include Peptide nucleic acid PNA, Threose nucleic acid TNA or Glycerol nucleic acidGNA .A nucleic acid is a macromolecule composed of chains of monomeric nucleotides. In biochemistry these molecules carry genetic information or form structures within cells. The most common nucleic acids are deoxyribonucleic acid DNA and ribonucleic acid RNA. Nucleic acids are universal in living things, as they are found in all cells and viruses. Nucleic acids were first discovered by Friedrich Miescher.
Artificial nucleic acids include peptide nucleic acid PNA, Morpholino and locked nucleic acid LNA, as well as glycol nucleic acid GNA and threose nucleic acid TNA. Each of these is distinguished from naturallyoccurring DNA or RNA by changes to the backbone of the molecule.The term nucleic acid is the generic name for a family of biopolymers, named for their role in the cell nucleus. The monomers from which nucleic acids are constructed are called nucleotides.Each nucleotide consists of three components a nitrogenous heterocyclic base, which is either a purine or a pyrimidine a pentose sugar and a phosphate group. Nucleic acid types differ in the structure of the sugar in their nucleotides DNA contains deoxyriboses while RNA contains ribose where the only difference is the presence of a hydroxyl group. Also, the nitrogenous bases found in the two nucleic acid types are different adenine, cytosine, and guanine are found in both RNA and DNA, while thymine only occurs in DNA and uracil only occurs in RNA. Other rare nucleic acid bases can occur, for example inosine in strands of mature transfer RNA.Nucleic acids are usually either singlestranded or doublestranded, though structures with three or more strands can form. A doublestranded nucleic acid consists of two singlestranded nucleic acids held together by hydrogen bonds, such as in the DNA double helix.
RNA as an enzyme
RNA enzymes, or ribozymes, are possible although not common in todays DNAbased life. However ribozymes play vital roles ribozymes are essential components of the ribosome, which is vital for protein synthesis. Many ribozyme functions are possible nature widely uses RNA selfsplicing and directed evolution has created ribozymes with a variety of activities.A ribozyme from ribonucleic acid enzyme, also called RNA enzyme or catalytic RNA is an RNA molecule that catalyzes a chemical reaction. Many natural ribozymes catalyze either the hydrolysis of one of their own phosphodiester bonds, or the hydrolysis of bonds in other RNAs, but they have also been found to catalyze the aminotransferase activity of the ribosome.RNA can also act as a hereditary molecule, which encouraged Walter Gilbert to propose that in the past, the cell used RNA as both the genetic material and the structural and catalytic molecule, rather than dividing these functions between DNA and protein as they are today. This hypothesis became known as the RNA world hypothesis of the origin of life.
Investigators studying the origin of life have produced ribozymes in the laboratory that are capable of catalyzing their own synthesis under very specific conditions, such as an RNA polymerase ribozyme. Mutagenesis and selection has been performed resulting in isolation of improved variants of the Round polymerase ribozyme from . B. is able to add up to nucleotides to a primer template in hours, until it decomposes by hydrolysis of its phosphodiester bonds.Some ribozymes may play an important role as therapeutic agents, as enzymes which tailor defined RNA sequences, as biosensors, and for applications in functional genomics and gene discovery.Although most ribozymes are quite rare in the cell, their roles are sometimes essential to life. For example, the functional part of the ribosome, the molecular machine that translates RNA into proteins, is fundamentally a ribozyme. Ribozymes often have divalent metal ions such as Mg as cofactors.
Comparison of DNA and RNA structure
The major difference between RNA and DNA is the presence of a hydroxyl group at the position of the ribose sugar in RNA. This group makes the molecule less stable—in flexible regions of an RNA molecule i.e., where not constrained in a double helix, it can chemically attack the adjacent phosphodiester bond to cleave the phosphodiester backbone. The hydroxyl group also forces the ribose into the Cendo sugar conformation unlike the Cendo conformation of the deoxyribose sugar in DNA. This forces a RNA double helix into a slightly different conformation than DNA.RNA also uses a different set of bases than DNA—adenine, guanine, cytosine and uracil, instead of adenine, guanine, cytosine and thymine. Chemically, uracil is similar to thymine, although its production requires less energy. In terms of base pairing this has no effect, adenine will readily bind uracil or thymine. Uracil is, however, one product of damage to cytosine making RNA particularly susceptible to mutations which replace a GC base pair with a GU wobble or AU base pair.
RNA and DNA are both nucleic acids, but differ in three main ways. First, unlike DNA which is doublestranded, RNA is a singlestranded molecule in most of its biological roles and has a much shorter chain of nucleotides. Second, while DNA contains deoxyribose, RNA contains ribose, there is no hydroxyl group attached to the pentose ring in the position in DNA. These hydroxyl groups make RNA less stable than DNA because it is more prone to hydrolysis. Third, the complementary base to adenine is not thymine, as it is in DNA, but rather uracil, which is an unmethylated form of thymine.Like DNA, most biologically active RNAs including tRNA, rRNA, snRNAs and other, noncoding RNAs are extensively base paired to form double helices. Structural analysis of these RNAs have revealed that they are highly structured. Unlike DNA, their structures do not consist of long double helices but rather collections of short helices packed together into structures akin to proteins. In this fashion, RNAs can achieve chemical catalysis, like enzymes. For instance, determination of the structure of the ribosome—an enzyme that catalyzes peptide bond formation—revealed that its active site is composed entirely of RNA.
