The RNA World the RNA World Hypothesis Suggests That Life On

The RNA world

The RNA world hypothesis suggests that life on Earth began with a simple RNA molecule that could copy itself without help from other molecules.

Yarus first describes the basis of Darwinian evolution, in which the “secret is selection”. He explains how differences in the sequence of the RNA found in an organism's ribosomes — part of the protein-making machinery of the cell — are used to classify it into one of the three kingdoms of life. He introduces LUCA, the Last Universal Common Ancestor, “behind or before which lies the RNA world”.

Yarus lays out the talents of RNA. As a molecule that is stable, single-stranded and able to form complex structures, it can assume many roles. Ribosomal and transfer RNAs provide the scaffolding to help make proteins and translate the information held in messenger RNA, which itself transcribes the information coded in DNA. The ribonucleotide building blocks that make up RNA are essential for enzyme function, and there are RNAs that have their own catalytic activity, known as ribozymes. Other recent discoveries have revealed the existence of small RNAs, in including microRNAs, that are intimately involved in controlling gene expression and translating messenger RNA. But the fact that RNA can adopt this vast catalogue of forms is insufficient evidence for a precursor RNA world. More compelling is the ability of RNA to evolve under selection pressure, this evolutionary adaptability may be why it is the nucleic acid of choice for the genome of some of the most difficult and changeable pathogens, such as the influenza viruses. It is a key part of the argument that it was RNA that generated subsequent life forms, and that RNAs were a primitive system for making short chains of amino acids — a system that evolved to produce the protein-based structural and metabolic machinery found in organisms today.

Further proof for the primitive RNA world could come from next-generation sequencing platforms that allow deep sampling of nucleic-acid populations from microorganisms in exotic locations, such as in deep-sea volcanic vents. But at present, the RNA world remains conjecture, based on powerful observations that this book captures.

DNA, RNA, and proteins are central to life on Earth. DNA stores the instructions for building living things—from bacteria to bumble bees. And proteins drive the chemical reactions needed to keep cells alive and healthy. Until recently, RNA was thought of as little more than a messenger between DNA and proteins, carrying instructions as messenger RNA (mRNA) to build proteins. However, RNA can do far more. It can drive chemical reactions, like proteins, and carries genetic information, like DNA. And because RNA can do both these jobs, most scientists think life as we know it began in an RNA world, without DNA and proteins.

RNA offspring

All living things reproduce. They copy their genetic information and pass it onto their offspring. And for RNAs to start life, they needed to reproduce too. This is why scientists think that the RNA world took off when an RNA emerged that could make copies of itself. As it did, new self-copying RNAs emerged. Some were better at copying themselves than others. The RNAs competed against each other, and the most successful won out. Over millions of years, these RNAs multiplied and evolved to create an array of RNA machines. At some stage, DNA and proteins evolved. Proteins began to drive chemical reaction in cells, and DNA—which is more stable than RNA—took the job of storing genetic information.

Nucleotide-Building RNA

The first RNAs were likely made using free-floating nucleotides that emerged in a primordial soup of molecules. Maintaining enough RNA building blocks (nucleotides) would have been a top priority in the RNA world. Scientists think nucleotide-building RNAs evolved on early Earth to provide nucleotides for building new RNAs.

Supplying the RNA world

According to the RNA world theory, the first RNAs were made using free-floating nucleotides that emerged in a primordial soup of molecules. They bonded together to make strands of RNA that weren’t very stable and degraded quickly. But some were more stable than others; these RNAs grew longer and bonded nucleotides more quickly. Eventually, RNA strands grew faster than they broke down—and this was RNA’s foot in the door. Over millions of years, these RNAs multiplied and evolved to create an array of RNA machines that are the basis of life as we know it today. But for RNA molecules to take hold, they would have needed an abundant supply of nucleotides. And scientists think nucleotide-building RNAs evolved to provide these RNA building blocks.

Biologists used to view RNA as a lowly messenger — the molecule that carries information from DNA to the protein-building centers of the cell. But discoveries since the early 1980s have shown that RNA can do much more. In addition to carrying genetic information, RNA can fold up into a complex structure that catalyzes a chemical reaction or binds another molecule, linking up with it in a way that allows the other molecule to be identified, activated, or deactivated. A key step in the origin of life was the evolution of a molecule that could copy itself. Once it was discovered that RNA could both carry information and cause chemical reactions (like those that would be required to copy a molecule), RNA became the prime suspect for the earliest self-replicating molecule. In fact, biologists hypothesize that early in life's history, RNA occupied center stage and performed most jobs in the cell, storing genetic information, copying itself, and performing basic metabolic functions. This is the "RNA world" hypothesis. Today, these jobs are performed by many different sorts of molecules (DNA, RNA, and proteins, mostly), but in the RNA world, RNA did it all.

The “RNA World” hypothesis, proposed in the end of 1960s by those who dealt with the origin and evolution of the genetic code helped solve this chicken–egg dilemma. The hypothesis postulated that the set of RNA molecules was the first chemical system on Earth able to reproduce itself. In fact, the hypothesis is underlain by two postulates. Firstly, at the initial stages of life there existed the RNA molecules which performed all the functions necessary for the reproduction and proliferation of biological molecules—informational, catalytic and structural. Secondly, at a certain stage of the “RNA World” development the above functions have separated, the systems have complicated, and the transition to the modern world of living systems has occurred. According to this idea, some types of RNA molecules must have had the catalytic functions, since it is only these functions that might have led to the formation of the specific world of self-replicating RNA molecules and their derivatives as a basis for the evolution of the primary biosphere. The discovery in 1982 of ribozymes, the polynucleotides consisting, at least, of 40–160 nucleotides and exhibiting the catalytic functions, has become a critical argument in favour of this idea. In a few years, Thomas Cech and Sidney Altman have shared the Nobel prize for the discovery of ribozymes, and, after another Nobel laureate, Walter Gilbert, the hypothesis has been ultimately christened the “RNA World”. There is both chemical and biological evidence in favour of this hypothesis which entices, first of all, by emphasizing the functional properties of the RNA molecules. Representing polynucleotides consisting of as little as four subunits, RNA, like proteins, can form tertiary structures of different complexity and catalyse a wide range of chemical transformations.

In short, the RNA molecules possess the following set of functions intrinsic both to DNA and proteins:

1. Encoding: RNA, analogous to DNA, may contain the protein synthesis programs 2. Replicative: copying, analogous to DNA, the nucleotide sequences

3. Structural: RNA, analogous to proteins, can form tertiary structures

4. Recognizing: RNA can recognize and specifically interact with the other macromolecules and ligands

5. Catalytic: RNA can perform specific catalysis of chemical reactions (ribozymes).

Problem of RNA world hypothesis

In spite of the great popularity of the “RNA World” hypothesis, there is a growing body of evidence indicating the presence of the obstacles which make this hypothesis highly improbable. The four main problems of chemical and informational nature deserve to be dwelt upon below.

The problems associated with the RNA world hypothesis are well known. The “RNA World” hypothesis is based on two postulates. (1) At the initial stages of life, RNA molecules performed all the functions necessary for the reproduction of biological molecules: informational, catalytic and structural; (2) At a certain stage of evolution, there occurred a functional separation of RNA and DNA, emergence of genetically encoded proteins and transition to the modern world of living systems. However, the analysis shows that the “RNA World” hypothesis suffers from a number of insurmountable problems of chemical and informational nature.

The biggest of them are:

(a) unreliability of the synthesis of starting components.

(b) catastrophically increasing instability of the polynucleotide molecules as they elongate.

(d) lack of the mechanism that would generate membrane-bound vesicles able to divide regularly and permeable to the nitrogenous bases and other RNA components.

(e) absence of driving forces for the transition from the “RNA world” to the much more complex “DNA-RNA world”.

Firstly, chemical nucleotide synthesis; secondly, polynucleotide chain formation; thirdly, replication reliability with polynucleotide chain elongation; fourthly, meaningfulness of randomly arising molecular chains. Therefore, the “RNA World” scenario is highly improbable.