lpetrich
01 Apr 2009, 07:29 PM
The RNA world hypothesis states that the DNA-RNA-protein organisms of the present-day world had some ancestors in which RNA both transmitted genetic information and acted as enzymes.
This hypothesis is partially motivated by the chicken-and-egg conundrum presented by the DNA-RNA-protein system. DNA contains master copies of genetic information, RNA contains intermediate copies and assists in assembling proteins, and proteins due most of the catalytic and structural work. In fact, proteins do nearly all the work of assembling the building blocks of all the macromolecules.
But can this system be simplified? It looks like an excellent example of irreducible complexity, a multipart system whose parts cannot function in isolation. However, it has often been possible to find intermediates that can easily be modified to yield the irreducibly-complex system. A parallel macroscopic system is honeybee societies, where queens are dependent on workers for just about everything, including founding new hives. But in many species, like bumblebees, lone queens found hives and raise the first generation of workers. So if queens start taking workers with them to found hives, one gets the honeybee swarming approach.
Proteins?
They are very versatile molecules, but it is hard to create a self-replicating protein. It is much easier with nucleic acids; in fact, Watson and Crick first recognized a simple mechanism for that when they worked out the double-helix structure of DNA in 1951-1953.
DNA?
It is more chemically stable than RNA, but it is only used as a master copy. So a DNA-first approach would have required replacement of DNA in all but one function, without leaving any vestigial uses behind.
RNA?
Unlike DNA, and despite its lesser chemical stability, it has several functions.
Messenger RNA
It carries a gene sequence from the genome to the ribosomes, which act as workbenches for assembling proteins.
Transfer RNA
One end is for matching the messenger RNA, and the other end is for holding the amino acid for a protein.
Ribosomal RNA
These molecules are the most essential part of ribosomes, with ribosomal proteins mainly acting as scaffolding.
Stray RNA
There are lots of bits of RNA that appear in contexts where one may not expect RNA to be present. These are reasonably interpreted as vestigial features of a former RNA world.
A short strand of RNA is needed as a primer for the enzyme DNA polymerase, which helps assemble DNA molecules (why RNA and not DNA?).
Bits of RNA are present in several cofactors, molecules that work with enzymes, like
NAD, NADP (electron transfer; can add/subtract hydrogen)
FAD, FMN (electron transfer; can add/subtract hydrogen)
Coenzyme A (acetate)
Vitamin B12 (methyl groups)
An RNA nucleotide is present in the energy intermediate ATP (adenosine triphosphate); the energy is in the phosphate-phosphate bonds and the adenosine is most likely a handle for the enzymes that work with it.
DNA nucleotides are all made from RNA ones, by turning an -OH into a -H in the ribose, and then adding a methyl group to the uracil to make thymine.
Ribozymes
In the 1980's, Thomas Cech was researching RNA splicing, and in 1986, he discovered some RNA that could splice itself without any assistance from any proteins. This startling discovery won him a Nobel Prize in 1989. Since then, several other ribozymes have been both discovered and made in labs. Ribosomes have also turned out to be a kind of ribozyme.
No DNA counterparts, deoxyribozymes or DNAzymes, have ever been found in the wild; they have all been made in various labs.
RNA-world Metabolism and Biosynthesis
One can identify some RNA-world metabolic capabilities, notably electron transfer (reduction-oxidation or redox reactions), methyl-group transfer, acetyl-group transfer, etc.
Many RNA-world ribozymes likely had some modified bases, which likely broadened their catalytic capabilities. One can reasonably infer this from the modified RNA bases of our world, notably in transfer RNA. In that molecule, uridine (uracil+ribose) gets turned into pseudouridine in a few spots, some of its adenines sometimes get turned into inosine, etc. Likewise, the niacin part of NAD looks like a modified nucleic-acid base.
Departing from the RNA World
There were two main steps needed to depart from it: the development of DNA and the development of proteins.
DNA is a modification of RNA, one that is only used for master copies of genetic information. In fact, the authors of Did DNA replication evolve twice independently? (http://www.ncbi.nlm.nih.gov/pubmed/10446225) propose that the evolution of DNA replication had been incomplete when the ancestors of Bacteria and Archaea/Eukarya split. They propose that their most recent ancestor had a DNA-RNA genome, with replication by both DNA -> RNA and RNA -> DNA copying. Early Bacteria and Archaea/Eukarya then separately elaborated on this system to produce the DNA -> DNA systems of today.
Amino acids, the building blocks of proteins, likely started out as cofactors of ribozymes. But along the way, the ribozymes built fancier and fancier multi-amino-acid cofactors until those cofactors took over and became the primary enzymes. Thus, proteins emerged. And some of the protein-assembly ribozymes have survived as ribosomes.
Before the RNA World?
The RNA-world hypothesis does not address the question of its origin; we must turn to prebiotic chemistry for answers to that. In experiments with such chemistry, RNA bases can be readily formed, but ribose requires relatively unusual conditions.
For that reason, there has been work on possible RNA ancestors like pyranosyl RNA (p-RNA) and Peptide Nucleic Acids (PNA), which use something other than ribose as their "backbone" molecule. So the first organism could have been a p-RNA or a PNA one or some other such, with RNA resulting from ribose getting substituted for the original "backbone" molecule.
Although the origin of life continues to be an unsolved problem, the "RNA world" hypothesis significantly narrows the gap between known prebiotic chemistry and the first organisms.
This hypothesis is partially motivated by the chicken-and-egg conundrum presented by the DNA-RNA-protein system. DNA contains master copies of genetic information, RNA contains intermediate copies and assists in assembling proteins, and proteins due most of the catalytic and structural work. In fact, proteins do nearly all the work of assembling the building blocks of all the macromolecules.
But can this system be simplified? It looks like an excellent example of irreducible complexity, a multipart system whose parts cannot function in isolation. However, it has often been possible to find intermediates that can easily be modified to yield the irreducibly-complex system. A parallel macroscopic system is honeybee societies, where queens are dependent on workers for just about everything, including founding new hives. But in many species, like bumblebees, lone queens found hives and raise the first generation of workers. So if queens start taking workers with them to found hives, one gets the honeybee swarming approach.
Proteins?
They are very versatile molecules, but it is hard to create a self-replicating protein. It is much easier with nucleic acids; in fact, Watson and Crick first recognized a simple mechanism for that when they worked out the double-helix structure of DNA in 1951-1953.
DNA?
It is more chemically stable than RNA, but it is only used as a master copy. So a DNA-first approach would have required replacement of DNA in all but one function, without leaving any vestigial uses behind.
RNA?
Unlike DNA, and despite its lesser chemical stability, it has several functions.
Messenger RNA
It carries a gene sequence from the genome to the ribosomes, which act as workbenches for assembling proteins.
Transfer RNA
One end is for matching the messenger RNA, and the other end is for holding the amino acid for a protein.
Ribosomal RNA
These molecules are the most essential part of ribosomes, with ribosomal proteins mainly acting as scaffolding.
Stray RNA
There are lots of bits of RNA that appear in contexts where one may not expect RNA to be present. These are reasonably interpreted as vestigial features of a former RNA world.
A short strand of RNA is needed as a primer for the enzyme DNA polymerase, which helps assemble DNA molecules (why RNA and not DNA?).
Bits of RNA are present in several cofactors, molecules that work with enzymes, like
NAD, NADP (electron transfer; can add/subtract hydrogen)
FAD, FMN (electron transfer; can add/subtract hydrogen)
Coenzyme A (acetate)
Vitamin B12 (methyl groups)
An RNA nucleotide is present in the energy intermediate ATP (adenosine triphosphate); the energy is in the phosphate-phosphate bonds and the adenosine is most likely a handle for the enzymes that work with it.
DNA nucleotides are all made from RNA ones, by turning an -OH into a -H in the ribose, and then adding a methyl group to the uracil to make thymine.
Ribozymes
In the 1980's, Thomas Cech was researching RNA splicing, and in 1986, he discovered some RNA that could splice itself without any assistance from any proteins. This startling discovery won him a Nobel Prize in 1989. Since then, several other ribozymes have been both discovered and made in labs. Ribosomes have also turned out to be a kind of ribozyme.
No DNA counterparts, deoxyribozymes or DNAzymes, have ever been found in the wild; they have all been made in various labs.
RNA-world Metabolism and Biosynthesis
One can identify some RNA-world metabolic capabilities, notably electron transfer (reduction-oxidation or redox reactions), methyl-group transfer, acetyl-group transfer, etc.
Many RNA-world ribozymes likely had some modified bases, which likely broadened their catalytic capabilities. One can reasonably infer this from the modified RNA bases of our world, notably in transfer RNA. In that molecule, uridine (uracil+ribose) gets turned into pseudouridine in a few spots, some of its adenines sometimes get turned into inosine, etc. Likewise, the niacin part of NAD looks like a modified nucleic-acid base.
Departing from the RNA World
There were two main steps needed to depart from it: the development of DNA and the development of proteins.
DNA is a modification of RNA, one that is only used for master copies of genetic information. In fact, the authors of Did DNA replication evolve twice independently? (http://www.ncbi.nlm.nih.gov/pubmed/10446225) propose that the evolution of DNA replication had been incomplete when the ancestors of Bacteria and Archaea/Eukarya split. They propose that their most recent ancestor had a DNA-RNA genome, with replication by both DNA -> RNA and RNA -> DNA copying. Early Bacteria and Archaea/Eukarya then separately elaborated on this system to produce the DNA -> DNA systems of today.
Amino acids, the building blocks of proteins, likely started out as cofactors of ribozymes. But along the way, the ribozymes built fancier and fancier multi-amino-acid cofactors until those cofactors took over and became the primary enzymes. Thus, proteins emerged. And some of the protein-assembly ribozymes have survived as ribosomes.
Before the RNA World?
The RNA-world hypothesis does not address the question of its origin; we must turn to prebiotic chemistry for answers to that. In experiments with such chemistry, RNA bases can be readily formed, but ribose requires relatively unusual conditions.
For that reason, there has been work on possible RNA ancestors like pyranosyl RNA (p-RNA) and Peptide Nucleic Acids (PNA), which use something other than ribose as their "backbone" molecule. So the first organism could have been a p-RNA or a PNA one or some other such, with RNA resulting from ribose getting substituted for the original "backbone" molecule.
Although the origin of life continues to be an unsolved problem, the "RNA world" hypothesis significantly narrows the gap between known prebiotic chemistry and the first organisms.