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12. Life
| 12.20 |
Error rates from genetic copying
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| DNA replication is a high fidelity copying process, yet base substitutions and insertion/deletion events occasionally occur. Errors such as 'point mutations' (single base substitutions) are rare events, an incidence of about 1 base substitution for every 100 million to 100,000 million bases replicated. | ||
| More complex and even rare mutations can occur involving the insertion or deletion of one or more bases. If the insertions or deletions occur in the non-transcribed or 'flanking' regions of a gene they often have little genetic consequence; however if they occur in the region coding for amino acids the consequences are usually lethal because the protein sequence will now be quite different as insertion or deletion of bases | ||
| All genes in cellular organisms are double stranded DNA molecules which are replicated faithfully by a complex replication machine 9 consisting of about 30 to 40 different proteins). This high fidelity copying of DNA is achieved because a number of the DNA replicating proteins deal exclusively with editing and correcting the newly produced copy of DNA. | ||
| For example in DNA replication, if an A was inserted during copying instead of a C, the editor enzyme can detect this and reinsert the correct base, because the normal base pairing process has been disrupted. Further, if chemical damage to a base occurs after the newly synthesized strand has base paired to the parent (template) strand, a "kink" is caused in the double helix prompting the editing functions of the enzyme complex to snip out the damaged sequence and re synthesize a good copy. | ||
| It is akin to the process that occurs to check data integrity during electronic message transmission. This is why gene mutations occurring solely at the level of DNA are extremely rare events. | ||
| The mutations we see are those that have slipped through all of the normal editing and checking gates of the DNA replication machine. | ||
| 12.12.1 | Error rates from RNA copying | |
| Transcription, RNA replication and reverse transcription are error prone. | ||
| Thus- the picture we now have of the early RNA world is one almost of "evolving chaos"- the survival of the fittest self-replicating molecule. Manfred Eigen and colleagues have done some illuminating research that has demonstrated how error-prone copying in RNA and environmental selection for function might give rise to a quasi-optimal population of RNA molecules. This population of RNA molecules rapidly evolves in a darwinian manner to the changing environment. | ||
| In comparison with double stranded DNA, single stranded RNA is chemically much more unstable. | ||
| 12.12.2 | When error is an advantage | |
| For some RNA viruses such as influenza and the retro viruses, the high error rate inherent in RNA production, together with other genomatic strategies, provide a selective advantage. The high mutation rates ( a base error is generated for every 1000 or so bases replicated) enable evasion of the immune system of infected vertebrate hosts. This has led to the retention of RNA as the viral genome, long after the evolution of protein enzymes. | ||
| 12.12.3 | What came first DNA or RNA? | |
| The first living molecules were polymers of RNA. proteins as we now know them, and DNA containing chromosomes, did not exist. In the RNA world, the microscopic living forms were self-replicating RNA molecules of varying lengths, consisting of hundreds of thousands of bases. replication of the liner RNA strand was mediated by a folded version of the same molecule (ribozyme). Thus, the first molecules capable of self-replication and thus Darwinian evolution were not the DNA double helices as we understand them today. replication of such DNA helices requires a complex set of specific protein enzymes making up the 'DNA replication machine'. | ||
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