Number of words: 555

The extraordinary possibilities of evolution are the result of errors in replication. Mutations are critical. If the replication of RNA were error free, and perfect, no mutants would arise and evolution would stop. Nothing would change. There would be no living diversity. So mutations are required for life to emerge. Equally, however, evolution would be impossible if the error rate of replication was too high. The reason is that only some mutations lead to an improvement in adaptation. Most lead to deterioration.

By playing with the numbers, one finds that if too many mistakes occur in any one replication event, a population of RNA molecules will be unable to maintain enough meaningful information to pass to the next generation as the genetic message becomes scrambled. So when the mutation rate exceeds a sharply defined threshold, inheritance breaks down. Thus if a quasispecies of RNAs is suited to work well in an environment, once it moves past this threshold of error, any adaptation to that environment is impossible. Eigen and Schuster found that there was a way to figure out where this error threshold lies and express it as a maximum-possible sequence length that can thrive for any given mutation rate. Let’s say that there is a given probability of a spelling mistake when an RNA sequence reproduces. Naturally, the longer the RNA sentence, the more errors it will contain, just as the longer the sentence you attempt to spell out by hand the more of a chance there is of making a silly slip. So we can think of the error threshold as a length of RNA past which the ability to pass on genetic information is too degraded. For an RNA of 100 “letters” (chemical units called bases) the mutation rate has to be fewer than 1 in every 100 letters for the message to be passed down. And for an RNA of 1,000 letters, it has to be fewer than 1 in 1,000. Thus the maximum possible mutation rate per base must be less than the inverse of the genome length. That way, there will be enough descendants with the correct message to pass the information down the generations. Experiments by Leslie Orgel at the Salk Institute in San Diego on the spontaneous replication of RNA (without the help of enzymes) suggested that the error rate was around 1 in 20. That figure implies an upper limit on primitive genomes of about 20. Perhaps, with luck, the figure could be as high as 100. The bigger, the better. The reason is that the longer the RNA, the more opportunities there are to reduce the mutation rate, using RNA itself.

Single-stranded RNA often forms tangles where its component bases pair with themselves, notably in hairpin bends. The resulting complex shapes give it the ability to act as an enzyme—possibly to speed up chemical reactions that help correct errors. At the dawn of life, genetic replication might have been occurring very slowly, subject to high error rates, but perhaps primitive RNA enzymes emerged to help make replication more accurate by acting as a kind of template to arrange the chemical players in the game of replication. This is promising when it comes to creating a biochemistry that is complex enough to sustain life.

Excerpted from page 127-128  of ‘Super co-operators ’ by Martin Nowak