When most people, including scientists, even including evolutionary and molecular biologists, talk about evolution, they dwell on the critical aspects of variation and natural selection almost exclusively. These two processes are considered to be the heart and soul of the evolutionary process. But there is another process that must also exist for evolution to occur, and that is replication of the organism in the next generation. I am not talking about reproduction, which of course must occur. Replication is more than simply an organism reproducing itself. Replication is the means by which reproduction occurs with extreme accuracy, so that the characteristics of the original are inherited in the offspring. Replication is what makes inheritance possible. And the fact that replication is less than 100% accurate is what allows for the existence of variation, which is critical for evolution.
What we tend to overlook is that replication, while it cannot be perfect (so as to allow for variation), must be very, very good. If it weren’t, then whatever selective advantage an organism might have gained by a change in some allele would not be transmitted to the next generation, and no evolution would occur. If a bird had developed better vision than its siblings, that bird would have a great selective advantage during its own lifetime. But if that characteristic were not inherited by its offspring, evolution of better eyesight in that species would never happen.
Modern life replicates its phenotype with at least 99.99999% fidelity. This leaves enough room for naturally occurring errors (mutations) to produce the variation needed for Darwin’s theory to work. But what about the lower limit of replication fidelity? How good must replication be in order to avoid “error catastrophe”—which means, in this context, a level of error such that no selective advantage is possible?
The threshold for a mutation rate that would cause an error catastrophe has been determined theoretically and confirmed by experiment to be simply equal to the inverse of the size of the genome. Thus, if an organism has a genome of 10,000 bases, like some bacteria and viruses, a mutation rate greater than 0.0001 or 0.01% would lead to a loss of any selective advantage for the fittest organisms, and thus it would not allow for evolution to work. This seems like a very low mutation rate, and it is, but of course in large multicelled organisms with genomes in the billions of bases, the error rate is correspondingly lower. Since replication fidelity is equal to 1 minus the mutation rate, the minimal level of replication fidelity is 0.9999 for single-celled organisms, and 0.9999999 for animals and plants.
Are such high values for replication fidelity in early life reasonable to expect? Not when we consider that for even the most primitive modern organisms, replication, transcription and translation involves a host of error correction enzymatic processes, all of which had to evolve—but how could they if the prevailing error rate was too high to allow for evolution?
This seems to leave a large gaping hole in our attempt to understand the origin of life, particularly the origin of evolution. The best solution to this mystery is to posit some other type of evolutionary process whereby early primitive cells could replicate themselves (meaning their entire phenotype) with great accuracy that did not involve the extremely complex advanced mechanisms of DNA replication and DNA-directed protein synthesis. The RNA world (generally assumed to predate DNA world) doesn’t look much better. Even if we assume that the RNA-world genome is a set of RNA ribozymes, and that the smallest such self-replicating molecule might be as small as 50 bases, we still need to have a 98% accuracy in replication of RNA, which is far less than the 80% fidelity (at best) observed in lab experiments. We have no idea what such an alternative evolutionary mechanism not working with replicating nucleic acid polymers might consist of.
But we can still address the fundamental question of replication fidelity evolution even if we have no idea how that evolution could have occurred. I recently completed a study of a simulation model for studying replication fidelity in early life that makes no assumptions about replication mechanisms.
The results (which I have recently submitted in a paper for publication) are interesting. To summarize, it seems very clear that regardless of what the unknown evolutionary mechanism might be, a smoothly continuous evolutionary path to high replication fidelity is impossible. At some point during the evolution of protolife to modern life, there had to be one or more major jumps (saltational events) in the degree of replication fidelity. We have a long way to go before we can get close to any idea of how life and evolution might have gotten started.
The Book of Works 
It must also be recognized that the mutation must be in the gamete cells or it will not pass on to the next generation. A question we had in a discussion one of my Biology classes was that since the mutation must occur in the reproductive cells for it to be passed on, the individual will not have the benefit, but the offspring might (yes “might”) get it. Without the “good” mutation providing an advantage, there is nothing to enhance the passing on of that variation.
I wonder if there is a mechanism in which certain types of stress result in lower fidelity?
Yes, there is. Its called “Error prone repair”. If a cell (bacteria) undegoes severe damage, the cell will switch to a repair system that makes more errors than normal. This increases the mutation rate (lowering fidelity) in the hope that some rare good mutation will arise, thus saving the whole population from extinctions. Desperate times call for desperate measures. Its a fascinating mechanism, and the research that uncovered it (I knew some of the folks) also fascinating.
Fascinating. I hadn’t really thought before about the likelihood of accurate replication. I really enjoyed reading this.
Thank you, Sheila
Yes, an interesting train of thought.
I’m no scientist, and know no detail about the reproductive process in bacteria, viruses and RNA, so I may be talking complete nonsense, but it occurs to me that there may have been a long period of time very early in the history of life or protolife on Earth when there was reproduction of a sort but a much lower rate of replication fidelity than was required to “fix” particular advantageous characteristics in a true- breeding species of organism. So a very primitive sort of single called organism might reproduce by fission and neither “offspring” be very like the “parent”. If they didn’t have, by inheritance or mutation, what it took to survive, and to produce offspring of their own, then then they wouldn’t, and that particular lineage would be no more, but then there has always been a vast amount of natural wastage. There were plenty more where they came from – not identical and not “breeding true” but still alive and still breeding. Life was continuing, even in a state of flux. And it seems to me that however it was technically achieved the characteristic that natural selection would most strongly act to preserve over the generations was faithful accurate replication, more strongly than any other characteristics however useful they were to their owner in promoting its own survival or its success in reproduction minus that accurate replication. Because alleles promoting more faithful replication are intrinsically more likely to get passed on than alleles that don’t have that result. Over time, in those early days, mutations from one generation to the next could occur at a very high level, some useful and some deleterious, but all likely to be impermanent over the generations. There would be no sort of species consistency at all. (And of course at that point in time there would be no sexual reproduction and no need therefore to find a physically compatible mate). But fidelity in replication, however different in other ways the bodies in which it found itself, would be a characteristic that WOULD tend to get passed on, with greater and greater regularity the higher the fidelity. Only when it reached a very high level would OTHER useful characteristics tend to be replicated too, and the evolution of species with consistent, replicable characteristics become possible.
Sally, that is indeed a very viable hypothesis, and in fact it provided the basis for my experimental simulations. I assumed an early (as you describe) state where cells have a low level of replication fidelity, and then ran a program to see what happens. That is the substance of the paper I just submitted. If it ever gets published, I will be discussing the surprising results in many venues.
But there is one part of your comment that I have not yet addressed. You say that increased replication fidelity would be a positive characteristic that would likely be passed down, or selected for. But why? Evolution does not plan ahead. It would only be a selective advantage if the increased fidelity produced an increase in fitness to the cell acquiring it, which may or may not always be the case. That aspect of the model how much does fidelity contribute to overall fitess must still be evaluated. Maybe next year.
Of course you are correct that evolution does not plan ahead. But that’s not what I was postulating. My point was quite different. Fidelity in replication (or whatever genetic material it is that bestows this characteristic) is of absolutely no selective advantage to the individual whose body contains this trait. It does not aid the individual to survive. It does not enable it to reproduce more often or in greater numbers either. But the trait DOES have selective advantage for ITSELF, compared with other traits. And that is all that is needed for it to be passed down to succeeding generations with ever greater frequency, along with the other traits that happen to share any given body with it. Bodies that don’t replicate with fidelity may reproduce, but many of their traits are lost in mutation. But a trait which promotes accurate replication has an increased chance of being accurately replicated, by its very nature, and crossing the generation gap intact.
Got it. Yes, you’re right. Thanks
Very interesting… However, I apologize for my limited understanding of the mechanisms of genetic “proofreading” and “error-correction”. Reading through this and then perusing a couple of academic articles for background information has left me with a number of probably ignorant questions:
How much does exchanging reproductive information between two members of a species (such as in, but not necessarily restricted to, sexual reproduction) affect the accumulation rate of mutations? What about the influence of viruses?
During replication, is the rate of fidelity the same in the leading and lagging strands? (A question elicited from the reading I did in order to follow your “My Favorite Enzyme” articles.) Is it thus possible that mutations also produce a “backup plan”, so to speak?
Sounds like this might be an at least partial explanation of the long period in the earth’s history antecedent to the development of multi-cellular life? Perhaps a replication fidelity of 99.99% was all that was achievable until some *fluke* mutation (per your response to Sally) resulted in a jump in the accuracy of replication. Or…
Maybe this is silly… Could it possibly have been the opposite case, that whatever early mechanism insured replication fidelity did so too exactly (and maybe also too slowly) to allow for much experimentation? How would a mutation-rate of 0.000001%, or perhaps even lower affect the evolution of something with a bacteria-like genome? In this case, “Heather Goodman Mashal’s” query might be of significance.
Kumi, great questions. I will try to answer them – in a couple of weeks. Traveling and deadlines until then. Thanks for your patience.
No worries… Good cheer to you, and please enjoy your travels (and deadlines)!
If fidelity in replication is a characteristic that needs to be at a certain ratio for “life to find a way” ..it would seem that organisms with an extremely high rate of fidelity would not have adapted much over time, and have been mostly extinct by now, thus leaving only organisms whose genomes demonstrate a lower amount of fidelity — and thus greater amount of adaptability — to population the earth by now.
Hey Sy, this is a really interesting read. I’d like to to reference it in my own upcoming blog on the origin of life (as an argument for God) if that’s ok.
Of course, Phillip. It would be an honor. Looking forward to reading your new book.