We know that the DNA copying mechanism that replicates DNA during cellular division is not 100% accurate and the resultant errors are the source of variation in the members of a population.

At the same time, we are also aware of the benefits of variation - how it is useful in ensuring the survival of a species over time and leading to evolution.

I would however like to know if 100% accurate DNA replication is possible (even if hypothetically) - because in my opinion, organisms can surely survive (atleast individually) without variation or evolution.

If it is so, is it possible that organisms with 100% accurate DNA replication did exist, but eventually their populations died out (due to natural selection) and we were left only with organisms that showed variation?

Putting in simpler terms, it is possible that evolution itself is the cause of variation that now causes further evolution?

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    $\begingroup$ Related: biology.stackexchange.com/questions/378/… $\endgroup$ – Bryan Krause Sep 8 '19 at 14:37
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    $\begingroup$ For your question about whether 100% accurate replication is possible, think carefully about multicellular organisms. Any evolutionary benefit to mutation would have to be in the germ cells. For non-germ cells, you (in most cases) want as little variation as possible since that variation will never been heritable. $\endgroup$ – Bryan Krause Sep 8 '19 at 14:42
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    $\begingroup$ There are many kinds of DNA replication errors that lead to mutations some of them could be 100% error free some are inherently not possible. $\endgroup$ – Cell Sep 8 '19 at 15:28
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    $\begingroup$ @MrigankPawagi I'm trying to steer you towards a more answerable, non-hypothetical question. If 100% error free replication is possible, we'd have something like it in somatic cells. If allowing errors in germ cells is beneficial, we'd expect higher error rates in germ cells. $\endgroup$ – Bryan Krause Sep 8 '19 at 16:48
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    $\begingroup$ If you go to the Tour, you will read: "Focus on questions about an actual problem you have faced. Include details about what you have tried and exactly what you are trying to do. Ask about... general questions about biological concepts, questions about the biological mechanisms behind medical conditions, questions about techniques in a biological or biochemical laboratory". And "Not all questions work well in our format. Avoid questions that are primarily opinion-based, or that are likely to generate discussion rather than answers." $\endgroup$ – David Sep 8 '19 at 17:09

You're asking if cells arose with 100% replication accuracy and if lower accuracy was selected for under a feedback loop. Maybe there was a sweet spot for DNA replication accuracy in terms of efficiency, but it's highly unlikely that our ancestor cells had 100% fidelity in DNA replication because if we look at yeast for example, there are many genes dedicated to different types of post-replication repair including mismatch repair, base excision repair, and translesion synthesis. All of these can lead to mutations if they aren't working properly and some (translesion synthesis) inherently generate mutations. It doesn't seem consistent for a cell to develop all of these sophisticated post-replication repair systems to protect itself from DNA damage and then to give some more leeway to DNA replication because it was just too accurate.

Also there are papers like this that talk about how E. coli have increase mutation rates under stress. But if your hypothesis was true, then E. coli would ideally have 100% replication fidelity under normal conditions and lower it when stressed, or they would just have a higher baseline mutation frequency all the time. But, neither of these is observed. What makes the most sense when all this information is put together is that cells try to have as high DNA replication fidelity as possible under ideal conditions.

As per your other question, maybe it's possible to have a 100% accurate DNA polymerase NEB engineers high fidelity polymerases for lab use maybe someday it can reach 0 errors. But there are other sources of mutations like the spontaneous deamination of cytosine that can generate mutations during replication, but that depends on the chemical properties of cytosine so it's not really fixable unless you use different nucleobases.


Mutation as a Stress Response and the Regulation of Evolvability. (2012)

By: Rodrigo S. Galhardo, P. J. Hastings, and Susan M. Rosenberg

  • $\begingroup$ Great answer. I have read about E. Coli and I am totally convinced with your point about the post-replication repair in yeast. $\endgroup$ – Mrigank Pawagi Sep 9 '19 at 17:23

There is previous research for that field of macroevolution.... Horse shoe crabs change slowly and tropical fish change fast.

You are right, it's not just random variation, it's fine tuned by DNA transcription processes which are too developed to be random, so the complexity of the processes leads scientists to think "WTF" regarding epigenetics, transgenerational phenotypic plasticity, paramutation, genetic drift, DNA mutation types, Specifically: "no systematic cross species studies of variation have been conducted (most focus on model organisms)", because the topic is so intense.

You don't have to change the DNA code of alleles to go from a chimpanzee to a human, most of the changes come from pre-existing genes that are varied to produce different results.

The texts for macroevolution fine-tuning of variability talk about: variability, gene flow, constriction, epigenetics, of traits of adaptive significance, of DNA mutations, their mathematical measurement... it can be summarized by this statement:

" variability has been a dilemma of evolutionary biology. Considering the pattern of increased genetic variation associated with environmental clines and heterogeneous environments, selection in heterogeneous environments has been proposed to facilitate the maintenance of genetic variation. No comprehensive models have been developed, likely due to the genetic and environmental complexity of this issue. " ref

Many books are devoted to the subject, so there is lots to read through, and there are mutation-control systems that fine tune variability, so it gets complex:

"... Epigenetic modifications, such as; DNA methylation, together with covalent modification of histones, are thought to alter chromatin density and accessibility of the DNA to cellular machinery, thereby modulating the transcriptional potential of the underlying DNA sequence" ref

There are genetic switches, which vary which DNA sequences are expressed by different species... Humans and chimps are 98% the same, and genetic switches can change the species selectively without having to change the DNA itself... "regulates when and where genes are turned on and off and how much protein they produce. The regulatory machinery works when proteins called transcription factors bind to specific short sequences of DNA that flank the gene, called transcription factor binding sites, and by doing so, switch genes on and off." ref

sharks ahve less less variability than humans and 1.5 times bigger genome... "The researchers found that the white shark genome contained a lot of genes responsible for maintaining genetic stability — things like DNA-repair genes and tumor-suppressing genes. And when the researchers compared the white shark's stability genes with analogous genes in other vertebrates, they found small changes in the gene sequence that suggest a specific pattern of evolutionary adaptation for these genes in white sharks."

Only a few epigenetic processes for transgenerational epigenetic inheritance have been discovered, which vary species traits independently of the DNA sequence, so we don't even know how they compare between animal families.

  • $\begingroup$ Interesting Answer indeed. I would suggest reading Cell's argument about yeast as well (on his answer) $\endgroup$ – Mrigank Pawagi Sep 9 '19 at 17:24

In short, no evolution is not a result of variation. Evolution is a process in which each population in a system compete for a limited number of resources and each population has a fitness score (how well suited for the environment they are, this score is a man made concept to help illustrate the point), the populations with a higher fitness score tend to outcompete other species and so they are more likely to survive. This process occurs on a more individualistic level too, individuals in a population can be given a fitness score and individuals with a higher fitness score are more likely to survive and reproduce. Fitness scores are altered by mutations in individuals which may enhance/reduce the function of a certain behaviour/reaction that is required for survival. More advantageous mutations are inherited more often and so accrue within a population and thus over time the fitness score of a population increases too. Mutations are fairly random (they have a higher frequency at certain locations, but it is generally random) and they often occur due to the inherent instability of the bases present in nucleotides. These mutations thus result in the gradual changing of genomes throughout a population, leading to subsequent changes in phenotype - evolution. With regards to whether an organism ever had 100% accurate copying mechanism, the answer is no again. It is not possible for an organism to achieve this level of fidelity to the nature of the bases used in organism. The DNA bases are inherently unstable due to tautomerisms, deaminations... they can also be altered by natural external factors such as UV radiation which base dimerisation as the electrons in the rings are excited and form new bonds. Although cells have repair mechanisms, these are not 100% efficient as tuatomersiation can occur when the base is in the active site of the polymerase, alternatively, the mutation may occur in a very crowded region in the nucleus, limiting the ability of repair machinery to encounter the DNA by diffusion. Finally, cells are often unable to recognise foreign DNA that has been integrated into their genomes, which will also cause mutations. Although polymerases have and will continue to undergo extensive rounds of directed evolution it will be almost impossible to produce a polymerase with 100% fidelity unless the bases themselves are changed to being pretty much inert with a ridiculously high stability (remember there are millions/billions of bases in a cell so even if the mutation rate is low there will likely still be some mutations). In response to Mrigank in the comments (my answer was too long for a comment :/) yeah pretty much Now it may be possible that we can develop polymerases through directed evolution to have even higher fidelity (although this may be difficult as it could slow down the catalytic rate and then implementstion is alsonhard) and to improve the DNA repair pathways through directed evolution but the bases are inately unstable and there is always some chance of them converting through processes such as tautomerism. Additionally, b cells use a process called somatic hypermutation to actively mutate the DNA of b cell receptors/antibodies for affinity maturation in the dark zone so if we had a system that did not allow for variation there we may have a weakened immune system. Additionally, some repair pathways such as non homoogous end joining don't faithfully repair the DNA they just quickly repair double stranded breaks which can be lethal and this process can result in insertions and deletions. Then at the level of meiosis, since nobody has exactly the same genome and the child gets a chromosome from each parent variation is generated there. Things like viral integration, damage from external mutagens and free radical attack also occur which all lead to mutations. So I don't think it's possible for DNA polymerase to replicate DNA with 100% fidelity and I don't think it's possible in a looser sense for the DNA sequence to not change, hence variation is inevitable.

  • $\begingroup$ Thanks fo the direct Answer. So that means DNA can naturally never be replicated 100% accurately and hence variation is inevitable. $\endgroup$ – Mrigank Pawagi Sep 11 '19 at 0:50
  • $\begingroup$ Please see the edited answer $\endgroup$ – pepsiandsoda Sep 11 '19 at 8:58

Is variation a result of Evolution?

No, you're putting the cart before the horse & mistaking cause for effect.

Variation is the result of mutation (whether caused by copying errors, radiation or whatever).

Evolution is the result of variation.

Mutation > Variation > Evolution

Evolution is merely the winnowing process by which more beneficial variations (as in terms of fittest to survive in the existing environment, which includes competition from other variations) 'succeed' & less beneficial ones don't, it doesn't cause the variations.

Variation can happen without evolution but evolution can't happen without variation.


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