Biophysics Cell biology Conservation of Information Darwinism Entropy extinction Genetics Informatics Intelligent Design Natural selection

Would greater DNA harm enhance evolution or degradation?

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Mutations are used to explain evolution but also cause cancer. Biologists have discovered conditions for multiple mutations. Can we therefore infer that evolution via mutations is more likely? or that enhanced mutations will cause faster species degradation and extinction?

Biologists describe mechanism promoting multiple DNA mutations

DNA mutations—long known to fuel cancer as well as evolutionary changes in a living organism—had been thought to be rare events that occur randomly throughout the genome.

However, recent studies have shown that cancer development frequently involves the formation of multiple mutations that arise simultaneously and in close proximity to each other. . . .Anna Malkova, associate professor of biology in the UI College of Liberal Arts and Sciences, notes that the DNA repair pathway, known as break-induced replication (BIR), can promote clusters of DNA mutations.

“Previously, we have shown that double-strand DNA breaks, which can result from oxidation, ionizing radiation and replication errors, can be repaired by BIR,” says Malkova.

“During BIR, one broken DNA end is paired with an identical DNA sequence on another chromosome and initiates an unusual type of replication, which proceeds as a migrating bubble and is associated with the accumulation of large amounts of single-strand DNA,” she says.

In the Cell Reports study, researchers subjected yeast cells undergoing BIR to alkylating (cancer cell-killing agents) damage. “We found that the single-stranded DNA regions that accumulate during BIR are susceptible to damage that leads to the formation of mutation clusters,” explains Cynthia Sakofsky, postdoctoral fellow at the UI and one of two co-first authors on the paper. “These clusters are similar to those found in human cancer,” she says.

Importantly, say the researchers, the paper provides a mechanism to potentially explain how genetic changes form in human cancers. Thus, it will be critical for future research to determine whether BIR can form clustered mutations that lead to cancer in humans.

Paper: Break-induced replication is a source of mutation clusters underlying kataegis.
Sakofsky et al. Cell Rep. 2014 Jun 12;7(5):1640-8. doi: 10.1016/j.celrep.2014.04.053. Epub 2014 May 29.
Abstract

Clusters of simultaneous multiple mutations can be a source of rapid change during carcinogenesis and evolution. Such mutation clusters have been recently shown to originate from DNA damage within long single-stranded DNA (ssDNA) formed at resected double-strand breaks and dysfunctional replication forks. Here, we identify double-strand break (DSB)-induced replication (BIR) as another powerful source of mutation clusters that formed in nearly half of wild-type yeast cells undergoing BIR in the presence of alkylating damage. Clustered mutations were primarily formed along the track of DNA synthesis and were frequently associated with additional breakage and rearrangements. Moreover, the base specificity, strand coordination, and strand bias of the mutation spectrum were consistent with mutations arising from damage in persistent ssDNA stretches within unconventional replication intermediates. Altogether, these features closely resemble kataegic events in cancers, suggesting that replication intermediates during BIR may be the most prominent source of mutation clusters across species.

7 Replies to “Would greater DNA harm enhance evolution or degradation?

  1. 1
    Mung says:

    Does the book Genetic Entropy linked in the OP establish that the genome of any living species can’t be more than 6,000 years old?

    Does it establish that any species has ever gone extinct due to “genetic entropy”?

  2. 2
    Gordon Davisson says:

    In this case, as in many others, the dose makes the poison. For example, oxygen is necessary for human life, and in some cases a higher concentration of oxygen can be helpful, but if the concentration is too high it becomes toxic. Water is similar: keeping well hydrated is good, too much is toxic. The same is true of a wide variety of nutrients (vitamins, essential elements, … salt, caloric intake, etc).

    Anyway, the point is that just because a bit of something is good (or even essential) does not mean that more of it will be even better. And that’s the case with mutations in evolution. The simple explanation is that increasing the mutation rate increases the occurrence of both beneficial and deleterious mutations; selection (mostly) removes the deleterious mutations, but it has a limited capacity to do so (a bit over one bad mutation per individual, although it can vary quite a bit depending on the details).

    Increasing the mutation rate up to the limit where selection can keep up with the rate of new deleterious mutations increases the rate at which beneficial mutations can accumulate. Increasing it beyond that limit would make deleterious mutations accumulate in the population, which would overwhelm the effect the beneficial mutations would have.

    This would be roughly the “genetic entropy” scenario Dr. Sanford envisions. But while there is some evidence that the deleterious mutation rate in humans exceeds that limit, the case that there’s a problem doesn’t seem very solid to me. It’s certainly not as overwhelming and obvious as Dr. Sanford assumes.

  3. 3
    Mung says:

    nice analogy. Seems we have here yet another case of fine-tuning. 🙂

    Setting aside visions of biochemical disaster, is there any informational reason for limiting mutation rates?

  4. 4
    wd400 says:

    Dunno, but there’s very nice evolutionary explanation for the values of mutation rates: the mutation rate of a lineage is as low as effective population size (and therefore strength of selection) allows it to be:

    http://www.pnas.org/content/109/45/18488.full

  5. 5
    Gordon Davisson says:

    Mung: “Seems we have here yet another case of fine-tuning.”

    Maybe; the article I cited assumes at least common ancestry between humans and chimps, and while I haven’t read the one wd400 cited, I’m pretty sure it (and the other articles it references) all assume evolution is basically correct. So if you’re a young-life creationist, there’s no reason to expect their conclusions to correspond to reality. OTOH, if you’re a believer in front-loaded ID, or guided mutations, or a rigged fitness function (“active information” as in the NFLT argument), or… then the results are much more relevant.

    BTW, please allow me a mini-rant here: I’ve thought for a long time that the current design-centric/design detection approach to ID is crippling it. If ID is ever to have a chance of competing head-to-head with evolution as a theory of how life came to be the way it is, then ID will have to propose, evaluate, and test various possibilities for how life came to be the way it is. The best it can offer within the design-centric paradigm is that an intelligent designer was involved somehow, and that simply doesn’t give much basis for making testable predictions. The science is in the details, and design-centric ID stays too far away from the details.

    So let me take a look at how this bit of (possible) fine-tuning fits with various possible variants of ID. Suppose, for example, we went with an ID via recent creation hypothesis: then I’d (at least intuitively) expect the mutation rate to either be set very low (“I created life the way I wanted it; why would I design it to fall apart?”) or much higher than the sustainable rate (because it’s not expected to last long anyway, so why design it to hold up past its expected lifetime?). Anyway, under this hypothesis a mutation rate tuned for evolution doesn’t make much sense.

    Under a front-loading or rigged-fitness-function hypothesis, the tuning makes perfect sense. In either of these cases, we expect the mechanisms wd400 mentioned to tune it in exactly the same way it would under unassisted evolution.

    Under a guided-mutation hypothesis… it looks a bit complicated, depending on exactly how guided the mutations are. In the extreme case, where all mutations are guided, wouldn’t we expect to see no deleterious mutations at all? OTOH with the hypothesis that just a few designed mutations are added (in addition to the spontaneous ones), I’d expect a designer to pull the level of spontaneous mutation down, and then inject the desired mutations “by hand”.

    So it looks to me like this form of fine-tuning is consistent with unassisted evolution and some ID hypotheses, but problematic for other ID hypotheses (and under some ID hypotheses may not exist at all).

  6. 6
    Mung says:

    Hi Gordon,

    I’m not a young-earth creationist, or, as you put it, a young-life creationist. I’m also not a fan of front-loading. I will however say that I am a theist, and a Christian.

    I’ll permit you your mini-rant. 🙂

    For sure ID is in a rather tenuous position, especially with regard to it’s status as science. I would not agree that ID must put forth testable claims of how the designer did it (iow, how life came to be the way it is). But I would be willing to grant that if it is not putting forth fruitful avenues of research that it will probably not flourish as a scientific endeavor.

    Of course, most of us here at UD in favor of ID are still trying to get past the “could ID even be science” barrier.

    The point of my post was to raise the question of whether we can consider certain aspects of the evolutionary process to be a communication problem, and then to see what would be consistent with that view.

    So, for example, within the cell we have the transcription of DNA into RNA and the translation from RNA into a polypeptide.

    How does the cell convert DNA into working proteins? The process of translation can be seen as the decoding of instructions for making proteins, involving mRNA in transcription as well as tRNA.

    here

    What role would mutations play in this process, from a communications point of view? Would they be considered to be noise?

    Then further, consider heredity and what it might require to persist a genome that can result in a viable organism over multiple generations. In another thread you mentioned the copying process (in the context of entropy).

    How ought we to consider mutations? Why do organisms appear to “resist” them? Are they noise? Or are they the engine of evolution?

    By analogy, say I am trying to teach you the fundamentals of thermodynamics (yes, laughable). Will you somehow learn more information by random changes to the text? (Well, in this case, I grant that you might!)

    Then, finally, consider what it even requires in the first place to establish such a communications system that is resistant to perturbations. What a remarkable coincidence!

  7. 7
    Mung says:

    p.s. The whole fine-tuning thing can be left aside (for now).

    I am most interested in your thoughts on whether communication theory can be applied to biological processes, and if so, what is the role of mutations.

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