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GC content (the local ratio of G and C nucleotides, i.e. (#C + #G) / (#A + #C + #G + #T)) varies in patches across certain mammalian genomes. GC content correla

by klmr 7y ago

GC content (the local ratio of G and C nucleotides, i.e. (#C + #G) / (#A + #C + #G + #T)) varies in patches across certain mammalian genomes. GC content correlates with stability because stacked C–G base pairs are chemically more stable than A–T base pairs. However, while gene density correlates with GC content, gene function is uncorrelated. This means that genes (which tend to be in high-GC regions) in general tend to be (very, very slightly) less susceptible to mutations than non-genic DNA (by contrast, they are vastly less susceptible to mutation than non-genic DNA due to negative selection^1). But the difference in GC content between different genes is purely stochastic, and there’s no mechanism for changing the GC content of a given gene, except by random (!) mutation. This can happen, and it indeed improves the stability of a gene, but the same is true for all genes to the same extent, and it isn’t directed. ^1 I’ve never seen anybody explicitly quantify this but the relative impact of GC content and negative selection on mutation rate must be several orders of magnitude different … at a guess at least thousandfold, more likely millionfold.

blotter_paper 7y ago
> But the difference in GC content between different genes is purely stochastic, and there’s no mechanism for changing the GC content of a given gene, except by random (!) mutation. This can happen, and it indeed improves the stability of a gene, but the same is true for all genes to the same extent, and it isn’t directed. That seems fine. If some genes are more stable than others, and this can vary by normal random mutation, it can be selected for. I'm still failing to see why this isn't relevant to the current discussion.
- klmr 7y ago
  Because it’s just stochastic. There’s no mechanism for systematic, guided DNA changes to mutate some genes more than others, which is exactly what I wrote in my initial comment that you took umbrage at. “It can be selected” for only through the blind process of chance, which isn’t really selection at all.
  - blotter_paper 7y ago
    > “It can be selected” for only through the blind process of chance, which isn’t really selection at all. Selecting is not blind, selecting is sexual or based on survival. The mutation that changes the rate of other mutations is random, but once that mutation occurs it can be selected for via normal means.
    - klmr 7y ago
      Iʼm aware of how evolution works, thanks. I do have a PhD in genetics after all. But this isnʼt what you were talking about here, which is the hypothetical existence of a biological mechanism enacting differential, directional selection. Evolutionary selection (regardless of whether natural, sexual, artificial or whatever) happens in aggregate over multiple generations, it canʼt account for guided mutations in the germ line that encode “learned” behaviour (which, as my initial comment explained, simply donʼt exist).
      - blotter_paper 7y ago
        I appreciate that you are more well versed in your field than I am. That doesn't mean that you're not making a misstep here. I've known some PhDs and while they often have good points to make in their fields I've also seen some of them eat crow more than once. We're all human. > But this isnʼt what you were talking about here, which is the hypothetical existence of a biological mechanism enacting differential, directional selection. It should be noted that I never said directional -- I actually made it explicitly clear in my first post that I was not arguing for a direction, only for modified rates of change: "Note that I haven't suggested that a directional bias exists, just a set of mechanisms for changing variability of different traits." So, I think this is what I've been talking about from the beginning. Perhaps it's due to my lack of familiarity with domain specific language, but I'm not sure that you're understanding what I've been arguing for. Please don't get bogged down in the specifics of this example (it's the pointing finger, not the moon), but I'm not suggesting that cheetahs evolved a tendency to evolve faster running, I'm suggesting that they might have had a period of evolution where a variety of genes related to running were more likely to change in both beneficial and non-beneficial ways, but because faster running was such a beneficial trait it actually made sense for some portion of the population to have offspring who were more likely to have both beneficial and harmful changes happen over the relevant sections of genetic code. In times of less rapid environmental/adversarial change, where stagnation is good enough and the reward for beneficial deviation is more outweighed by the risk of harmful deviation, the rate of change can be toggled back down (again through normal evolution). 1) Do we agree that random mutations of the germline can result in differing rates of change across subsets of the genome? 2) Do we agree that this can affect the viability of offspring? 3) If yes to both of the above, is any component missing for evolution to select for different rates of variability in different subsets of the genome?

by klmr 7y ago

blotter_paper 7y ago

> But the difference in GC content between different genes is purely stochastic, and there’s no mechanism for changing the GC content of a given gene, except by random (!) mutation. This can happen, and it indeed improves the stability of a gene, but the same is true for all genes to the same extent, and it isn’t directed. That seems fine. If some genes are more stable than others, and this can vary by normal random mutation, it can be selected for. I'm still failing to see why this isn't relevant to the current discussion.

klmr 7y ago
Because it’s just stochastic. There’s no mechanism for systematic, guided DNA changes to mutate some genes more than others, which is exactly what I wrote in my initial comment that you took umbrage at. “It can be selected” for only through the blind process of chance, which isn’t really selection at all.
- blotter_paper 7y ago
  > “It can be selected” for only through the blind process of chance, which isn’t really selection at all. Selecting is not blind, selecting is sexual or based on survival. The mutation that changes the rate of other mutations is random, but once that mutation occurs it can be selected for via normal means.
  - klmr 7y ago
    Iʼm aware of how evolution works, thanks. I do have a PhD in genetics after all. But this isnʼt what you were talking about here, which is the hypothetical existence of a biological mechanism enacting differential, directional selection. Evolutionary selection (regardless of whether natural, sexual, artificial or whatever) happens in aggregate over multiple generations, it canʼt account for guided mutations in the germ line that encode “learned” behaviour (which, as my initial comment explained, simply donʼt exist).
    - blotter_paper 7y ago
      I appreciate that you are more well versed in your field than I am. That doesn't mean that you're not making a misstep here. I've known some PhDs and while they often have good points to make in their fields I've also seen some of them eat crow more than once. We're all human. > But this isnʼt what you were talking about here, which is the hypothetical existence of a biological mechanism enacting differential, directional selection. It should be noted that I never said directional -- I actually made it explicitly clear in my first post that I was not arguing for a direction, only for modified rates of change: "Note that I haven't suggested that a directional bias exists, just a set of mechanisms for changing variability of different traits." So, I think this is what I've been talking about from the beginning. Perhaps it's due to my lack of familiarity with domain specific language, but I'm not sure that you're understanding what I've been arguing for. Please don't get bogged down in the specifics of this example (it's the pointing finger, not the moon), but I'm not suggesting that cheetahs evolved a tendency to evolve faster running, I'm suggesting that they might have had a period of evolution where a variety of genes related to running were more likely to change in both beneficial and non-beneficial ways, but because faster running was such a beneficial trait it actually made sense for some portion of the population to have offspring who were more likely to have both beneficial and harmful changes happen over the relevant sections of genetic code. In times of less rapid environmental/adversarial change, where stagnation is good enough and the reward for beneficial deviation is more outweighed by the risk of harmful deviation, the rate of change can be toggled back down (again through normal evolution). 1) Do we agree that random mutations of the germline can result in differing rates of change across subsets of the genome? 2) Do we agree that this can affect the viability of offspring? 3) If yes to both of the above, is any component missing for evolution to select for different rates of variability in different subsets of the genome?