4 ms·

Sure, and that happens all the time in unicellular organisms. But it’s fundamentally different in multicellular organisms because they have distinct cells formi

by klmr 7y ago

Sure, and that happens all the time in unicellular organisms. But it’s fundamentally different in multicellular organisms because they have distinct cells forming the germ line. So any (random) changes to DNA in other cells won’t be transmitted. And while mutations in the germ line do happen, they are also random. So far there’s no known mechanism for systematic, guided DNA changes, and no good reason to assume that such mechanisms exist (on the contrary). Furthermore, the article is discussing epigenetic changes which, by definition, are not encoded in DNA and are instead transient (and thus not inherited trans-generationally).

blotter_paper 7y ago
> So far there’s no known mechanism for systematic, guided DNA changes, and no good reason to assume that such mechanisms exist (on the contrary). Why are we significantly less likely to have mutations on our mitochondria than in our fingers? It seems obvious to me that our DNA has error correction mechanisms, and some subsystems are more stringently error corrected than others. This amounts to a control on how much different aspects are allowed to deviate from the last generation. I would be incredibly surprised if a crocodile, who has been in a state of relative homeostasis for millions of years, has the same rate of mutation as a human. Note that I haven't suggested that a directional bias exists, just a set of mechanisms for changing variability of different traits. I wouldn't be particularly surprised by a mechanism for directional bias in some cases, but I don't assume there is one and I certainly don't feel comfortable making the case for it.
- klmr 7y ago
  > Why are we significantly less likely to have mutations on our mitochondria than in our fingers? I’m afraid this is simply not a biologically meaningful statement to begin with. Mitochondria are subcellular organelles. Fingers are complex organs that are formed from spatial arrangements of multiple cell types. Furthermore, mutations happen on the level of DNA, not on the level of either organelles or organs. Apart from that, mutation rate is (not quite, but more or less) uniform across the whole genome (the exceptions, due to e.g. GC bias, are not relevant here). Viable mutations are not uniformly distributed because of selection; that’s precisely the striking insight that Darwin had (though he was unaware of DNA and genes). Importantly, this does not require a guided error correction mechanism. Simply put, even slight variations in the oxidative phosphorylation pathway of the mitochondrion are likely to kill you during gestation; whereas similarly extreme variations in finger morphogenesis, at worst, make you unable to hold a tool. > some subsystems are more stringently error corrected than others This is virtually certainly not the case, because of what I’ve just described. Selection is sufficient to describe the outcome, and there is no evidence whatsoever to point to the mechanism you postulate. > I would be incredibly surprised if a crocodile, who has been in a state of relative homeostasis for millions of years, has the same rate of mutation as a human. Evolutionary mutation rate is governed by effective population size and generation time. That’s why fruit flies evolve fast and crocodiles evolve slowly. This, too, doesn’t require variable mutability of different traits, and no biologist has yet seriously suggested such a mechanism.
  - blotter_paper 7y ago
    > [...] Furthermore, mutations happen on the level of DNA, not on the level of either organelles or organs. This is all besides the point. Mitochondria are just an easy example because of the marked difference in mutation rate, and my loosely worded bit about fingers evolving should obviously be taken as "some parts of the genome associated with the development of fingers." > Apart from that, mutation rate is (not quite, but more or less) uniform across the whole genome (the exceptions, due to e.g. GC bias, are not relevant here). Not my field, but I'm pretty sure you're incorrect. Here's a citation: https://www.ncbi.nlm.nih.gov/pubmed/11057667?dopt=Abstract https://www.ncbi.nlm.nih.gov/pubmed/11057667?dopt=Abstract >> A few patterns have been found: proteins involved in antagonistic co-evolution (for example, immune genes, parasite antigens and reproductive conflict genes) tend to be rapidly evolving, and there is a correlation between the rate of protein evolution and the mutation rate of the gene. Here we report a new highly statistically significant predictor of a protein's rate of evolution, and show that linked genes have similar rates of protein evolution. >This is virtually certainly not the case, because of what I’ve just described. Selection is sufficient to describe the outcome, and there is no evidence whatsoever to point to the mechanism you postulate. This is virtually certainly not the case, because of what I've just cited. > Evolutionary mutation rate is governed by effective population size and generation time. I'm not arguing that these aren't factors, but we do have good reason to believe that the rate of change for some subsets of the genome can itself change. Here's another source: https://www.ncbi.nlm.nih.gov/pubmed/10469563?dopt=Abstract https://www.ncbi.nlm.nih.gov/pubmed/10469563?dopt=Abstract >> Our results provide the first substantial statistical evidence for the existence of a regional variation in the synonymous substitution rate within the mammalian genome, indicating that different chromosomal regions evolve at different rates. This regional phenomenon which shapes gene evolution could reflect the existence of 'evolutionary rate units' along the chromosome.
    - klmr 7y ago
      You fundamentally misunderstand the article you cite. It describes population-level events, and it’s entirely compatible with what I’ve said: variable mutation rates, in modern evolutionary biology, are entirely explained by variable selective pressure (see “purifying selection”, which is what I’ve described in my previous comment using your example). As for the second article, I’ve made reference to that in my previous comment, too (that’s GC bias). And, as mentioned, this isn’t relevant here.
cbkeller 7y ago
> and thus not inherited trans-generationally I'm not sure what you're referring to here? There appears to be quite a significant body of literature on epigenetic inheritance -- just to pick a few: [1,2,3,4]. The term "Transgenerational epigenetic inheritance" even has its own wikipedia page: https://en.wikipedia.org/wiki/Transgenerational_epigenetic_inheritance https://en.wikipedia.org/wiki/Transgenerational_epigenetic_i... [1] https://www.nature.com/articles/ng1199_314 https://www.nature.com/articles/ng1199_314 [2] https://www.nature.com/articles/nrg1834 https://www.nature.com/articles/nrg1834 [3] https://www.nature.com/articles/nature05917 https://www.nature.com/articles/nature05917 [4] https://doi.org/10.1016/j.cell.2014.02.045 https://doi.org/10.1016/j.cell.2014.02.045
- deleted 7y ago
  [deleted]
- klmr 7y ago
  Yes, I’m well aware of TEI, it being my former field of research. However, as your link (4) shows there are all kinds of caveats, and usual epigenetic inheritance isn’t transgenerational (in fact, it’s a ubiquitous, “mundane” biological mechanism to maintain cellular state). Your first example — agouti mouse coat colour — is essentially the only firmly established example of TEI in mammals. And, as I explained in another comment, TEI tends to attenuate over generations, and it probably functions very differently in non-mammalian organisms. To date, the existence of pervasive TEI in mammals remains a point of contention. Outside of the agouti locus there’s almost no high-quality, replicated evidence for its existence, and the hypothesis is fundamentally hindered by the lack of a plausible mechanism [1]. Most epigenetics research focuses on other things, and there’s general scepticism that TEI in mammals is all that important [2]. [1] https://www.theguardian.com/science/sifting-the-evidence/2016/mar/02/rats-epigenetics-maybe-our-great-grandmothers-arent-responsible-for-our-alcoholism-after-all https://www.theguardian.com/science/sifting-the-evidence/201... [2] https://twitter.com/ewanbirney/status/1014494822525296640 https://twitter.com/ewanbirney/status/1014494822525296640
  - cbkeller 7y ago
    Ok, thanks for clarifying! Is that part of why you got out of the field?

by klmr 7y ago

blotter_paper 7y ago

> So far there’s no known mechanism for systematic, guided DNA changes, and no good reason to assume that such mechanisms exist (on the contrary). Why are we significantly less likely to have mutations on our mitochondria than in our fingers? It seems obvious to me that our DNA has error correction mechanisms, and some subsystems are more stringently error corrected than others. This amounts to a control on how much different aspects are allowed to deviate from the last generation. I would be incredibly surprised if a crocodile, who has been in a state of relative homeostasis for millions of years, has the same rate of mutation as a human. Note that I haven't suggested that a directional bias exists, just a set of mechanisms for changing variability of different traits. I wouldn't be particularly surprised by a mechanism for directional bias in some cases, but I don't assume there is one and I certainly don't feel comfortable making the case for it.

klmr 7y ago
> Why are we significantly less likely to have mutations on our mitochondria than in our fingers? I’m afraid this is simply not a biologically meaningful statement to begin with. Mitochondria are subcellular organelles. Fingers are complex organs that are formed from spatial arrangements of multiple cell types. Furthermore, mutations happen on the level of DNA, not on the level of either organelles or organs. Apart from that, mutation rate is (not quite, but more or less) uniform across the whole genome (the exceptions, due to e.g. GC bias, are not relevant here). Viable mutations are not uniformly distributed because of selection; that’s precisely the striking insight that Darwin had (though he was unaware of DNA and genes). Importantly, this does not require a guided error correction mechanism. Simply put, even slight variations in the oxidative phosphorylation pathway of the mitochondrion are likely to kill you during gestation; whereas similarly extreme variations in finger morphogenesis, at worst, make you unable to hold a tool. > some subsystems are more stringently error corrected than others This is virtually certainly not the case, because of what I’ve just described. Selection is sufficient to describe the outcome, and there is no evidence whatsoever to point to the mechanism you postulate. > I would be incredibly surprised if a crocodile, who has been in a state of relative homeostasis for millions of years, has the same rate of mutation as a human. Evolutionary mutation rate is governed by effective population size and generation time. That’s why fruit flies evolve fast and crocodiles evolve slowly. This, too, doesn’t require variable mutability of different traits, and no biologist has yet seriously suggested such a mechanism.
- blotter_paper 7y ago
  > [...] Furthermore, mutations happen on the level of DNA, not on the level of either organelles or organs. This is all besides the point. Mitochondria are just an easy example because of the marked difference in mutation rate, and my loosely worded bit about fingers evolving should obviously be taken as "some parts of the genome associated with the development of fingers." > Apart from that, mutation rate is (not quite, but more or less) uniform across the whole genome (the exceptions, due to e.g. GC bias, are not relevant here). Not my field, but I'm pretty sure you're incorrect. Here's a citation: https://www.ncbi.nlm.nih.gov/pubmed/11057667?dopt=Abstract https://www.ncbi.nlm.nih.gov/pubmed/11057667?dopt=Abstract >> A few patterns have been found: proteins involved in antagonistic co-evolution (for example, immune genes, parasite antigens and reproductive conflict genes) tend to be rapidly evolving, and there is a correlation between the rate of protein evolution and the mutation rate of the gene. Here we report a new highly statistically significant predictor of a protein's rate of evolution, and show that linked genes have similar rates of protein evolution. >This is virtually certainly not the case, because of what I’ve just described. Selection is sufficient to describe the outcome, and there is no evidence whatsoever to point to the mechanism you postulate. This is virtually certainly not the case, because of what I've just cited. > Evolutionary mutation rate is governed by effective population size and generation time. I'm not arguing that these aren't factors, but we do have good reason to believe that the rate of change for some subsets of the genome can itself change. Here's another source: https://www.ncbi.nlm.nih.gov/pubmed/10469563?dopt=Abstract https://www.ncbi.nlm.nih.gov/pubmed/10469563?dopt=Abstract >> Our results provide the first substantial statistical evidence for the existence of a regional variation in the synonymous substitution rate within the mammalian genome, indicating that different chromosomal regions evolve at different rates. This regional phenomenon which shapes gene evolution could reflect the existence of 'evolutionary rate units' along the chromosome.
  - klmr 7y ago
    You fundamentally misunderstand the article you cite. It describes population-level events, and it’s entirely compatible with what I’ve said: variable mutation rates, in modern evolutionary biology, are entirely explained by variable selective pressure (see “purifying selection”, which is what I’ve described in my previous comment using your example). As for the second article, I’ve made reference to that in my previous comment, too (that’s GC bias). And, as mentioned, this isn’t relevant here.

cbkeller 7y ago

> and thus not inherited trans-generationally I'm not sure what you're referring to here? There appears to be quite a significant body of literature on epigenetic inheritance -- just to pick a few: [1,2,3,4]. The term "Transgenerational epigenetic inheritance" even has its own wikipedia page: https://en.wikipedia.org/wiki/Transgenerational_epigenetic_inheritance https://en.wikipedia.org/wiki/Transgenerational_epigenetic_i... [1] https://www.nature.com/articles/ng1199_314 https://www.nature.com/articles/ng1199_314 [2] https://www.nature.com/articles/nrg1834 https://www.nature.com/articles/nrg1834 [3] https://www.nature.com/articles/nature05917 https://www.nature.com/articles/nature05917 [4] https://doi.org/10.1016/j.cell.2014.02.045 https://doi.org/10.1016/j.cell.2014.02.045

deleted 7y ago
[deleted]
klmr 7y ago
Yes, I’m well aware of TEI, it being my former field of research. However, as your link (4) shows there are all kinds of caveats, and usual epigenetic inheritance isn’t transgenerational (in fact, it’s a ubiquitous, “mundane” biological mechanism to maintain cellular state). Your first example — agouti mouse coat colour — is essentially the only firmly established example of TEI in mammals. And, as I explained in another comment, TEI tends to attenuate over generations, and it probably functions very differently in non-mammalian organisms. To date, the existence of pervasive TEI in mammals remains a point of contention. Outside of the agouti locus there’s almost no high-quality, replicated evidence for its existence, and the hypothesis is fundamentally hindered by the lack of a plausible mechanism [1]. Most epigenetics research focuses on other things, and there’s general scepticism that TEI in mammals is all that important [2]. [1] https://www.theguardian.com/science/sifting-the-evidence/2016/mar/02/rats-epigenetics-maybe-our-great-grandmothers-arent-responsible-for-our-alcoholism-after-all https://www.theguardian.com/science/sifting-the-evidence/201... [2] https://twitter.com/ewanbirney/status/1014494822525296640 https://twitter.com/ewanbirney/status/1014494822525296640
- cbkeller 7y ago
  Ok, thanks for clarifying! Is that part of why you got out of the field?