wgscott Posted January 4, 2017 Share Posted January 4, 2017 But folks who know anything rather than inaccurately tossing words around know regulatory DNA ain't junk. They also know "a lot" is a very relative term, and that all non-junk, including regulatory sequences, amounts to ~9% of the human genome. I hope I am reading this in a different way than was intended, but if not, you are more than welcome to teach my class for me next fall. Meanwhile, https://www.theguardian.com/science/2012/sep/05/genes-genome-junk-dna-encode Link to comment
Jud Posted January 4, 2017 Author Share Posted January 4, 2017 I hope I am reading this in a different way than was intended, but if not, you are more than welcome to teach my class for me next fall. Meanwhile, https://www.theguardian.com/science/2012/sep/05/genes-genome-junk-dna-encode Apologies for the tone, which you're correct was unintended. Regarding regulatory DNA not being junk, it was a meme in the popular science press (at least - some journal articles, perhaps?) that all DNA that didn't code for proteins was considered "junk," but I'm not aware of any reputable scientist working in the field who took the position that regulatory DNA was junk. I'm sure you're aware of the rise of "evo-devo," which pays a tremendous amount of attention to regulatory DNA and the role it has played in evolution. Regarding ENCODE, they used a definition of "function" that considered a sequence functional if it had biological activity, e.g., if it was transcribed. There was no requirement that the transcript do anything at all, so for instance ERV (endogenous retrovirus) sequences that are pervasively transcribed (because that's what virus DNA does, even after it's been absorbed into the human genome) was counted as functional. Compare that to ~9% of the genome being subject to selection and you get 71% of the genome that is supposedly functional but evolution doesn't care about at all (i.e., it doesn't affect survival and reproduction). If it means nothing to survival or reproduction, what "function" is it serving? Or conversely, if it is functional, why is it immaterial to survival and reproduction if 7/8 of it is rearranged or thrown away? There are more quite good reasons to consider this DNA unimportant - for instance, the genetic load argument. But here's an article by folks who, unlike me, actually appear to know what they're talking about: The Case for Junk DNA Here's a link to a list with percentages. I'd be interested to know what you think. Sandwalk: Theme: Genomes & Junk DNA One never knows, do one? - Fats Waller The fairest thing we can experience is the mysterious. It is the fundamental emotion which stands at the cradle of true art and true science. - Einstein Computer, Audirvana -> optical Ethernet to Fitlet3 -> Fibbr Alpha Optical USB -> iFi NEO iDSD DAC -> Apollon Audio 1ET400A Mini (Purifi based) -> Vandersteen 3A Signature. Link to comment
Jud Posted January 4, 2017 Author Share Posted January 4, 2017 So called "junk" DNA or non coding regions have effects that go beyond the more straightforward specification of the amino acids in a protein. They can be involved in the regulation of gene activity and the structure of the entire chromosome itself. https://www.ncbi.nlm.nih.gov/m/pubmed/20300217/ Yes, that's separate from epigenetics. One never knows, do one? - Fats Waller The fairest thing we can experience is the mysterious. It is the fundamental emotion which stands at the cradle of true art and true science. - Einstein Computer, Audirvana -> optical Ethernet to Fitlet3 -> Fibbr Alpha Optical USB -> iFi NEO iDSD DAC -> Apollon Audio 1ET400A Mini (Purifi based) -> Vandersteen 3A Signature. Link to comment
jabbr Posted January 4, 2017 Share Posted January 4, 2017 Yes, that's separate from epigenetics. Is it? What is your understanding of epigenetics? Custom room treatments for headphone users. Link to comment
Abtr Posted January 4, 2017 Share Posted January 4, 2017 Relatively small populations, yes. "Little evolutionary pressure" is a misunderstanding of the article. I don't think so.. According to the article you referred to: "in small populations, selection is weak and only strongly deleterious mutations are weeded out by purifying selection; and conversely, only strongly advantageous mutations are fixed by positive selection." And the article continues: "the weak evolutionary regime promotes evolution of phenotypic complexity. Precisely because many genomic changes cannot be efficiently eliminated, routes of evolution that are blocked under strong selection open up." Finally the article concludes: "The pervasive exaptation in complex organisms evolving in the weak selection regime appears as a striking paradox: the overall non-adaptive character of evolution in these organisms enables numerous adaptations which ultimately lead to the dramatic rise in organismal complexity. In a higher abstraction plane, though, this is a phenomenon familiar to physicists: entropy increase begets complexity by creating multiple opportunities for the evolution of the system." No. We evolved from common ancestors with animals like bats, dogs, whales, etc., so our hearing has actually become much *less* keen over evolutionary time. You have taken a paper that explicitly cautions against finding "the best of all possible worlds" in our genes and turned it into the exact opposite of what was intended. I don't think I did.. IMO the point of the paper is that we must look at the genetic *mechanisms* that operate under weak selection pressure in relatively small populations in order to understand our own evolution. We simply couldn't have become the complex, highly evolved species that we are without hundreds of millions of years of weak selection and lots of resulting so-called 'junk' DNA/RNA which represents a rich source for 'exaptation'. (Note that also in artificial genetic algorithms, too much 'selection pressure' will generally result in premature convergence of the population on a sub-optimal solution to a problem.) Frankly, I don't quite see how this paper supports your claim that *Chances Are Our Hearing Didn't Evolve "To Do" Anything*, just by explaining how genetic evolution of complex organisms works. Where did the author even vaguely imply that our hearing (or other modalities) didn't evolve to do anything? And with such powerful genetics who is to say that our hearing didn't evolve any further than the hearing of big apes? At least I'm sure that our cognitive processing of what we hear is far superior to apes. Maybe that explains why we love music so much.. Current audio system Link to comment
wgscott Posted January 4, 2017 Share Posted January 4, 2017 for instance ERV (endogenous retrovirus) sequences that are pervasively transcribed (because that's what virus DNA does, even after it's been absorbed into the human genome) was counted as functional. How do you know the RNA transcripts have no function? They could be intermediates in retro-transposition (because that's what retrotransposons do), they could be regulatory RNAs (because that's what interfering RNA genes do), etc. The argument is hardly compelling. Also, transcription is expensive, and a useless RNA transcript is a costly extravagence for a cell, which at leasts suggests that there might be a reason why transcription of these sequences (via RNA interference, because that is what RNAi does) is preserved. The mechanism for generating antibody diversity, for example, is evolutionarily related to retrotransposons and their recombinases. You can't just dismiss this stuff as junk because you haven't identified the function. Link to comment
Jud Posted January 4, 2017 Author Share Posted January 4, 2017 Is it? Yep. Ever read Sean B. Carroll's books The Making of the Fittest and Endless Forms Most Beautiful? They're about heritable changes in regulatory DNA that last for evolutionary time scales, into the hundreds of millions of years. Contrast that with epigenetics (the following is quoted from an Atlantic magazine article by Carl Zimmer about a recent Royal Society meeting of scientists who want to expand current evolutionary theory in various ways): Some studies indicate that—under certain circumstances—an epigenetic change in a parent may get passed down to its offspring. And those children may pass down this altered epigenetic profile to their children. This would be kind of heredity that’s beyond genes. The evidence for this effect is strongest in plants. In one study, researchers were able to trace down altered methylation patterns for 31 generations in a plant called Arabidopsis. And this sort of inheritance can make a meaningful difference in how an organism works. In another study, researchers found that inherited methylation patterns could change the flowering time of Arabidopsis, as well as the size of its roots. The variation that these patterns created was even bigger than what ordinary mutations caused. After presenting evidence like this, Jablonka argued that epigenetic differences could determine which organisms survived long enough to reproduce. “Natural selection could work on this system,” she said. So on one hand you've got regulatory DNA changes that last for hundreds of millions of years. On the other hand you've got someone arguing for an expansion of evolutionary theory by pointing out that some epigenetic changes may last as long as 31 generations, so they could perhaps become candidates for natural selection to act on them. Hundreds of millions of years vs. 31 generations (in an extreme case) is, I would argue, a rather significant difference. One never knows, do one? - Fats Waller The fairest thing we can experience is the mysterious. It is the fundamental emotion which stands at the cradle of true art and true science. - Einstein Computer, Audirvana -> optical Ethernet to Fitlet3 -> Fibbr Alpha Optical USB -> iFi NEO iDSD DAC -> Apollon Audio 1ET400A Mini (Purifi based) -> Vandersteen 3A Signature. Link to comment
Jud Posted January 4, 2017 Author Share Posted January 4, 2017 How do you know the RNA transcripts have no function? They could be intermediates in retro-transposition (because that's what retrotransposons do), they could be regulatory RNAs (because that's what interfering RNA genes do), etc. The argument is hardly compelling. Also, transcription is expensive, and a useless RNA transcript is a costly extravagence for a cell, which at leasts suggests that there might be a reason why transcription of these sequences (via RNA interference, because that is what RNAi does) is preserved. The mechanism for generating antibody diversity, for example, is evolutionarily related to retrotransposons and their recombinases. You can't just dismiss this stuff as junk because you haven't identified the function. That's true (that you can't dismiss it as junk because you haven't identified the function). So what do you think of the arguments in the PLOS Genetics paper (including genetic load) and the list in the Sandwalk post? Well supported enough to pass the "you can't dismiss it just because you haven't identified the function" test? One other question: Why do salamanders have a genome 40 times the size of the human genome? Is it because salamanders have 40 times the genetic functions we do? One never knows, do one? - Fats Waller The fairest thing we can experience is the mysterious. It is the fundamental emotion which stands at the cradle of true art and true science. - Einstein Computer, Audirvana -> optical Ethernet to Fitlet3 -> Fibbr Alpha Optical USB -> iFi NEO iDSD DAC -> Apollon Audio 1ET400A Mini (Purifi based) -> Vandersteen 3A Signature. Link to comment
jabbr Posted January 4, 2017 Share Posted January 4, 2017 Yep. Ever read Sean B. Carroll's books The Making of the Fittest and Endless Forms Most Beautiful? They're about heritable changes in regulatory DNA that last for evolutionary time scales, into the hundreds of millions of years. Contrast that with epigenetics (the following is quoted from an Atlantic magazine article by Carl Zimmer about a recent Royal Society meeting of scientists who want to expand current evolutionary theory in various ways): So on one hand you've got regulatory DNA changes that last for hundreds of millions of years. On the other hand you've got someone arguing for an expansion of evolutionary theory by pointing out that some epigenetic changes may last as long as 31 generations, so they could perhaps become candidates for natural selection to act on them. Hundreds of millions of years vs. 31 generations (in an extreme case) is, I would argue, a rather significant difference. Jud, you would do better by at least making a cursory attempt to read the article I referenced before blindly dismissing its relation to epigenetics. You might learn something. Custom room treatments for headphone users. Link to comment
Jud Posted January 4, 2017 Author Share Posted January 4, 2017 Jud, you would do better by at least making a cursory attempt to read the article I referenced before blindly dismissing its relation to epigenetics. You might learn something. I'm happy to do that, and I wasn't dismissing the article. What the article is talking about are changes that have propagated for tens of millions of years. What the popular press and the Royal Society conference I mentioned were referring to as "epigenetics" is the neo-Lamarckian issue: whether environmental non-genetic changes induced in a life form (such as the studies where ancestral diets affect metabolism and lifespan of offspring, Your Diet Affects Your Grandchildren's DNA, Scientists Say) can impact the evolution of a population. It is these sorts of changes that are limited to a few tens of generations at most, and thus effects on evolution are very, very speculative at best. One never knows, do one? - Fats Waller The fairest thing we can experience is the mysterious. It is the fundamental emotion which stands at the cradle of true art and true science. - Einstein Computer, Audirvana -> optical Ethernet to Fitlet3 -> Fibbr Alpha Optical USB -> iFi NEO iDSD DAC -> Apollon Audio 1ET400A Mini (Purifi based) -> Vandersteen 3A Signature. Link to comment
Jud Posted January 4, 2017 Author Share Posted January 4, 2017 That's true (that you can't dismiss it as junk because you haven't identified the function). So what do you think of the arguments in the PLOS Genetics paper (including genetic load) and the list in the Sandwalk post? Well supported enough to pass the "you can't dismiss it just because you haven't identified the function" test? One other question: Why do salamanders have a genome 40 times the size of the human genome? Is it because salamanders have 40 times the genetic functions we do? Sorry, one additional question: What evidence of what you would consider to be "function" does lack of selection constitute? In other words, if a DNA sequence is mutating at the background rate, do you consider that evidence of non-function ("junk"), and if you do, would you say it is strong evidence? One never knows, do one? - Fats Waller The fairest thing we can experience is the mysterious. It is the fundamental emotion which stands at the cradle of true art and true science. - Einstein Computer, Audirvana -> optical Ethernet to Fitlet3 -> Fibbr Alpha Optical USB -> iFi NEO iDSD DAC -> Apollon Audio 1ET400A Mini (Purifi based) -> Vandersteen 3A Signature. Link to comment
wgscott Posted January 4, 2017 Share Posted January 4, 2017 Depends upon what the gene product is. If it is a protein, for example, it may be able to tolerate a fairly high mutation rate, but if it is a structured RNA, or a regulatory RNA, perhaps much less so. Link to comment
jabbr Posted January 4, 2017 Share Posted January 4, 2017 Sorry, one additional question: What evidence of what you would consider to be "function" does lack of selection constitute? In other words, if a DNA sequence is mutating at the background rate, do you consider that evidence of non-function ("junk"), and if you do, would you say it is strong evidence? Certainly not evidence of non-function. How would you consider regions that mutate at an accelerated rate? Custom room treatments for headphone users. Link to comment
Jud Posted January 4, 2017 Author Share Posted January 4, 2017 Depends upon what the gene product is. If it is a protein, for example, it may be able to tolerate a fairly high mutation rate, but if it is a structured RNA, or a regulatory RNA, perhaps much less so. Do you believe this could result in no evidence of selection on a DNA sequence whose product may nonetheless be vital to survival and reproduction, in numbers sufficient to make up the difference between ENCODE's 80% and the ~9% of the genome that shows evidence of selection? Sent from my iPhone using Computer Audiophile One never knows, do one? - Fats Waller The fairest thing we can experience is the mysterious. It is the fundamental emotion which stands at the cradle of true art and true science. - Einstein Computer, Audirvana -> optical Ethernet to Fitlet3 -> Fibbr Alpha Optical USB -> iFi NEO iDSD DAC -> Apollon Audio 1ET400A Mini (Purifi based) -> Vandersteen 3A Signature. Link to comment
wgscott Posted January 4, 2017 Share Posted January 4, 2017 If you had a 10,000 nucleotide pri-miRNA transcript that was processed by drosha and dicer to excise a semi-conserved 21-base-pair helical element, your statistical analysis would tell you that it was unconserved junk. Hence that kind of approach is inherently flawed. Link to comment
jabbr Posted January 4, 2017 Share Posted January 4, 2017 I'm happy to do that, and I wasn't dismissing the article. What the article is talking about are changes that have propagated for tens of millions of years. The article I referenced regards the architecture of the nucleus itself and so involves structural mechanism by which regions of chromosomes are turned on and off -- thus goes way beyond issues which only involve inheritance. When a complex organism forms, the preprogrammed and hence inherited are involved in a highly complex series of steps in which chromosome regions are organized, turned on and off, differentiated etc. This involves epigenetic mechanisms e.g. methylation and histone binding. Moreover it has been long known that certain regions are preserved but others have increased mutation rates and consider that there are heritable mechanisms for that as well -- indeed these regions including SNPs are not random and are involved in their own biologically active mechanisms. Custom room treatments for headphone users. Link to comment
jabbr Posted January 4, 2017 Share Posted January 4, 2017 Do you believe this could result in no evidence of selection on a DNA sequence whose product may nonetheless be vital to survival and reproduction, in numbers sufficient to make up the difference between ENCODE's 80% and the ~9% of the genome that shows evidence of selection? Not entirely sure what you mean but, for example, while the ability to form antibodies is inherited, highly polymorphic regions allow specific antibodies to be generated. Since the antibodies are not produced by the eggs nor spermatogenic cells, such polymorphisms are not inherited -- get the point? Custom room treatments for headphone users. Link to comment
wgscott Posted January 4, 2017 Share Posted January 4, 2017 Another way to look at it, why would a promotor sequence (the binding site sequence for the RNA polymerase, that makes transcription possible) be preserved if the transcript served no function and in fact was energetically costly to produce? Link to comment
Ralf11 Posted January 4, 2017 Share Posted January 4, 2017 as an aside, it is always interesting to me when people try to discuss something in a technical area that is outside their training... you 2 or 3 other other guys know who you aren't Link to comment
Jud Posted January 4, 2017 Author Share Posted January 4, 2017 Another way to look at it, why would a promotor sequence (the binding site sequence for the RNA polymerase, that makes transcription possible) be preserved if the transcript served no function and in fact was energetically costly to produce? Was it "preserved" or just not cleared at the background rate of mutation? It's one of the central points of the article I linked in the original post that this clearance doesn't happen efficiently at the relatively smaller effective population sizes of non-microscopic life, whereas in bacteria the very same energetic cost is acted on efficiently by selection and results in very little "junk." Sent from my iPhone using Computer Audiophile One never knows, do one? - Fats Waller The fairest thing we can experience is the mysterious. It is the fundamental emotion which stands at the cradle of true art and true science. - Einstein Computer, Audirvana -> optical Ethernet to Fitlet3 -> Fibbr Alpha Optical USB -> iFi NEO iDSD DAC -> Apollon Audio 1ET400A Mini (Purifi based) -> Vandersteen 3A Signature. Link to comment
Jud Posted January 4, 2017 Author Share Posted January 4, 2017 The article I referenced regards the architecture of the nucleus itself and so involves structural mechanism by which regions of chromosomes are turned on and off -- thus goes way beyond issues which only involve inheritance. When a complex organism forms, the preprogrammed and hence inherited are involved in a highly complex series of steps in which chromosome regions are organized, turned on and off, differentiated etc. This involves epigenetic mechanisms e.g. methylation and histone binding. Moreover it has been long known that certain regions are preserved but others have increased mutation rates and consider that there are heritable mechanisms for that as well -- indeed these regions including SNPs are not random and are involved in their own biologically active mechanisms. Of course. We have no argument about any of this. It is almost certainly my use of "epigenetics" in the neo-Lamarckian way it's been talked about in the popular science press and by some scientists lately that has caused the apparent confusion, for which I apologize. I (and they) are talking purely about the role of epigenetics in the supposed inheritance of acquired characteristics - giraffes stretching their necks as they reach for leaves and passing the longer necks thus acquired on to their descendants, that sort of thing. Sent from my iPhone using Computer Audiophile One never knows, do one? - Fats Waller The fairest thing we can experience is the mysterious. It is the fundamental emotion which stands at the cradle of true art and true science. - Einstein Computer, Audirvana -> optical Ethernet to Fitlet3 -> Fibbr Alpha Optical USB -> iFi NEO iDSD DAC -> Apollon Audio 1ET400A Mini (Purifi based) -> Vandersteen 3A Signature. Link to comment
wgscott Posted January 4, 2017 Share Posted January 4, 2017 Was it "preserved" or just not cleared at the background rate of mutation? I would argue the two are the same. Link to comment
jabbr Posted January 5, 2017 Share Posted January 5, 2017 Of course. We have no argument about any of this. It is almost certainly my use of "epigenetics" in the neo-Lamarckian way it's been talked about in the popular science press and by some scientists lately that has caused the apparent confusion, for which I apologize. I (and they) are talking purely about the role of epigenetics in the supposed inheritance of acquired characteristics - giraffes stretching their necks as they reach for leaves and passing the longer necks thus acquired on to their descendants, that sort of thing. Oh gosh ... I had to look that up because, frankly, don't think in these terms. First of all, most of these truly epigenetic changes are clearly, probably unquestionably, tissue specific -- this has been known for many decades. So consider something like this: suppose you've become a violin concertmaster through decades of hard work and practice for hours per day. Could that be passed on to your offspring? Now I'm NOT talking about a skin flute player on purpose here. Get the joke? Point being that any neuromuscular expertise that is purely acquired doesn't reside in the gonads and so can't be inherited in that fashion! Secondly, the interest in epigenetics, is, at least on my part, more regarding how tissues may develop certain "memories", express certain proteins or develop certain characteristics e.g. why does the liver produce bile while the adrenals produce cortisol etc. i.e. how does developmental biological processes actually occur on a molecular level. I think there is probably a big misnomer among the general population that "genetics" primarily is the study of inheritance, whereas among scientists it is more about the study of molecular biology and how things work. And BTW giraffe's necks would be most likely classical Darwinian evolution. No expectation that giraffe's who were raised to bend down for their food would lose their necks Custom room treatments for headphone users. Link to comment
Jud Posted January 5, 2017 Author Share Posted January 5, 2017 I would argue the two are the same. Are you saying there is no such thing as an effect of selection on the genome (e.g., more rapid fixation of advantageous mutations than the background rate, conservation of essential sequences for longer than would be the case if these sequences mutated at the background rate), that it happens but cannot be reliably detected, or something else? One never knows, do one? - Fats Waller The fairest thing we can experience is the mysterious. It is the fundamental emotion which stands at the cradle of true art and true science. - Einstein Computer, Audirvana -> optical Ethernet to Fitlet3 -> Fibbr Alpha Optical USB -> iFi NEO iDSD DAC -> Apollon Audio 1ET400A Mini (Purifi based) -> Vandersteen 3A Signature. Link to comment
Jud Posted January 5, 2017 Author Share Posted January 5, 2017 And BTW giraffe's necks would be most likely classical Darwinian evolution. No expectation that giraffe's who were raised to bend down for their food would lose their necks Giraffe's necks being a result of natural selection, sure. The discredited (but now making a bit of a comeback couched in "epigenetics" in certain circles, as I alluded to) Lamarckian explanation would be analogous to your concertmaster example - that by reaching for food individuals lengthened their necks, and passed this trait acquired during life to their offspring. One never knows, do one? - Fats Waller The fairest thing we can experience is the mysterious. It is the fundamental emotion which stands at the cradle of true art and true science. - Einstein Computer, Audirvana -> optical Ethernet to Fitlet3 -> Fibbr Alpha Optical USB -> iFi NEO iDSD DAC -> Apollon Audio 1ET400A Mini (Purifi based) -> Vandersteen 3A Signature. Link to comment
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