6 ms·

Epigenetics: The Evolution Revolution

115 points by techrede 8y ago

mxwsn 8y ago
The impact of epigenetics can be powerful. A neat example is sex, one of the most obvious and striking axes of biological variation. Unlike humans where the presence or absence of an entire chromosome (X or Y) determines sex, there are turtles and reptiles that determine their sex based on ambient temperature alone. The logical consequence is that a pair of female and male turtle twins can share exactly the same genome yet be different sexes — their sex is determined solely by how their genome is read (epigenetics).
- learned 8y ago
  There is also some really interesting epigenetics research focusing on age-related disease. For example, Steve Horvath's group at UCLA has been refining an "epigenetic clock" using DNA methylation data to predict all-cause mortality in several species with a relatively simple test. It has the potential to be an incredibly valuable metric in the field going forward.
- azeotropic 8y ago
  Epigenetics is not "how the genome is read" -- you're describing the normal action of transcription factors. Epigenetics is heritable information that is not encoded in DNA base sequence. Common mechanisms include DNA methylation patterns, histone binding patterns, and histone modifications, all of which can be stably inherited from one cell division to the next, but not necessarily transgenerationally, from parent to offspring, through the germ line. You are also confused about turtle sex determination. The master regulator of sex determination (which must respond directly to temperature) is unknown. The epigenetic regulator KDM6B is required to mediate the temperature signal for male development, but there is no evidence that it is the master regulator. Maybe you read a press release instead of the actual paper in Science. Environmental sex determination is not that unusual, and need not depend on epigenetics or even transcription factors.
  - mxwsn 8y ago
    "Epigenetics is heritable information that is not encoded in DNA base sequence." I agree with this. Combined with the observation that temperature-dependent sex determination occurs within a specific window of time, after which sex cannot be changed for the remainder of the organism's lifetime, I believe it follows logically that somatic cells (certainly those within the sexual organs) must be receiving heritable information not encoded in DNA base sequence from their adult stem cells. Thus environmental sex determination must occur through epigenetics as you have defined. To the best of my knowledge, DNA methylation patterns, histone binding patterns, and histone modifications all have causal biological impacts solely by their causal influence on "how the genome is read". Epigenetics is "how the genome is read", as well as more beyond that. But how the genome is read is substantial portion of epigenetics and, for better or worse, the aspect of epigenetics that receives the most attention when discussed with general audiences. I think it's inaccurate to deny the role of "various readings" of the genome in a definition of epigenetics. I'm unsure how your citing of KDM6B is related to or addresses any confusion in my statement on temperature-dependent sex determination. From what I can understand, you point out that KDM6B histone demethylase acts epigenetically and that it regulates temperature-dependent sex-determination, both of which are consistent with what I said earlier...
    - toasterlovin 8y ago
      > Epigenetics is "how the genome is read" I'm not a molecular biologist, so take this all with a grain of salt. There are two things which get confused when discussing epigenetics. First, you have gene expression which is mediated by the environment. That is what you are talking about with your turtle example. This is pretty common. After all, being able to respond to environmental stimuli is useful. But there is another phenomena that gets labelled as epigenetics: stuff in the environment which modifies the DNA of the germ line cells (eggs and sperm) of an organism. The part about it being germ line cells is important, because that means that the changes to DNA will be passed on to the offspring, whereas epigenetic changes in any of the other cells of the body will not. People are in love with this aspect of epigenetics because, frankly, there's a certain type of person who is enamored with the idea that this might "disprove" Darwinian evolution (OMG Lamarck was right!). It's extremely frustrating because this second phenomena is, as far as we know, extremely uncommon. I mean, it almost has to be. Large organisms are like a house of cards; if you make too many changes, everything comes crashing down. So, if there were epigenetic changes to germ line DNA happening all the time, there would be unfeasible levels of mutation happening from one generation to the next. But the fact that it is extremely uncommon does not stop people from hearing about how this second meaning of epigenetics is a weird end-run around Darwinian evolution, then hearing about how common the first meaning of epigenetics is, and coming to the conclusion that Darwinian evolution is invalid. Incidentally, these two meanings are the root cause of you and the person who responded to you misunderstanding each other.
daemonk 8y ago
There should be a better distinction made between EPIgenetics and epiGENETICS. The former is more about regulatory mechanisms (methylation, histone modifications, polycomb-like mechanisms, etc) on top of our DNA. The latter is more about non-DNA inheritance of information across generation, which is not completely clear yet. I think people tend to conflate these two ideas.
- asdff 8y ago
  I think most people don't even know that much, this isn't something that is deeply covered in most intro to bio courses in college; you have to learn a bit about how DNA is packaged and transcribed which you'd get in upper division courses. At least in the field, there is no confusion. Non-DNA inheritance is inheritance of these epigenetic regulatory states in which you've described, but the term used specifically for this is transgenerational inheritance.
- Nomentatus 8y ago
  We shouldn't assume we know all mechanisms, true. I do believe I've read of RNA changes retained over generations but could be wrong about that.
ancorevard 8y ago
Looks like the theory of evolution needs modifications due to epigenetics.
- teilo 8y ago
  Not sure why this is being downvoted, but it's definitely the case that as we learn more about epigenetics, we will need to modify our understanding of evolution substantially, particularly the relationship between epigenetic expression and mutation, in which the latter can "lock in" the changes from the former and lead to more rapid speciation. Exciting stuff.
  - asdff 8y ago
    I think the existing understanding of evolution is still fine. Darwin wrote, 1.More individuals are produced each generation that can survive. 2. Phenotypic variation exists among individuals and the variation is heritable. 3. Those individuals with heritable traits better suited to the environment will survive. 4. When reproductive isolation occurs new species will form. When Darwin proposed this, he didn't have any idea of molecular genetics, let alone epigenetics. Mendel too wrote about alleles but he didn't know about base pairs of DNA. Evolution really only concerns phenotypic variation, not the underlying basis for it, so it doesn't matter if the variation is due to a genetic or epigenetic change.
    - deleted 8y ago
      [deleted]
  - toasterlovin 8y ago
    People like to get carried away with epigenetics. It's not a revolution in our understanding of evolution. At least not at this point. The Darwinian model still explains basically everything you need to know about evolution. Epigenetics (by which I mean environmental changes to germ line DNA) is what software engineers would call an edge case.
- danieltillett 8y ago
  No. Natural selection happens at the level of the phenotype not the genotype. Anyway a gene is not a piece of DNA, but a unit of heredity. The reason why epigentics is less important in evolution is because it is unstable. If an environmental factor can shift the phenotype one way then another factor can shift it back. Most of these unstable epigenetic changes wash out in an evolutionary short time frame.
whataretensors 8y ago
Slippery slope here. Most people don't understand or accept evolution, even engineers. For example, anyone who accepts equitable distribution of attributes across genetic variances(a commonly accepted social narrative). Evolution is messy. Epigenetics makes it even messier. We have to be careful not to conflate the value of someone by anything genetic. Especially not epigenetics, which seems from this article to be related to childhood trauma. I'm interested in how we can use AI to modify genetic code to improve and fix our past epigenetic and genetic shortcomings.
- killjoywashere 8y ago
  I gather you watched Google's Selfish Ledger video?
- mrkurt 8y ago
  > For example, anyone who accepts equitable distribution of attributes across genetic variances(a commonly accepted social narrative). Can you give an example?
  - GauntletWizard 8y ago
    Don't feel the trolls. It's a racist dogwhistle.
    - elefanten 8y ago
      You read that comment with bad understanding or bad faith. They explicitly argue against tying (epi)genetics to evaluating someone's potential. Whether you agree with that guidance or not, whether you agree with the implications, such data exists. Trying to wish it away contributes to the toxic hellstorm that exists in public discourse around these subjects. It retrenches the people who are curious about it and sends them into the narrative arms of the people who want to misuse it for their own social ends. It's much more productive to argue why such data is extremely limited, poorly understood and not conclusive.
    - whataretensors 8y ago
deleted 8y ago
[deleted]
Nomentatus 8y ago
"What findings have made it possible?" Recent evidence is cited, but it's interesting to note that evidence of epigenetic effects (that were ignored as known anomalies) is ancient (of course the mechanism wasn't known.) Such as, the Hinny. "Horses and donkeys are both equids, but their evolution diverged millions of years ago. Still, they are closely enough related that they can interbreed. But the hybrids they produce look different from each other depending on whether the mother is a horse or a donkey. If she is a horse, her baby is a mule and has very long ears. If she is a donkey, her baby is a hinny. Hinnies are rare, but they are generally smaller than mules, with shorter ears. People have known for thousands of years that horse—donkey hybrids differ depending on which species is the mother and which the father. The process thought to be responsible for these differences—genomic imprinting—has been known for only a few decades. Genomic imprinting is an epigenetic mechanism, one of the forms of biological inheritance that operate outside the traditional Mendelian mode. Imprinting is a particularly useful model for investigating epigenetic gene regulation and is a major source of epigenetic regulation in the brain. With genomic imprinting, DNA methylation silences some genes or gene clusters—in egg, sperm, or zygote—depending on which parent they came from. For an imprinted gene, the allele from one parent or the other is shut down and makes no product. The other allele is expressed and produces characteristic outcomes in the offspring. Thus, mom's and dad's chromosomes are not functionally the same. Imprinting is required for normal development, although if the functioning imprinted gene is defective, as sometimes happens, the outcome can also be fatal, or at least debilitating. Some 30 serious disorders are attributed to disrupted imprinting. Some are rare, but more common afflictions, such as cancers and autism, have also been linked to genomic imprinting." https://www.academic.oup.com/bioscience/article/61/8/588/336969 https://www.academic.oup.com/bioscience/article/61/8/588/336... Had we cared to investigate this sort of anomaly more closely, I can't help but think that we would have discovered epigenetics decades earlier. I well remember when any such discussion was entirely inadmissable amongst biologists, and proof of one's idiocy if you raised the idea of the genetic mechanism allowing any moderation of DNA as a result of environment or experience (a possibility I did in fact raise in a letter to Jacques Monod in the seventies - only silence came back, such craziness was not worthy of a response.) There's an interesting list of early experiments, some of which may actually have been valid, but were dismissed, here: https://en.wikipedia.org/wiki/Lamarckism#Weismann's_experiment https://en.wikipedia.org/wiki/Lamarckism#Weismann's_experime...
Nomentatus 8y ago
Now that we know all this, do people (capable of having children) have a right to smoke? Do you have a right to significantly harm the health of not just your children, but even your great-grandchildren? Also, cuddle your kids: http://www.sciencealert.com/cuddling-babies-alters-their-genetics-dna-for-years http://www.sciencealert.com/cuddling-babies-alters-their-gen...
dandare 8y ago
In this article there is annoyingly little information about actually permanently passing epigenetic changes to offspring. If that indeed doesn't happen then epigenetics has little to add to evolution.
mannykannot 8y ago
"It is as though nature employs epigenesis to make long-lasting adjustments to an individual’s genetic program to suit his or her personal circumstances, much as in Lamarck’s notion of 'striving for perfection.'" It would be something of a category error to see a rehabilitation of Lamarckism in these discoveries. They show that our previous understanding of information flow across generations was incomplete, but it does not challenge the understanding that evolution occurs through variation and selection. One fundamental problem for Lamarckism is 'how does the body know what is good for it?' Lamarck used as an example the idea that blacksmiths' sons had stronger arms on account of their fathers' work (I do not know whether he considered their daughters...) Putting aside the question of whether that is actually true, suppose that blacksmiths were also prone to musculoskeletal occupational injury. How is the body to 'know' that the stronger arms are desirable but the injury is not, especially if the former is promoted by the micro-injury of constant hammering? The rest of the article contains within itself a long list of deleterious consequences of epigenetic inheritance. While the epigenetic mechanisms probably constrain (or perhaps expand the possibilities for) variation, it does not present a fundamental challenge to Darwinian evolution.

115 points by techrede 8y ago

The impact of epigenetics can be powerful. A neat example is sex, one of the most obvious and striking axes of biological variation. Unlike humans where the presence or absence of an entire chromosome (X or Y) determines sex, there are turtles and reptiles that determine their sex based on ambient temperature alone. The logical consequence is that a pair of female and male turtle twins can share exactly the same genome yet be different sexes — their sex is determined solely by how their genome is read (epigenetics).

learned 8y ago
There is also some really interesting epigenetics research focusing on age-related disease. For example, Steve Horvath's group at UCLA has been refining an "epigenetic clock" using DNA methylation data to predict all-cause mortality in several species with a relatively simple test. It has the potential to be an incredibly valuable metric in the field going forward.
azeotropic 8y ago
Epigenetics is not "how the genome is read" -- you're describing the normal action of transcription factors. Epigenetics is heritable information that is not encoded in DNA base sequence. Common mechanisms include DNA methylation patterns, histone binding patterns, and histone modifications, all of which can be stably inherited from one cell division to the next, but not necessarily transgenerationally, from parent to offspring, through the germ line. You are also confused about turtle sex determination. The master regulator of sex determination (which must respond directly to temperature) is unknown. The epigenetic regulator KDM6B is required to mediate the temperature signal for male development, but there is no evidence that it is the master regulator. Maybe you read a press release instead of the actual paper in Science. Environmental sex determination is not that unusual, and need not depend on epigenetics or even transcription factors.
- mxwsn 8y ago
  "Epigenetics is heritable information that is not encoded in DNA base sequence." I agree with this. Combined with the observation that temperature-dependent sex determination occurs within a specific window of time, after which sex cannot be changed for the remainder of the organism's lifetime, I believe it follows logically that somatic cells (certainly those within the sexual organs) must be receiving heritable information not encoded in DNA base sequence from their adult stem cells. Thus environmental sex determination must occur through epigenetics as you have defined. To the best of my knowledge, DNA methylation patterns, histone binding patterns, and histone modifications all have causal biological impacts solely by their causal influence on "how the genome is read". Epigenetics is "how the genome is read", as well as more beyond that. But how the genome is read is substantial portion of epigenetics and, for better or worse, the aspect of epigenetics that receives the most attention when discussed with general audiences. I think it's inaccurate to deny the role of "various readings" of the genome in a definition of epigenetics. I'm unsure how your citing of KDM6B is related to or addresses any confusion in my statement on temperature-dependent sex determination. From what I can understand, you point out that KDM6B histone demethylase acts epigenetically and that it regulates temperature-dependent sex-determination, both of which are consistent with what I said earlier...
  - toasterlovin 8y ago
    > Epigenetics is "how the genome is read" I'm not a molecular biologist, so take this all with a grain of salt. There are two things which get confused when discussing epigenetics. First, you have gene expression which is mediated by the environment. That is what you are talking about with your turtle example. This is pretty common. After all, being able to respond to environmental stimuli is useful. But there is another phenomena that gets labelled as epigenetics: stuff in the environment which modifies the DNA of the germ line cells (eggs and sperm) of an organism. The part about it being germ line cells is important, because that means that the changes to DNA will be passed on to the offspring, whereas epigenetic changes in any of the other cells of the body will not. People are in love with this aspect of epigenetics because, frankly, there's a certain type of person who is enamored with the idea that this might "disprove" Darwinian evolution (OMG Lamarck was right!). It's extremely frustrating because this second phenomena is, as far as we know, extremely uncommon. I mean, it almost has to be. Large organisms are like a house of cards; if you make too many changes, everything comes crashing down. So, if there were epigenetic changes to germ line DNA happening all the time, there would be unfeasible levels of mutation happening from one generation to the next. But the fact that it is extremely uncommon does not stop people from hearing about how this second meaning of epigenetics is a weird end-run around Darwinian evolution, then hearing about how common the first meaning of epigenetics is, and coming to the conclusion that Darwinian evolution is invalid. Incidentally, these two meanings are the root cause of you and the person who responded to you misunderstanding each other.

daemonk 8y ago

There should be a better distinction made between EPIgenetics and epiGENETICS. The former is more about regulatory mechanisms (methylation, histone modifications, polycomb-like mechanisms, etc) on top of our DNA. The latter is more about non-DNA inheritance of information across generation, which is not completely clear yet. I think people tend to conflate these two ideas.

asdff 8y ago
I think most people don't even know that much, this isn't something that is deeply covered in most intro to bio courses in college; you have to learn a bit about how DNA is packaged and transcribed which you'd get in upper division courses. At least in the field, there is no confusion. Non-DNA inheritance is inheritance of these epigenetic regulatory states in which you've described, but the term used specifically for this is transgenerational inheritance.
Nomentatus 8y ago
We shouldn't assume we know all mechanisms, true. I do believe I've read of RNA changes retained over generations but could be wrong about that.

ancorevard 8y ago

Looks like the theory of evolution needs modifications due to epigenetics.

teilo 8y ago
Not sure why this is being downvoted, but it's definitely the case that as we learn more about epigenetics, we will need to modify our understanding of evolution substantially, particularly the relationship between epigenetic expression and mutation, in which the latter can "lock in" the changes from the former and lead to more rapid speciation. Exciting stuff.
- asdff 8y ago
  I think the existing understanding of evolution is still fine. Darwin wrote, 1.More individuals are produced each generation that can survive. 2. Phenotypic variation exists among individuals and the variation is heritable. 3. Those individuals with heritable traits better suited to the environment will survive. 4. When reproductive isolation occurs new species will form. When Darwin proposed this, he didn't have any idea of molecular genetics, let alone epigenetics. Mendel too wrote about alleles but he didn't know about base pairs of DNA. Evolution really only concerns phenotypic variation, not the underlying basis for it, so it doesn't matter if the variation is due to a genetic or epigenetic change.
  - deleted 8y ago
    [deleted]
- toasterlovin 8y ago
  People like to get carried away with epigenetics. It's not a revolution in our understanding of evolution. At least not at this point. The Darwinian model still explains basically everything you need to know about evolution. Epigenetics (by which I mean environmental changes to germ line DNA) is what software engineers would call an edge case.
danieltillett 8y ago
No. Natural selection happens at the level of the phenotype not the genotype. Anyway a gene is not a piece of DNA, but a unit of heredity. The reason why epigentics is less important in evolution is because it is unstable. If an environmental factor can shift the phenotype one way then another factor can shift it back. Most of these unstable epigenetic changes wash out in an evolutionary short time frame.

whataretensors 8y ago

Slippery slope here. Most people don't understand or accept evolution, even engineers. For example, anyone who accepts equitable distribution of attributes across genetic variances(a commonly accepted social narrative). Evolution is messy. Epigenetics makes it even messier. We have to be careful not to conflate the value of someone by anything genetic. Especially not epigenetics, which seems from this article to be related to childhood trauma. I'm interested in how we can use AI to modify genetic code to improve and fix our past epigenetic and genetic shortcomings.

killjoywashere 8y ago
I gather you watched Google's Selfish Ledger video?
mrkurt 8y ago
> For example, anyone who accepts equitable distribution of attributes across genetic variances(a commonly accepted social narrative). Can you give an example?
- GauntletWizard 8y ago
  Don't feel the trolls. It's a racist dogwhistle.
  - elefanten 8y ago
    You read that comment with bad understanding or bad faith. They explicitly argue against tying (epi)genetics to evaluating someone's potential. Whether you agree with that guidance or not, whether you agree with the implications, such data exists. Trying to wish it away contributes to the toxic hellstorm that exists in public discourse around these subjects. It retrenches the people who are curious about it and sends them into the narrative arms of the people who want to misuse it for their own social ends. It's much more productive to argue why such data is extremely limited, poorly understood and not conclusive.
  - whataretensors 8y ago

deleted 8y ago

[deleted]

Nomentatus 8y ago

"What findings have made it possible?" Recent evidence is cited, but it's interesting to note that evidence of epigenetic effects (that were ignored as known anomalies) is ancient (of course the mechanism wasn't known.) Such as, the Hinny. "Horses and donkeys are both equids, but their evolution diverged millions of years ago. Still, they are closely enough related that they can interbreed. But the hybrids they produce look different from each other depending on whether the mother is a horse or a donkey. If she is a horse, her baby is a mule and has very long ears. If she is a donkey, her baby is a hinny. Hinnies are rare, but they are generally smaller than mules, with shorter ears. People have known for thousands of years that horse—donkey hybrids differ depending on which species is the mother and which the father. The process thought to be responsible for these differences—genomic imprinting—has been known for only a few decades. Genomic imprinting is an epigenetic mechanism, one of the forms of biological inheritance that operate outside the traditional Mendelian mode. Imprinting is a particularly useful model for investigating epigenetic gene regulation and is a major source of epigenetic regulation in the brain. With genomic imprinting, DNA methylation silences some genes or gene clusters—in egg, sperm, or zygote—depending on which parent they came from. For an imprinted gene, the allele from one parent or the other is shut down and makes no product. The other allele is expressed and produces characteristic outcomes in the offspring. Thus, mom's and dad's chromosomes are not functionally the same. Imprinting is required for normal development, although if the functioning imprinted gene is defective, as sometimes happens, the outcome can also be fatal, or at least debilitating. Some 30 serious disorders are attributed to disrupted imprinting. Some are rare, but more common afflictions, such as cancers and autism, have also been linked to genomic imprinting." https://www.academic.oup.com/bioscience/article/61/8/588/336969 https://www.academic.oup.com/bioscience/article/61/8/588/336... Had we cared to investigate this sort of anomaly more closely, I can't help but think that we would have discovered epigenetics decades earlier. I well remember when any such discussion was entirely inadmissable amongst biologists, and proof of one's idiocy if you raised the idea of the genetic mechanism allowing any moderation of DNA as a result of environment or experience (a possibility I did in fact raise in a letter to Jacques Monod in the seventies - only silence came back, such craziness was not worthy of a response.) There's an interesting list of early experiments, some of which may actually have been valid, but were dismissed, here: https://en.wikipedia.org/wiki/Lamarckism#Weismann's_experiment https://en.wikipedia.org/wiki/Lamarckism#Weismann's_experime...

Nomentatus 8y ago

Now that we know all this, do people (capable of having children) have a right to smoke? Do you have a right to significantly harm the health of not just your children, but even your great-grandchildren? Also, cuddle your kids: http://www.sciencealert.com/cuddling-babies-alters-their-genetics-dna-for-years http://www.sciencealert.com/cuddling-babies-alters-their-gen...

dandare 8y ago

In this article there is annoyingly little information about actually permanently passing epigenetic changes to offspring. If that indeed doesn't happen then epigenetics has little to add to evolution.

mannykannot 8y ago

"It is as though nature employs epigenesis to make long-lasting adjustments to an individual’s genetic program to suit his or her personal circumstances, much as in Lamarck’s notion of 'striving for perfection.'" It would be something of a category error to see a rehabilitation of Lamarckism in these discoveries. They show that our previous understanding of information flow across generations was incomplete, but it does not challenge the understanding that evolution occurs through variation and selection. One fundamental problem for Lamarckism is 'how does the body know what is good for it?' Lamarck used as an example the idea that blacksmiths' sons had stronger arms on account of their fathers' work (I do not know whether he considered their daughters...) Putting aside the question of whether that is actually true, suppose that blacksmiths were also prone to musculoskeletal occupational injury. How is the body to 'know' that the stronger arms are desirable but the injury is not, especially if the former is promoted by the micro-injury of constant hammering? The rest of the article contains within itself a long list of deleterious consequences of epigenetic inheritance. While the epigenetic mechanisms probably constrain (or perhaps expand the possibilities for) variation, it does not present a fundamental challenge to Darwinian evolution.