Epigenetics: The Evolution Revolution
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I think people tend to conflate these two ideas.
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.
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).
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.
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...
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.
Epigenetics is not "how the genome is read" in any meaningful way. Epigenetics is more like encoding tone of voice transcription factors ought to use when they read the genome. Should they whisper or shout? Epigenetics does not do the actual reading of the genome, or change the underlying data in the base sequence. There are not "various readings" of the genome, no matter what you think.
So you haven't read the paper then. Perhaps you also don't understand the difference between mediates and regulates. KDM6B does not regulate the response to temperature. Temperature regulates something (unknown) that regulates KDM6B, which epigenetically regulates something else (in this case, DMRT1, a transcription factor) which regulates a bunch of other things (mostly unknown) that cause the gonadal soma to become testes or ovaries.
That epigenetics should play a bit part in some developmental process like this is essentially a trivial observation, and treating it as significant betrays a lack of understanding. All the genes in all the cells are wrapped around histones which are modified to make the underlying genes more or less active, all the time. So epigenetics a part of gene regulation, but it's hardly the most powerful or important one. It's like waxing poetic over the importance of uridine metabolism, because without uridine there is no RNA. It's true, but in a totally boring way.
As far as transgenerational epigenetics goes, essentially all of the literature in mammals is missing the key controls to rule out regular genetics. You should regard everything you read about it with extreme skepticism. It's a hot field with a lot of hype and pretty lax standards.
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.
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.
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.
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/61/8/588/336...
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_experime...
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.
Even if the straw-man "everybody is totally equal" can't stand up, I think there's a good argument for:
"We have to assume everybody is equal by default,(A) because we are absolutely too ignorant and limited to determine the long-term value or trade-offs within a gene or gene-combination, (B) because some diversity is itself a collective benefit to the species, and (C) because history shows most people who claimed they had the answers were often wrong and racist."
Does anyone know of anyone who became a racist because they looked at the scientific literature? My experience is people become racist for a variety of reasons and then (occasionally) draw upon a paraody of science to try and justify their beliefs.
Maybe here in the West, but something tells me China isn't going to get caught up in either the ethical or political implications of such research. They'll just do it and quickly operationalize (or weaponize) whatever they discover as fast as possible.
Everyone familiar with history knows the consequences of surveillance, most people don't like surveillance but is that stopping anyone?
China is not the one bombing random countries and killing hundreds of thousands of people and setting entire societies back decades. These are crimes against humanity with no accountability and consequences for those involved so where is the ethics and morality? China is not the one who used just discovered nuclear weapons recklessly on a civilian population, not once but twice.
Blanket statement of ethics and morality are meaningless when not consistent with actions on the ground. They merely serve to fabricate a non existent moral high ground whose existence requires a denial and diminishment of one own actions while pointing fingers and demonizing others. Posturing may be fun but ignoring the ethical deterioration in your own society has consequences.
"We also have extreme difficulty parsing what may be caused by (epi)genetics and what may be caused by differences in experiences or development"
Not only do we lack fine-grained data with which to make that comparison, we probably lack the epistemological capabilities and experimental infrastructure to even attempt gathering such data.
This doesn't have to be mutually exclusive with the argument(s) that population-scale difference in distribution of [whatever] have been experimentally observed. It's just that for most conceivable [whatever] with some kind of relevant social impact, we still can't assign causality with high confidence to the actual (epi)genetics themselves.
Can you give an example?
Also, cuddle your kids: http://www.sciencealert.com/cuddling-babies-alters-their-gen...