15 Comments
Dec 19, 2022Liked by Razib Khan

Thanks for writing this! Finally a primer we can send to all of our friends

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right, this is why i wrote this. i doubt i'll write about epigenetics again unless there is an evolutionary angle

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Someone give this man a University Chair and a megaphone. Thank you very much for this essay, Razib; and Happy Holidays to you and your family.

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Dec 19, 2022Liked by Razib Khan

Great work Razib. I shared this in all those groups where this should he shared. (You know the ones I am talking about)

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I agree that the pop-psychology stuff is mostly pseudoscience, but have all of the possible mechanisms of epigenetic inheritance really been disproven? Even if the DNA structure is wiped clean of markers during meiosis and fertilization, that doesn't seem to rule out other possible non-DNA mechanisms of inheritance, like small noncoding RNAs.

I'm just wondering because I found this review paper making the case for some forms of epigenetic inheritance:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521963

It didn't strike me as pseudoscientific, so I tried following the citations and couldn't really find any obvious problems with them.

For example, this paper has a clever mouse experiment showing that daughter mice that had identical DNA sequences differed from each other based on their father's Y chromosome (which they did NOT inherit):

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4045629/

and the authors speculate that this could be due to inheritance of methylation patterns, histone modifications, or noncoding RNA.

Anyway I agree that epigenetic inheritance is largely unproven, but I'm not sure if it has been disproven.

EDIT -- This preprint appears to be a negative replication of the mouse experiment I was talking about. I haven't read through the whole thing yet, but it looks like they did a similar experiment and didn't find any transgenerational epigenetic effects:

https://www.biorxiv.org/content/10.1101/2022.12.23.521797v1?rss=1

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This is a review paper with notably thin empirical examples of epigenetic transmission. The mouse study, as I read it, does not require epigenetic processes because a gene is spliced out and replaced. The paper has a kind of void core, rich in speculation and short on evidence.

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Jan 10, 2023·edited Jan 10, 2023

This is an excellent post; the popular conception of epigenetic inheritance is deeply flawed and I hope this helps to correct it.

In case anyone wants to dive deeper into the biology behind this, I've written a three-part epigenetics series here:

1. https://denovo.substack.com/p/what-is-epigenetics

2. https://denovo.substack.com/p/epigenetics-of-the-mammalian-germline

3. https://denovo.substack.com/p/epigenetic-inheritance-in-mammals

(I am a researcher specializing in human reproductive development.)

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founding

Razib: Thank you very much for a clear explanation of a very murky subject.

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“For a single biochemical and developmental pathway, DNA supplies the orchestra musicians in the form of genes, while epigenetics plays conductor, bringing them together to summon a complex symphony of mechanisms and structures from the sequence of interacting chemicals.” The DNA (the musicians) is inherited from the parents; where do the epigenetics (the conductor) come from? Are the epigenetics partly inherited, partly affected by the environment—with, on your account, the latter effect being minuscule?

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if a developmental geneticist is reading this please answer.

yes, i learned the setting of marks once but i kind of forgot. development is not interesting to me :)

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Dec 20, 2022·edited Dec 20, 2022

Your description of the germline reprogramming is apt here. While the maternal and paternal genomes are inherited in the germlines, the germline epigenetic marks are largely erased in the zygote (although not absolutely, which is how there's thought to be a capacity for epigenetic inheritance to a weak and labile degree), and a new process of diffusible morphogen gradient-mediated differential gene expression starts occurring in the developing multicellular embryo until certain lineage identities are formed. The cell lineage-specific epigenetic marks are a consequence of this transcription factor-dependent process, but then also serve to maintain cell identity during tissue expansion and maintenance due to the semi-conservative nature of modified histone segregation during mitosis.

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Absolutely loved this.

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founding

I agree, the importance of alerting the world that fake news overtly distorts scientific knowledge cannot be overemphasized.

To help people understand the issue better, some popular science articles on epigenetics, particularly about homosexuality, have been bookmarked below, with summaries provided. However, it seems that research on these topics has been censored, is simply not being published, or society lost interest since the invention of gay marriage by Obama. However I don't think the the majority of the world's population has lost interest yet simply because of top down censorship of a few corrupt liberals, and most people are still looking for truth.

What is being suggested here is that epigenetics is a fundamental filter of perception and behavior:

https://www.wsj.com/articles/research-finds-genetic-links-to-same-sex-behavior-11567101661

Summary: A study published in the journal Science has found evidence of a genetic link to same-sex behavior. The research analyzed genetic data and survey responses from almost 500,000 people, and found that genetic factors could account for between 8% and 25% of same-sex sexual behavior. The study's authors cautioned that the results do not indicate that same-sex behavior is solely determined by genetics, and that environmental and social factors are also important. The findings could have implications for the understanding of the biology of sexuality and for the treatment of LGBT individuals.

https://www.science.org/content/article/homosexuality-may-be-caused-chemical-modifications-dna-rev2

Summary: A study of male twins by Eric Vilain's lab at the University of California suggests that epigenetic effects, chemical modifications of the human genome that alter gene activity without changing the DNA sequence, may have a major influence on sexual orientation. His team identified five regions in the genome where the methylation pattern appears closely linked to sexual orientation, and the results astonishingly predict sexual orientation with almost 70% accuracy. The research is still preliminary and based on a small sample, so it must be replicated with more twins to be fully credible.

https://link.springer.com/article/10.1007/s00439-004-1241-4

This study goes beyond epigenetics and is the first to report a full genome scan of sexual orientation in men. The researchers analyzed the genetic information of 456 individuals from 146 families with two or more gay brothers. They found evidence of genetic links to sexual orientation in three regions of the genome: 7q36, 8p12, and 10q26. The highest score was found near D7S798 in 7q36, with approximately equal contributions from both parents. The second-highest score was located near D8S505 in 8p12, also with equal maternal and paternal contributions. A maternal effect was found near marker D10S217 in 10q26, with no paternal contribution. The study did not find a linkage to Xq28 in the full sample, but further analysis showed a high score in that region in previously reported data.

https://medicalxpress.com/news/2019-09-scientists-hormone-potentially-linked-hypersexual.html

A study conducted by researchers from Uppsala University and Karolinska Institutet in Sweden has identified epigenetic changes associated with hypersexual disorder, a recognised compulsive sexual behaviour disorder, which affects around 3-6% of the population. If you think about it, that is a lot of people, even though it sounds insignificant. The scientists examined DNA methylation patterns in the blood from 60 patients with hypersexual disorder and compared them to samples from 33 healthy volunteers. Their results showed that changes to DNA methylation affected the function of genes involved in the regulation of the hormone oxytocin, potentially leading to elevated levels of the hormone. The authors of the study suggest that these findings could offer a new angle for the treatment of hypersexual disorder.

I live in Portland which has very high levels of drug abuse, particularly tweekers, leading to concerning behaviors, such as a previously straight man engaging in homosexual activity and another man arrested for his interactions with underage girls on dating apps. While I cannot confirm that meth was the only drug in question, these cases were definitely right after they became meth addicts. So meth, can make men gay, or even pedophiles. This topic I think is worth further investigation particularly on a physiological level.

I also think that Section 230 of the Communications Decency Act is very dangerous. As the historic Twitter Files revealed that Twitter simply allowed child pornography until Elon Musk took it over and began shutting down the promoters of child pornography. It is now up to individuals to enforce the law, as we see with the lawfare revolution to oust the prior administration. I left Twitter the moment I realized they are demolishing a sitting POTUS, so did many poets who were the first Twitter users. The censorship of Donald Trump was clearly a monumental crime, which utterly destroyed trust worldwide, and certainly an attack on science, driving scientists out of public life due to mistrust. I suspect that pedophilia is vastly more prevalent in the US that many realize, particularly in families that have gay "parent" overlords. This issue may be partially driven by drugs and poorly regulated dating apps. I have reached these conclusions through careful consideration and analysis. If you are not even allowed to even say something, how can you possibly address the issue? That is why I am very grateful to Elon Musk.

The epigenetics of poverty:

https://www.sciencedaily.com/releases/2019/04/190404135433.htm#:~:text=of%20the%20genome.-,They%20discovered%20that%20lower%20socioeconomic%20status%20is%20associated%20with%20levels,the%20genes%20in%20the%20genome.

Summary: Basically this study has found that poverty is associated with levels of DNA methylation at more than 2,500 sites, across more than 1,500 genes. DNA methylation is a key epigenetic mark that has the potential to shape gene expression, and poverty appears to leave a mark on nearly 10% of the genes in the genome. The study suggests that DNA methylation may play an important role in shaping the biology and health outcomes affected by socioeconomic status. The study's lead author, Professor Thomas McDade, claims the findings highlight a potential mechanism through which poverty can have a lasting impact on a wide range of physiological systems and processes. The scientists will now focus on determining the health consequences of differential methylation at the sites they identified, and many of the genes are associated with immune responses to infections, skeletal development, and development of the nervous system.

https://phys.org/news/2013-07-climbing-social-ladder-strongly-grandparents.html

Summary: This study shows that the social class of a person's grandparents has a significant impact on their social mobility, even after considering the influence of parents. The study found that grandchildren with grandparents in professional-managerial positions are at least two and a half times more likely to go into similar occupations compared to those with grandparents in unskilled manual occupations. The research, which used data from over 17,000 Britons born in 1946, 1958, and 1970, reveals that social advantages and disadvantages are more persistent across generations than previously thought. The study suggests that the "grandparents' effect" may work through wealth and property inheritance, and further research is needed to determine the precise mechanisms.

https://medicalxpress.com/news/2023-02-prairie-voles-born-c-section-bond.html

Scientists from the University of Virginia (UVA) have discovered that prairie voles, which are famous for their tendency to mate for life, do not form the same pair bonds if born by C-section. The research was carried out by Allison Perkeybile and Sue Carter of UVA's Department of Psychology. Carter is responsible for pioneering the use of prairie voles as a research model and for discovering the relationship between oxytocin and social monogamy. The researchers found that if an emergency dose of oxytocin was given after birth, the voles were still able to form pair bonds. The study raises the question of whether the way humans are born can affect their ability to love and relate.

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Is the molecular biological machinery for high (or low) fidelity transmission of epigenetic markers down generations of cell lines well know? I've read (well the first 1/4 anyways) of many papers in DNA replication about the complex molecular mechanisms that drive this. However, I don't think I've ever seen anything on how epigenetic markers are passed along. It seems like this would require complex machinery, the mastery of which would have great, great biomedical utility...

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a lot of epigenetic research is funded and aimed to cancer.

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