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In a documentary, they were saying that epigenetics changes caused by the environment in an individual can be transferred to the following generations. I have some questions on that:

  1. How many generations are affected by an epigenetic change? can this be permanent?

  2. Can drugs cause epigenetics changes in the current population that are visible in the following generations in the form of disease and birth defects?

  3. Do epigenetic play any role in evolution? For example, is it possible that an epigenetic change becomes a permanent genetic change after a certain number of generations?

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    $\begingroup$ You may not be aware that you have stepped into a minefield. The term epigenetics has been subject to considerable hype (I would be interested to know what documentary you watched and what precisely was claimed), phenomena in insects extrapolated to humans, and association confused with causation. In order to separate fact from fiction here, one needs to be able to understand the basic science. Do you have the background to understand this article, for example. $\endgroup$ – David Aug 20 '20 at 17:41
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Generally speaking, epigenetic modifications are not inherited as they are reset during embryogenesis. However, subsequent epigenetic modifications can be acquired during the period of pregnancy, which as a mechanism depends on the epigenetic state before the reset and on the physiological conditions of the mother including nutrition, health, stress, etc.. Obviously drug-intake years before pregnancy can still affect the mothers health-state.

Answering your first question: Epigenetic modifications generally cannot be directly passed, but indirect effects could theoretically pass through multiple generations without hard limit.

A major barrier to transgenerational epigenetic inheritance is germline reprogramming, during which histone variants and their modifications, as well as small RNAs and DNA methylation, are all reset. In mammals reprogramming occurs both in the germline and in the zygote immediately after fertilization. (Source: Heard & Martienssen 2014 doi: 10.1016/j.cell.2014.02.045)

2: The great potato famine is said to still have epigenetic effects, generations later. 3.: Epigenetic changes cannot directly "become permanent" as genetic changes, although hypothetically speaking, epigenetic states can lead to viability of certain mutations that would otherwise be lethal and can therefore in theory influence evolution.

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    $\begingroup$ "Epigenetic modifications cannot be directly passed" seems to be a bit of a controversial statement, as far as I know (as is the converse, that they can be directly passed), especially for humans. If you want to make that claim, it needs a reputable citation to back it up. $\endgroup$ – Bryan Krause Aug 20 '20 at 16:30
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    $\begingroup$ I agree, I added a source. Sorry! What I meant is that modifications are at first removed but then partly could be restored later. So it's not "direct". Given question 3 implies that the OP is no biologist, I didn't want to unnecessarily complicate things. $\endgroup$ – KaPy3141 Aug 20 '20 at 16:57
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    $\begingroup$ I think it would be helpful to be more specific about what "epigenetic modifications/changes" are. People tend to fixate on methylation/histones, but there are perfectly good epigenetic circuits set up that are based only on transcription factors/protein components. The heritability of the different kinds, that's a different question. $\endgroup$ – Maximilian Press Aug 20 '20 at 17:01
  • $\begingroup$ Much better. Thanks! The word "generally" adds a lot, too. I've made some edits to include the author names and made the DOI a link. $\endgroup$ – Bryan Krause Aug 20 '20 at 17:01
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Epigenetic changes can only be passed directly onto the next generation when they occur in the cells that proliferate into the gametic cells (ovum and sperm cells).

There is some research with rat models that show the inheritance of epigenetic changes over several generations, so it´s possible.

(an example for cocaine-addiction: https://www.nature.com/articles/nn.3280)

The main protein family that participate in epigenetic regulation are the histone deacetylases (HDACs) and the histone acetyltransferases (HATs), which can modify proteins that bind to the DNA and thus control the expression and activity of genes, and these proteins can be influenced by environmental changes.

(Several types of cancer are thought to be caused/affected by the activity of HDACs that shut down tumor suppressor genes, and there are many medical studies focusing on chemotherapeutically inhibiting their function in cancer patients.)

This paper can give you a good overview: https://pubmed.ncbi.nlm.nih.gov/11420732/

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Question 1: how many generations.

In one of the first description of transgenerational epigenetic inheritance, before any of the mechanisms were worked out, Woltereck found (my translation, caveat emptor) that he could find influences on both children and grandchildren of starvation in Daphnia (Figure 1).

enter image description here

Figure 1. Daphnia head morphology response to starvation. Left: control animal (fed normally, parents and grandparents fed normally). Right: successive generations of descendants of starved animals. 1. Gen: child, 2. Gen: grandchild, 3. Gen: great-grandchild.

How common such epigenetic changes are is a huge subject of debate. Nutrition appears to be the big one- see also the Barker hypothesis in humans, especially in re: the Dutch Hunger Winter.

Question 2: don't know.

Question 3:

It's a thorny question! Woltereck and similar people were already arguing about whether these observations might be evidence for Lamarckian inheritance, e.g. inheritance of acquired characteristics. We've pretty much gotten rid of Lamarckian inheritance in favor of vanilla Darwinian inheritance via DNA, but people still argue about it, as e.g. here.

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