In case you didn’t see, I have a post on epigenetics up, You can’t take it with you: straight talk about epigenetics and intergenerational trauma, which will probably be my last word on this. But coincidentally, this preprint came out, Lack of evidence supporting transgenerational effects of non-transmitted paternal alleles on the murine transcriptome:
Transgenerational genetic effects are defined as the effects of untransmitted parental alleles on the phenotype of their offspring. Well-known transgenerational genetic effects, in humans and other mammals, are the effects of a parental genotype on the nurturing ability of the parents, coined “genetic nurture”. However, there exist examples of transgenerational genetic effects in model organisms that are independent of nurturing effects and support the epigenetic transmission of a memory of the parental genotype possibly mediated by small RNA species. To test whether such transgenerational epigenetic effects might exist in mammals, we generated 833 isogenic C57BL/6J (B6) mice that differed only by the presence in the genome of their sire of one copy of four A/J chromosomes (MMU 15, 17, 19 or X). We measured 25 anatomical traits and performed RNA-Seq on five distinct tissues (heart, liver, pituitary, whole embryo, and placenta). There was no evidence of a significant effect from untransmitted A/J sire chromosome alleles, whether on anatomical traits or gene expression level. We observed an effect on Mid1 expression levels in multiple tissues, but this was shown to be due to a de novo mutation that occurred in one of the sire lines. We conclude that transgenerational epigenetic memory of non-transmitted paternal alleles – if it exists – is uncommon in mice and likely other mammals.
I didn’t want to get into a mud-slinging contest, but a lot of people in epigenetics are pretty skeptical of a lot of the work that’s published that shows inter-generational transmission of any sort in animals.
I thought the substack was very good. Almost understandable by a non-biologist such as I. To me the key take away was:
“In mammals (as in most vertebrates) the most basic reason transgenerational epigenetic transmission of anything particularly significant seems unlikely is the fact of a “factory reset” of the epigenetic marks during meiosis when sperm and egg are created, and a second one right after fertilization, when sperm and egg fuse to produce the zygote. In contrast, in mitosis, all conventional, non-reproductive cellular replication that does not that lead to sperm and egg cells, the pre-customized histones are usually duplicated, and their epigenetic marks are transmitted to the new copies. DNA or histone methylation can also be inherited through the cellular division process. But this is constrained to the life cycle of the individual. The marks are erased and the epigenetic instructions routinely reset and wiped clean early on in embryogenesis, as the single fertilized egg develops into a highly differentiated and complex fetus and then a child.”
If I read that rightly, mammals are subject to the great reset by the fertilization and growth process, and there is no epigenetic trans-generational mechanism.
The Ikea example was fantastic, as was the 2nd diagram (about Intergenerational Epigenetic Transmission).
One thing that I think needs to be stressed for non-biologists — perhaps especially us older non-biologists — is that genes/genetics/DNA is not solely, probably not even primarily, about inheritance. Most of us first heard about DNA in that context, and for those of us who never got beyond Bio 101, we never learned that genes are central to the moment-to-moment functioning of the cell. That may sound pretty ignorant to those who actually know something about cell biology/molecular biology — along the lines of “D’oh! What do you think genes do?”, but it’s true.
It is something that I realized only 5-10 years back from reading this and one or 2 other bio blogs (Zimmer, not sure what else). I finally realized that genes direct the cell’s response to conditions/stimuli. In utero (for mammals, anyway), the result is embryonic development. After birth, the result is metabolism.
But biology, at least a half-century ago when I was in HS and college, this wasn’t at all obvious to the student. DNA/genes were covered only in the context of inheritance and evolution.
Anyway, with this knowledge in hand, it is obvious that a lot else must be going on with epigenetics than Lamarkian inheritance, and the 2 examples I complimented above make that very clear.