Epigenetic Changes Can Cause Developmental Abnormalities In “Grandoffspring” As Well As Offspring

Our physical traits and risk of disease can be determined by epigenetic modifications that alter the way our genes are expressed, meaning our health and development can vary from what is set in our genetic code. Whether these changes could be transmitted across generations has been a puzzling question, but new research believes it has found evidence of “transgenerational epigenetic inheritance” in roundworm offspring.

Research took the roundworm Caenorhabditis elegans (made famous by doing a lot of research and causing considerable beef on Twitter) and stripped the chromosomes contained in their sperm from a histone protein that alters the packaging of DNA. The histone tag, known in the industry as H3K27me3, is found in all multicellular animals and is able to turn off the functions of genes by cramming DNA so tightly into chromosomes that not all regions are accessible for activation.

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The Treated C. elegans Sperm were then used to create offspring, which the study researchers could look for signs of abnormal gene expression in. Their observations showed that genes inherited from sperm, known as paternal chromosomes, were turned on as a result of the lack of H3K27me3 histone marking, causing tissues to form cell types that they would not normally form.

Tissues that should normally be engaged in the production of sex cells showed genes that one would expect to find in nerve tissue, for example. The mix-up occurred in all of the tissues the team analyzed, but depending on the tissue examined, different genes in different samples were turned on inappropriately.

Furthermore, the effect was not only seen in the chromosomes of the first generation of offspring that emerged from the histone-depleted sperm. It also showed up in the next generation or the “grandchildren” in different ways.

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“In the germline of the offspring, some genes were activated incorrectly and remained in the state without the repressive mark, while the rest of the genome regained the mark, and this pattern was passed on to the grandchildren,” said corresponding author Susan Strome, professor emeritus of Molecular, Cellular and Developmental Biology at UC Santa Cruz, in a statement. “We speculate that if this pattern of DNA packaging is maintained in the germline, it could potentially be passed through numerous generations.”

C. elegans are often used as a model for wider research due to their suitability for research (when trying to make repeated observations, many transparent objects pay off with low maintenance costs and a short lifespan). However, they are still not human, which means that what we learn from them may not necessarily apply to our own biology.

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However, Strome is hopeful that similar findings from mammalian cell research might suggest that this type of transgenerational epigenetic inheritance might occur in the bodies of other species (although these studies in particular found no evidence to support this). If so, it could provide an explanation of how a person’s health and development can be influenced by their grandparents, but also by their parents.

“This looks like a conserved trait of gene expression and development in animals, not just a weird worm-specific phenomenon,” Strome said. “We can do amazing genetic experiments C. elegans This is not possible in humans, and the results of our experiments with worms can have far-reaching implications for other organisms.”

This research was published in Proceedings of the National Academy of Sciences.