Dive into Epigenetics: how Monozygotic Twins raised in different environments can have different gene expressions

All cells in your body carry the same 23 pairs of chromosomes. So why does one become an epithelial cell and the other an adipocyte? The answer lies within Epigenetics; first defined in the 1940s by Conrad Waddington as “the branch of biology which studies the causal interactions between genes and their products which bring the phenotype into being.’’ Epigenetics is now understood as ‘‘the study of changes in gene function that are mitotically and/or meiotically heritable and that do not entail a change in DNA sequence.”

Epigenetics covers an array of mechanisms, including DNA methylation- the addition of a methyl group to the 5’ position of cytosine residues, generally associated with transcriptional silencing. Another major mechanism is histone modification, encompassing processes such as histone methylation, which often represses gene activity, and histone acetylation, which typically promotes transcription by loosening the chromatin structure. These processes allow for the fine-tuning of the genome, enabling differentiation; however, inaccuracies in inheritance have been linked to disease progression and development.

Monozygotic (MZ) twins have become powerful models in this field. Despite sharing an identical genome, they often display distinct phenotypes, exhibiting disease discordance rates frequently exceeding 50%. This demonstrates that genetic predisposition alone cannot explain the entire phenotype, highlighting the role of epigenetic regulation. Discordance trends have also been seen to be more pronounced in rare diseases, reaching 80% in rheumatoid arthritis and schizophrenia, emphasizing how small chemical changes can have an immense effect on disease progression.

Over the past two decades, the discordant twin model has provided unique insights into risk factors shaped by both lifestyle and environmental factors. Early epigenetic MZ twin studies identified DNA methylation differences in specific genes. For instance, DRD2, a dopamine receptor gene found in schizophrenia, which showed greater methylation differences in discordant twins than in unrelated cases. Similar findings emerged in bipolar disorder and caudal duplication anomaly.

More recently, genome-wide methylation studies in autoimmune diseases examined 15 twin pairs with lupus, rheumatoid arthritis, and dermatomyositis. They identified 49 significantly differentially methylated regions in lupus, involving immune-related genes- though no differences were observed in RA or dermatomyositis.

Overall, Epigenetics has proved to play a large role in phenotype distinction and disease progression; however, a lot is yet to be fully understood, proving it to be an area of high interest and development.