How Modern Biology Is Rewriting Our Understanding of Genetics, Disease, and Inheritance
By: Nessa Carey
Epigenetics refers to external modifications of DNA that regulate the expression of genes, turning them “on” or “off.” While the DNA sequence doesn’t change, the external modifications affect how the genes are read.
Epigenetic mechanisms help explain:
- Why you can have identical genotypes but different phenotypes (twins).
- Why an event continues to influence an organism long after the event occurred.
The epigenome is the immediate cellular surroundings, the presence or lack of certain enzymes, proteins, that modulates the level of gene expression over time.
There are two main mechanisms that help to regulate the level of expression of a gene: methylation and histone modifications.
In DNA methylation, the addition of a methyl group to DNA prevents certain genes from being expressed. While the gene’s molecular make-up may change, it is not mutated. The attachment of the methyl group is driven by the lack or presence of certain enzymes or proteins.
In histone modifications, the presence or absence of histones (proteins that DNA wraps around), inside or around the genes, regulates their expression.
As cells divide, these DNA modifications are preserved in the new cell. As two strands of DNA separate to form two new cells, in the new cell, the single strand of DNA is copied and similar epigenetic changes are applied.
As cells continue to grow and divide, epigenetic marks become more complicated, explaining how and why cells with identical DNA are able to differentiate over time. Genes are expressed differently as cells roll down Waddington’s landscape.
All of this mostly concerns the expression of genes within the organism over time. For the most part epigenetic changes are not inherited. The germ cells that form a new organism typically are completely reset and lose all their epigenetic marks.
Therefore, trans-generational inheritance happens rarely. However, the impact of certain toxins on the epigenome has been known to survive the germ cell reset. In other rare cases, epigenetic changes caused by malnourishment also survived multiple generations.
Informative, a good primer on the concept, but not an easy read. A lot of the concepts are unavoidably technical, especially when there is a need to go through and explain complex molecular biology.
The most interesting parts of the book deal describe cellular development, stem cells, gender differences, and applications of epigenetics in medicine (cancer treatments) and ageing.
The field of epigenetics is still in its infancy. It seems relative certain that changes in the environment can drive the epigenetic regulation of gene expression and cause persistent, long lasting changes in areas that we care about. What is less clear at this point is if there is any inheritance of such epigenetic changes (acquired phenotypes) from one generation to the next. While it seems to be extremely rare, some examples observed (the Dutch Hunger Winter, cited in this book as well) are quoted quite often and make it sound as if epigenetic inheritance is the norm and more common than it actually seems to be.