Why Your Genes Are Not Your Destiny
By: Nita Jain
Tags: Health, Education, Science, Ideas, Self Improvement

What is epigenetics?

When most people think of evolution, the first name that comes to mind is Charles Darwin, but a contemporary of Darwin’s named Jean Baptiste Lamarck had proposed a theory of “acquired characteristics” by which individuals evolved certain traits within their lifetimes. The most oft-cited example discrediting this theory is that of giraffes elongating their necks by stretching to reach the treetops and then passing on this trait of long necks to their progeny. In contrast, Darwin proposed that those giraffes that had the longest necks went on to find food, survive, and reproduce. Eventually, Darwin’s theory of natural selection prevailed, but his 18th century French naturalist contender may have simply foreseen the field of epigenetics, the study of those drivers of gene expression that occur without a change in DNA sequence. The prefix “epi-” means above in Greek, and epigenetic changes determine whether genes are switched on or off and also influence the production of proteins. If you imagine your genetic code as the hardware of a computer, epigenetics is the software that runs on top and controls the operation of the hardware.

Epigenetic changes control the expression of genes through various mechanisms. The epigenetic mechanism of DNA methylation involves tagging DNA bases with methyl groups, a process that tends to silence genes. DNA methylation is responsible for X-chromosome inactivation in females, a process necessary to ensure that females don’t produce twice the number of X-chromosome gene products as males. Methylation is also responsible for the normal suppression of many genes in somatic cells, allowing for cell differentiation. Every somatic cell in the human body contains nearly identical genetic material, but skin cells, muscle cells, bone cells, and nerve cells exhibit different properties due to different sets of genes being turned on or off.

Methylation of cytosine bases leads to changes in gene expression. Mariuswalter [CC BY-SA 4.0]

Many epigenetic changes associated with the development of cancer have been found to be transgenerational; in other words, the altered epigenetic pattern can be passed down to subsequent generations without re-exposure to the agent that originally caused the epigenetic change. The effects of treatments, such as radiation and chemotherapy, and environmental toxins, such as endocrine disruptors, are often transmitted to offspring via reprogramming of DNA methylation patterns.

Inappropriate DNA methylation has been referred to as a “hallmark of cancer,” along with uncontrolled cell growth/proliferation. Almost all types of human tumors are characterized by two distinct phenomena: global hypomethylation or loss of methylation, which may result in the expression of normally suppressed oncogenes, genes that promote tumor formation, as well as regional hypermethylation or increased methylation near tumor suppressor genes. In other words, genes that promote tumor formation are turned on while genes that suppress tumor formation are turned off.

Cigarette smoke has been shown to promote both demethylation of metastatic genes in lung cancer cells as well as regional methylation of other specific genes via modulation of enzymatic activities. To succinctly summarize, genes themselves are not driving tumor formation; rather inappropriate gene expression is increasing the risk of tumor development.

National Human Genome Research Institute (NHGRI) from Bethesda, MD, USA [CC BY 2.0]

Considering DNA methylation’s crucial role in regulating health and disease, insights gleamed from genetic models devoid of DNA methylation may not be relevant to the human condition. Epigenetic changes tend to be species-specific; the yeast Saccharomyces cerevisiae and the roundworm Caenorhabditis elegans don’t seem to exhibit DNA methylation at all, and the fruit fly Drosophila melanogaster displays only a minimal amount.

A 2018 study conducted on the nematode C. elegans concluded that the continual expression of genes responsible for developmental growth contributed to aging in later life; the authors argued the results could also be applied to humans. However, DNA methylation is widely prevalent in human genomes and responsible for gene suppression at different stages of development, which could prevent the unnecessary gene expression described in the study.

Using models that are subject to similar epigenetic changes is critical when attempting to extrapolate findings to humans. As previously suggested, our attempts to unravel the interface between genes and disease without accounting for genetic expression may therefore lead to incomplete or inaccurate models of disease and aging.