How Your Great Grandmother’s Habits Could’ve Altered Your Genes
Your grandmother's lifestyle when she was younger could be responsible for changes in your gene expression and your characteristics to this day. For example, you may be more likely to have clinical depression if your grandmother was neglected as a child. You may also have a predisposition for type 2 diabetes, metabolic disorders, or obesity if your grandmother or even great grandmother grew up during a famine while she was pregnant with your mother or father.
How can your genes be altered? One word: Epigenetics. Epi meaning ‘on top’ and genetics referring to the genome. DNA is more than just a string of bases, A, T, C, and G, wound into a double-helix structure. On top of these nitrogenous bases, epigenetic markers tell the gene if they can be turned on or off.
A common form of epigenetic modification is DNA methylation, this involves the removal or addition of the methyl group (CH3) on the base cytosine by enzymes called DNA methyltransferases. The genetic code itself remains the same, but the presence of the methyl group can prevent the transcription factor from binding onto the gene, and therefore the gene cannot be expressed (in other words, the gene is switched off).
Another form of epigenetic modification is histone modification. In the nucleus, DNA is found wrapped around histone proteins forming nucleosomes that form coils, supercoils, and eventually a condensed structure called a chromosome. The modification of the positively charged histone tail by methylation, phosphorylation, acetylation, or ubiquitination changes the charge of the tail.
The charge affects how tightly or loosely the DNA is wrapped around the histone proteins. The more tightly wrapped the DNA is around the histones the less accessible the DNA is for transcription factors and other proteins to transcribe the gene, thus switching the gene off.
Just over a decade ago, it was believed that the slate got wiped clean and epigenetic markers were removed and only the genetic code got passed on from parent to offspring. However, scientists have now realized that this is not the case and the epigenetic markers one acquires throughout their life can be passed on from generation to generation. This essentially means that your great-great-grandmother’s smoking habits could have changed the way your genes are expressed and result in phenotypic differences that can be seen even today!
Rehan et al. 2012 conducted a study using rat models to demonstrate the effects of nicotine smoke during pregnancy on second-generation offspring. The results showed that nicotine exposure affected epigenetic markers on important genes involved in lung formation and increased the likelihood of the offspring developing asthma. This effect was proven to be multigenerational which may also explain the increase in asthma cases in children. Other studies also show smoking can result in epigenetic modifications in the germline which can pass onto subsequent generations.
“The pulmonary effects of nicotine exposure during pregnancy are not restricted only to the offspring of the exposed pregnancy but are also transmitted to subsequent generation”
Scientists have studied historically famous famines and the DNA of grandchildren whose grandparents lived during this time. The Dutch hunger famine occurred during the end of World War II and lasted for 6 months. Food supplies were cut as Nazi’s punished the Netherlands for their railway workers striking as an attempt to prevent travelling Nazi troops.
The Dutch hunger famine provided a unique opportunity for scientists to study the effect of starvation on genes and how this can pass onto offspring. During the famine, mothers who were pregnant gave birth to babies who had an increased risk of developing obesity, diabetes, and even mental disorders such as schizophrenia. Evidence shows that starvation altered epigenetic markers i.e. methyl groups on metabolic genes.
Tobi et al. 2018, studied one of these genes, PIM3, which is responsible for energy metabolism. He found a link between a methyl group on PIM3 and a high body mass index in individuals who were once in-utero at the time of the famine. Silencing PIM3 slows down metabolism, which at the time of the famine, could be helpful for the pregnant mother. However, these epigenetic modifications are passed onto the offspring who may grow up having a normal diet but as they still have this permanent alteration to their gene, their body cannot burn fat as fast, so they put on more weight leading to obesity.
It is quite phenomenal to think that the environment and the factors your ancestors were exposed to could be responsible for your likelihood to develop schizophrenia, depression, obesity, and more. Perhaps now, you may want to think twice before you pick up your cigarette or stuff your face in a pack of doughnuts as it may be your great-grandchildren who will end up paying the price!
