14 May, 2012, Lux Fatimathas
From the early days of Mendel and his peas, through 200 years of discovery leading to the Human Genome Project, genetics has changed the landscape of science, medicine and society. It led to the common belief that the genetic code was the sole means of imparting the instructions that shape life and pass on traits through the generations.
Epigenetics has, however, revealed how the seemingly ‘hard-wired’ genetic instructions of the genome can be tweaked by chemical modifications that leave the DNA sequence itself unchanged. Moreover, diet, drugs and lifestyle have all been shown to affect these epigenetic modifications.[frax09alpha]
The human genome contains around 30,000 genes, with each gene imparting specific instructions to a cell on what to become and how to behave. But how can a single cell know what to do if it is on the receiving end of thousands of competing instructions?
The answer lies in epigenetics and its ability to switch genes on or off by imposing chemical modifications upon the DNA or the proteins that package DNA. These modifications, such as DNA methylation, transform the cacophony of competing genetic commands into a harmonious chorus of instructions, specific to each individual cell.
A visually striking example of epigenetics at play can be seen in the multicoloured agouti mice.
Agouti mice carrying the same agouti gene can be surprisingly different in appearance and health depending on how methylated this gene is. High methylation turns the gene off, resulting in healthy, trim, brown mice, whilst low methylation produces obese, yellow mice. Remarkably, a simple change in the diet of pregnant agouti mothers can increase methylation of this gene in her offspring, resulting in litters of predominantly healthy, brown mice.
Increased methylation, as in the brown agouti mice, is however not always beneficial. The genome contains numerous genes that prevent the growth of tumours. Flicking the off switch for these genes, through too much methylation, can allow cancer to take hold. In recent years steps have been taken towards translating this newfound knowledge into viable therapies, with several epigenetic drugs targeting cancer now on the market.
Growing interest in epigenetic therapies for disease highlights the importance of epigenetics in keeping our bodies in check.
New insights suggest our genes may have an epigenetic memory, which could also impact the health of our descendents. Take for example studies of the isolated community of Overkalix in Sweden. Overkalix grandfathers who experienced acute periods of feasting during times when food was otherwise scarce, were shown to have grandsons more prone to diabetes. Epigenetic changes are proposed as the potential culprit. This raises the possibility that our experiences today could echo through the generations to affect our grandchildren.
In the age-old debate of nature versus nuture, epigenetics bridges the divide between these two opponents, demonstrating how nuture can work through nature. With our epigenetic heritage shaping up to be more labile than we expected, understanding the epigenome will prove more important than ever in shaping the scientific and social landscape ahead of us.
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