Epigenetics: where nature and nurture collide

The nature vs. nurture debate looks at whether our genes or our relationship to our environment have a greater impact on our physical and emotional development.  While this is normally a term used by psychologists studying human nature, there are also implications at the molecular biology level, and is referred to as epigenetics.  

Epigenetics is a really interesting concept because it kind of supports Lamarck's ideas on evolution, which when I was going through my early training as a biologist, was generally accepted to be laughably wrong.  Lamarckism is the idea that the diversity of life was caused by physical adaptation to an environment that was then passed on to offspring.  It was comically compared to Darwin's theory of evolution using giraffes as an example.  According to both Darwin and Lamarck, giraffes used to have short necks. Lamarckism explains the evolution of long necks being caused by giraffes needing to stretch their necks to reach the higher branches, which strengthened and stretched their necks, and their offspring inherited these traits.  This is known as "soft inheritance", and always reminded me of a good Chuck Norris joke.  Darwin would have explained giraffes' long necks as variations in DNA sequence that led to longer necks.  We know DNA is inherited, so it was the more generally accepted concept.  Of course, the evolution of giraffes' necks is far more complicated than both naturalists thought. 

Anyway, the point is, epigenetics has been making a come-back.  Epigenetics is used to describe changes that are made to the expression of genes (the copying, or transcription of genes into RNA and the subsequent translation of the RNA into proteins) that do not involve changes to the DNA sequence itself.  This can be done by a whole host of really interesting mechanisms.  One really interesting mechanism is chromatin remodeling.  Chromatin is the combination of DNA and DNA-associated proteins that are found in cell nuclei.  Here's a pretty good picture of what that looks like:

Chromatin remodeling works by rearranging those proteins so that some genes are more or less accessible, depending on their function.  So basically, if you're exposed to a stressful environment, your chromatin might rearrange to make sure that genes that are involved in dealing with stress are more accessible to be copied into RNA and expressed as proteins, than genes that might not be so useful.  Chromatin remodeling can be done through a whole host of processes, but the one I'll focus on is the addition of a methyl group to two of the four bases that makes up DNA.  This is called DNA methylation.

A huge amount of human disorders are actually determined by DNA methylation and epigenetics as a whole, especially during fetal development.  Epigenetics influences obesity, cancer development, susceptibility to cardiovascular disease and diabetes, and genetic disorders like Prader-Willi syndrome.  And a lot of the epigenetic effects that humans encounter occur in utero.  In particular, maternal diet during pregnancy can have a significant effect on which genes are expressed and which aren't.  Maternal health and environment clearly has HUGE implications for public health (cough *listen up government* cough).  For example, maternal folic acid intake is involved in the normal neural tube development in fetuses.  In fact, it's so important, that most Canadian wheat and pasta is fortified with folic acid to avoid developmental defects. 

I found two recent(ish) studies that looked at the epigenetic effect of diet.  One study put pregnant mice on diets with varying protein levels and types, and then looked at the level of DNA methylation in the offspring and how this might affect physiology and metabolism.  What the authors found is that low protein diets (a stressful environment) during pregnancy led to offspring with significantly disturbed gene expression in their livers.  And it wasn't just genes specifically involved with protein metabolism that were affected, these were genome-wide alterations to gene expression in liver cells.

The second study looked at exposure to plastic-derived environmental compounds, like BPA, and their epigenetic effects on offspring.  Female rats were exposed to different plastic-derived compounds, then bred.  Offspring three generations later (referred to as F3 in science jargon) had higher rates of obesity, and uterine or testical disease.  That means that the exposure of female rats to BPA affected their great-grandchildren!  That's because exposure to BPA and other endocrine disrupters causes alterations in DNA methylation which is then inherited by offspring and passed on to subsequent generations.

Epigenetics is a cool way in which scientists are able to look at the ways in which our interactions with our environment, be it through diet or even exposure to compounds like BPA, can influence how our genes are expressed, and how our children are programmed to deal with a similar type of environment.  The more we learn about epigenetics, hopefully the more we will learn about preventing non-communicable disease in humans.  Epigenetics is inextricably linked to public health, and the best way to address the effects of obesity on public health is to focus on the upstream factors that influence it.

Disclaimer: this is in NO WAY meant to shame pregnant women or influence their behaviour, or promote nosy people telling pregnant women how to behave.  My angle, besides science, is to promote taking action to provide better services and support to pregnant women.