Tuesday, 16 October 2012

Identically Differernt

Tim Spector is Professor of Genetic Epidemiology at King's College London and in 'Identically Different' he teases apart how identical genes do not lead to identical outcomes.  We are of course talking about epigenetics.

Much of Spector's work involves looking at the genetics of twins.  Twin can be identical (concordant), or non-identical (discordant).  Identical twins share all their genes while non-identical twins share, on average, about half. Factoring in the likely similar upbringing of twins the heritability of a particular trait or condition can be calculated by analysing that trait of condition amongst the populations of discordant and concordant twins.  The two main epigenetic principles are DNA methylation and Histone modification.

Methylation involves methyl marks (which Spector describes as looking like an 'olive on a cocktail stick') sticking to DNA bases (the 'rungs' you see on a double helix), which repress gene activity by stopping the gene producing a protein.  Methylation turns a gene 'off' whilst unmethylated DNA bases are expressed (more protein is produced).  Unlike a mutation, methylation is reversible, although the effects can last for generations.

Histone modification acts more like a volume control.  The histones have protein 'tails' to which molecules can attach, altering the activity of DNA and exposing them to other changes.

Back to the book.  Spector digs out an interesting example of how stress can precipitate epigenetic change.  Parent chickens were taken from the same genetic stock.  One half were housed in an environment of regular 12 hour cycles of light and dark, whilst the second group were exposed to a unpredictable light cycles.  In both cases food was only available during daylight hours,

  • "The researchers then looked at the eating patterns of the offspring of both groups when they were now all raised uniformly in the comfortable regular daylight and eating lifestyle.  Those parents raised in the Guantanamo Bay-style who had never met either of their parents had a more efficient and aggressive  eating behaviour than their genetically identical but parentally privileged coop mates, who were more relaxed and preferred to look around for more tasty worms who often got away. The efficient policy worked and the Guantanamo chickens got fatter.  The researchers  saw epigenetic changes in the offspring and suggested these had affected immune and hormonal genes such as oestrogen.  This suggested how epigenetics could provide survival  advantages.  Environmental stresses could prime future generations to be able to cope better in the same situations - a brilliantly effective form of short-term evolution."
Touching on some of the topics covered in Rainy Brain Sunny Brain, Spector looks at research on optimism,
"Most studies show that there is generally a slight (20 per cent), advantage to being optimistic in life when dealing with the after-effects of major life events or illnesses, such as bereavement, cancer or heart attacks.  Pessimism has, as expected, the opposite effect.  But sometimes you can be too optimistic.  Extreme optimists who guess they would live 20 years more than the national average were compared with moderate optimists (the majority) who overestimated by a few years and pessimists who thought they would die early.  The study found that the moderate optimists worked hard, saved well and smoked less, compared with the extreme overconfident optimists, who worked less, saved less and smoked more."

By way of example, Spector draws on the experience of POW James Bond Stockdale who survived his horrendous imprisonment where his fellow captives perished, by recourse to measure optimism.  Bond later said of his experience,
  • "This is a very important lesson.  You must never confuse faith that you will prevail in the end - which you can never afford to lose - with the discipline to confront the most brutal facts of your current reality whatever they might be."
Nowhere is the powerful myth of 'favourable genetics' more prevalent than in the world of sport.  Perhaps the most studied are the Kenyans - 90% of whose elite runners come from a small are of the Rift Valley in Africa.  They live at altitude and due to poverty cover large distances on foot each day, for example, travelling to and from school.  So we seem to have some strong environmental factors that would seem to predicate excellent physical endurance.  But the world record holder in the Marathon, Haile Gabreselassie, is actually Ethiopian,
  • "...he too ran to school from the age of five, despite his skin colour his genes, like most of his countrymen's, are much more similar to Europeans' than to kenyans'.  While we are readily biased by the colour of someones skin when predicting their physical or intellectual abilities, surprisingly skin colour is controlled by just a handful of genes, and is a poor guide to the other 25,000 underneath.  Indeed there is more genetic diversity in one small are of Africa than there is in the whole of Europe."
Talking of sport, exercise would seem to profoundly effect epignetics - not least from a study which showed athletes possessed gene variants that inhibited methylation - and adds to a body of evidence suggesting couch potatoes exhibit greater methylation.  Lower rates of methylation 'stimulate muscle cells and muscle growth more than average in response to exercise'. Various experiments on rats sought to unpick this relationship.  Dividing the rats in to one of two groups, one group was encouraged to exercise on a treadmill and the other group were encouraged to rest.  After a four week program the gym-rat rats were found to perform much better in 'tests of physique and response to stress',
  • "This wasn't a particular shock, but what happened in the brain was.  The genes in a key part of their brain, the dentate gyrus, had been modified epigenetically.  This is a part of the brain in the cerebellum that controls muscle movement.  There was a clear methylation difference between the rat groups."
A great read.

2 comments:

Chuck said...

interesting post. regarding the influence of exercise and sport, i did a post on that a while back. it has a tremendous influence.
http://escapetheherdblog.blogspot.com/2010/12/stop-blaming-your-parents.html

Asclepius said...

Cheers Chuck. I will check it out.