When I was very small I had a beautiful picturebook Rudyard Kipling book of just-so stories. One I particularly remember is the tale of how the Elephant Got Her Trunk. She was staring at her beautiful nose in a pool every day until one day a crocodile swam up underneath her reflection, grabbed her nose, and pulled and pulled and pulled. The little elephant struggled for so long her nose was stretched all the way down to the ground before the crocodile finally released her. And that, children, is how the elephant got her trunk.
It’s silliness of course, we all know that evolution acts upon the populations, in random genetic mutations, and whatever happens to the individual, so long as it doesn’t stop them reproducing, doesn’t matter. All you need is to procreate, after that the genetic material is mixed and the next line of mutations start.
For the most part, these are the rules of evolution. But all rules have exceptions, and sometimes evolution works through a different mechanism, that of epigenetics.
You don’t come to FluffySciences to find out about cell mechanisms and inheritance (if you are coming here for that we need to have a conversation about our relationship) but you do come here for the real-world explanations. Epigenetics results in a kind of Just So story where a stressful event can result in a change that can be passed down to the next generation. And the Just So story we use to illustrate this isn’t so pleasant.
In the Netherlands in 1944 there was a Hongerwinter, when the Nazis cut off food and fuel transports in the river areas. Tens of thousands of people starved to death. Can you imagine the endless hunger, the enemy soldiers in your streets, the cold? At one point the daily calorie allowance was less than 600 calories.
The immediate effects of this horrible famine were obvious. Pregnant women gave birth to very small babies, children lost the ability to digest wheat, and Aubrey Hepburn developed anaemia. But what happened next?
In Painter et al’s 2008 study (which is open access and you can read here) they investigated the results of the Mothers who starved (F0), their sons and daughters who were born during the famine (F1) and their grandchildren (F2). Using a combination of historical health records, interviews and health checks, they investigated whether the ill health of the granddaughters could be attributed to what the mothers experienced.
Between the 07/01/45 and 08/12/45, children in this cohort were being born to mothers who had, during one of the 13 week periods of gestation, an average daily calorie allowance of 1000 calories. To put this in context, the typical pregnant woman needs 2200 calories per day to maintain both her body and her baby’s growth. In the Dutch Cohort study, children which were born between 01/11/43 – 06/01/45 and 09/12/45-28/02/47 were either born before the famine truly began or conceived after the words was over. They act as controls. They are from the same population, similar mothers, similar time period, even similar psychological stressed. They just don’t have that crippling 1000 calorie a day limitation during the important parts of the baby’s gestation.
The researchers monitored the F1 generation (remember that’s sons and daughters) weight, BMI, Socio-Economic-Status and blood tests to look at how they cope with sugar, and their good and bad cholesterol levels. They did all this when the sons and daughters were 58 years old.
Then they asked about the F2 (grandchildren). Were the grandchildren premature, on time or late? What did they weigh at birth? Were they twins? How many kids? What order? How many girls? How many boys? How healthy are the grandchildren?
At this point the researchers know what has caused the ill health that F1 have suffered – it was the famine. The question is, has this ill health, which was entirely due to a short term environmental challenge experienced in utero, been inherited by the grandchildren? The two categories of disease they were most interested in were cardiovascular/metabolic diseases and psychiatric diseases.
They used a variety of mixed models (which allow you to have multiple children of the same parent, which would otherwise be a case of pseudoreplication), and regression models, among some other statistical tests which can cope with non-parametric (i.e. real world) data to investigate these questions.
Their results showed that the F1 generation were smaller at birth and as adults they had higher blood sugar levels two hours after eating than the ones who hadn’t suffered through the famine. So far so expected. The children of F1 women were also born smaller (though weighed the same) if the F1 woman had been in utero during the famine. This is the really interesting thing. The environmental effect was inherited. Also, the F2 children of the F1 generation who had been exposed to famine earlier in their gestation (i.e. when they were forming) were more likely to have poor health due to ‘other’ causes. Finally, and the one I consider to be most interesting, the F2 generation of those who had suffered in the famine were more prone to being fat babies.
The last point interests me the most. I’m working on a project looking at prenatal effects in farm animals and the way we talk about this phenomenon is to say that the offspring ‘samples’ the mother’s environment in early gestation. For example, if the offspring is receiving little food and lots of stress then it should prepare itself to be born into a world where resources are unpredictable and scarce. Whatever cellular changes it switches on to do this make it predisposed to obesity and heart disease in a normal environment, and can be passed on to its own offspring.
If you remember last week I ranted about nature vs nurture, this is why. This significant change in baby fat in the famine group is not genetics – the population is not genetically different. It’s not the environment, because the famine was long over when these kids were in the womb. It’s historical environment and the changes that produced. Remember, never use Nature Vs Nurture kids.
There’s still plenty we don’t know about epigenetics – how many generations can these effects last for? How cumulative can the total effect be? And when it comes to prenatal effects, what is the mechanism by which the offspring samples the mother’s environment? As a relatively new field, it’s sexy and cool and a lot of people are into it. Expect a lot more information about it in the future.