Diet and DNA

How a mother's diet during early development can affect offspring decades later
February 6, 2009 Scientists know that human development is a combination of genes and environment. Some traits like blood type are completely determined by genes. Other traits such as finger length are due to both genes and environment. In this last case, hormones in utero affect fingers without changing any genes. But sometimes environment can actually affect genes in a specific way. It's something that scientists have shown in animals before (see below), but a recent study is the first to show that it's true in humans too! What they found was that a mother's diet can affect one of her children's genes -- the IGF2 gene. This change affects how this gene works even when the children have grown up.
Famine Affects the IGF2 Gene

What this mom eats
can affect herchild's DNA.
Scientists have wanted to investigate the effects of mom's diet on her children's DNA for a long time. But it obviously wouldn't be right to do tests with pregnant women. So scientists needed another way to test their ideas. What they used were people who were born during a famine. Famine means time where people didn't have enough food. In 1944-1945 there was a famine in the Netherlands. Scientists decided to look at the DNA of people who were conceived and/or born during the famine. They compared these people's DNA to their brothers and sisters born during normal times. In this study scientists decided to look at a gene in these people's DNA called IGF2. This gene is involved in human growth and development. So if the famine affected this gene, then it could have long-term effects on the health of the baby as it grew into an adult. The scientists studied the following two groups of people 60 years after they were born:
  1. People whose moms were exposed to the famine during the very early part of pregnancy.
  2. People whose moms were exposed to the famine during the late part of pregnancy.
The scientists found the IGF2 gene of people whose moms were exposed to famine during early pregnancy were different than their siblings. But those exposed to famine during late pregnancy had no changes to their DNA. This means that mom's diet while pregnant can affect her children's DNA. But only if the famine is during the early days of pregnancy. And those DNA changes can stay around for at least 60 years. Genes and DNA structure So what exactly are these changes? And why did it only happen in those whose mothers were exposed to famine early in pregnancy? To answer these questions we first have to understand the basics of genes and DNA structure. A gene is a piece of DNA. DNA is made up of four bases called A, T, G and C. Cells read this DNA and, following its instructions, make a protein. Proteins are molecules that are involved in almost everything a cell does. The IGF2 gene has the instructions for the Insulin-like Growth Factor 2 protein. This protein promotes growth and division of cells. And it is most active during fetal development. The changes the scientists studied in the IGF2 gene are not in its bases. Instead they looked at DNA changes that affect how often a gene gets read. And so, how much protein gets made. A gene doesn't only have the instructions for making a certain protein. It also includes information about when and how much protein to make. This is because every cell doesn't make the same amount of every protein. That's why our cells are so different even though they have the same DNA. Cells control which and how much protein gets made by turning genes on and off. The human body has over 6 feet of DNA packed into each cell. So in order for genes to get turned on the compact DNA needs to be loosened up so the cell can read the DNA sequence. DNA Methylation Turns Genes On or Off One way in which cells can loosen or tighten DNA to turn genes on or off is by something called epigenetics. It sounds complicated but breaking the word apart shows it's actually very simple.

DNA methylation turns
genes on and off.
"Epi" comes from Greek and means "on" or "over". And genetics refers to a gene. So "epigenetic" literally means "on a gene. Methylation is an epigenetic way to affect a gene (see picture at right). Methylation refers to a methyl group placed on or taken off a gene. A methyl is a very small chemical group made up of one carbon atom and three hydrogen atoms. Usually more methylation means a gene is turned off and less methylation means a gene is turned on. Methylation is one example of how genes can be directly affected by the environment. The environment can actually change how many methyl groups are placed on the DNA. This then leads to genes being turned on or off. For example, previous studies with animals have shown that a mother's diet during pregnancy can affect how methylated her children's DNA is. One study altered the diet of pregnant mice. Depending on what the mom ate the baby pups came out either yellow or brown. This was because of differences in methylation on certain genes. What's more interesting is that the yellow pups grew up to have yellow babies. And the brown mice grew up to have brown babies. That means the differences in DNA methylation stayed with the pups their whole lives. And even into their babies lives! So the scientists in this famine study set out to find out if something similar was happening in people. They indeed found that famine affected the methylation of the IGF2 gene. But only if the famine happened early in pregnancy.

More Information

Genes are written
in the DNA letters
A, G, T, and C.
Famine in Early Pregnancy Reduces IGF2 Methylation
The scientists found the IGF2 gene of people whose moms were exposed to famine during early pregnancy had less methylation. That means the gene was probably turned on more than their siblings' gene. But the scientists did not see the same thing with people whose moms were exposed to famine in late pregnancy. Those babies weighed less when they were born because the moms didn't have enough food. But the methylation on their IGF2 gene was no different from their brothers' and sisters'. What this means is that there's a critical time for methylation. This actually supports something scientists have known a long time about methylation. Most of the methyl groups are removed from the DNA of early embryos when they are made up of only about 8 cells. Then new methyl groups are placed on the DNA. It's the embryo's way of starting from a clean slate. So a mother's diet only during early pregnancy affects the way in which her embryo's DNA is methylated. And this methylation can last a lifetime. But why does it matter if the DNA is methylated after 60 years? Does this have any effects on child and adult development? The scientists in this study didn't look at anything else other than the DNA methylation. They didn't study the health of these people. But other studies in animals have shown that changes in DNA methylation can be a very permanent and serious thing. Famine and Later Health

Sibling mice look different
because of mom's diet.
Remember those yellow and brown mice? Turns out that the color of their fur wasn't the only thing that was affected from their mother's diet. The mice whose moms didn't have enough nutrition were yellow. These mice also had higher rates of obesity and diabetes. And just like the yellow color of their fur this risk was passed down to their pups too. Other studies in animals have also shown that famine and decreased methylation can have long-term health effects. One study showed that sheep without enough vitamins gave birth to babies that had less methylation on their DNA. Even though these babies were normal at birth they had many health problems as they got older. This included being fatter, decreased ability to fight infections and increased blood pressure. And these connections between famine and health are seen in humans too. Some scientists have shown that famine during the early parts of pregnancy can lead to schizophrenia and heart disease in humans. They haven't done any studies to prove this is because of DNA methylation. But famine does change DNA methylation so changes in methylation could be related to these problems. Its clear that what a mom eats during pregnancy is important. Especially during the very early parts of pregnancy. It can affect the DNA and health of her baby even into adulthood. So that old saying "you are what you eat" should really be "you are what your MOM eats!" Jackie Benjamin