By Sandra Hake and Philipp Korber of Ludwig-Maximilians-Universität Munich
Recently researchers have made the astonishing finding that our lifestyles seem to have lasting effects on our offspring as well. What is passed on from our ancestors?
What are the biological gifts that our bodies have received from our parents? The textbook answer is “genes encoded in DNA”. However, “You can inherit something beyond the DNA sequence. That’s where the real excitement in genetics is now”, said J. Watson in a 2003 Scientific American interview. Epigenetics, literally “on top of” genetics, is the study of how information can be securely and stably inherited beyond the DNA sequence. While such mechanisms really exist, it remains unclear how important and widespread they are. With lots of hype and hope it is debated if information gathered during one’s life may be biologically heritable.
In the classical view, cells contain all information to build new cells, tissues, organs and whole organisms in the form of DNA. Indeed, explaining Mendelian genetics through the molecular biology of DNA is a cornerstone of biology. Nonetheless, there were always perplexing observations of non-Mendelian inheritance, traits not linked to DNA-encoded information, that have puzzled geneticists. For example, identical genes had different effects if inherited from father or mother (“parental imprinting”). Or different seed colours in maize could be inherited without genetic mutations (“paramutation”). For a long time such “epigenetic” phenomena had an esoteric smack to them. There just was no scientific explanation.
But there is more. Our own bodies are full of epigenetic phenomena. Since all cells stem from a single fertilized egg cell, they all contain the same DNA. Nonetheless, liver cells differ from skin or nerve cells. Upon cell division they give rise to more liver cells but not to other cell types. That is epigenetics: heritability of different properties (“phenotype”) without changing the genetic information (“genotype”).
Lifetime-lasting tissue specificity found in cells originates from activating only those genes necessary to “program” a particular cell type and silencing the rest. For example, liver cells always give rise to more liver cells but never to kidney cells. So the key to epigenetics is the precise and heritable regulation of gene expression.
How does this work? Cellular DNA is not “naked” but packaged with proteins into a complex structure called chromatin. It looks like a pearl necklace, with the DNA being the string and the protein complexes being the pearls. Chromatin is highly variable: the pearls change their position and composition (“variants” and “modification tags”), and the DNA string becomes more stretched out or curled up, depending on how the pearls interact with each other.
For a long time different forms of chromatin were mainly viewed as a means to package the long DNA string into the cell nucleus. However, recently it has become clear that these structural changes “on top of” DNA are an important layer of information that may be inherited from cell to cell. They are like traffic lights, switchable “stop” and “go” signs that the cell uses to interpret whether or not to translate certain genes into cellular functions.
So chromatin, together with small modifications of the DNA itself (“methylation”), is now recognized as the molecular vehicle for epigenetics.
Our research groups have studied the variations in chromatin building blocks as well as the mechanisms of their positioning. We and others find that there is a whole nuclear system to be unravelled, a system dedicated to regulating genes by structuring DNA into chromatin.
This concept shows the plausibility of inheritance from cell to cell. Is it then also true for inheritance across generations, from organism to organism? Do our parents pass on just DNA and genes, or do we also inherit epigenetic structures for gene regulation? There is the rub. Besides a few cases of DNA methylation, it is unclear if chromatin information is passed on from parents to children. Second, epigenetic structures—much more than DNA—are influenced by the environment and by “experiences” our cells make.
Take, for example, the case of monozygotic twins. Being always genetically identical, twin siblings are exposed to different experiences during life and become different from each other. With age, each twin acquires different chromatin structures in certain cells.
Apparently, the environment affects the epigenetic information. Food, for example, very likely sends signals to the epigenetic building blocks, affects chromatin patterns and consequently influences gene regulation and phenotypic outcomes.
Are the only cells that are passed on to the next generation—egg and sperm cells—subject to such effects, too? Only then would chromatin changes be heritable and constitute true epigenetic marks. Are we therefore not only shaped by our ancestors’ genes but also by the food they ate, by their lifestyle and experiences?
So is this science or science fiction? Recent animal and human studies indeed suggest that environmental effects on egg and sperm cells cause lasting epigenetic changes in the offspring. For example, hunger periods in critical life phases of grandparents seem to correlate with an increased risk for diabetes in their children and grandchildren.
Another study reported adverse effects through four generations of rat offspring that were exposed to noxious chemicals. Epigenetics is not biological science fiction anymore.
However, despite excitement and increased efforts, there are still no clear-cut examples to show whether or not the body uses epigenetic mechanisms to pass on “experience” and pervade and shape biology through generations in a Lamarckian way, or if such mechanisms are at most rare episodes. This will decide whether epigenetics will change the worldview mainly for biologists or for society at large. In the future, your grandchildren might thank you not only for birthday presents but also for the healthy lifestyle you lived before their parent was born.
Sandra Hake and Philipp Korber