People share some genes with trees

Epigenetics

More than the sum of its genes

The term "epigenetics" is made up of the words genetics and epigenesis, i.e. the development of a living being. Epigenetics is considered to be the link between environmental influences and genes: it helps determine under which circumstances which gene is switched on and when it becomes silent again. Experts speak of gene regulation here.

After deciphering the first human genome, one now had a text with around three billion letter pairs made up of the four letters A, C, G and T. But the secrets of the human blueprint were not really deciphered. It is now clear: Genes not only control, they are also controlled.

The human genome, i.e. all around 25,000 genes, does not yet explain why one person gets Alzheimer's disease and the other has difficulty coping with stress, why two people have the same cancer gene but only one of them also gets cancer. This can be explained, however, with epigenetics, an emerging field of research in biology.

Same genome, different epigenomes

"Humans have more than 200 cell types, and almost every cell has the same DNA sequence, but not all genes are active in every cell," says Thomas Jenuwein from the Max Planck Institute for Immunobiology and Epigenetics. "The primary information that defines a person is of course the gene sequence, otherwise identical twins would not be genetically identical and so outwardly similar".

But epigenetic changes ensure that only one twin is more susceptible to, for example, diabetes. When Spanish researchers examined genetically identical pairs of twins between the ages of three and 74, it became clear that the youngest twins hardly differed in their epigenetic code - the oldest twins, however, immensely.

In the course of life, twins go through different things, develop different habits or find themselves in different life circumstances - and so their epigenetic codes sometimes develop in different directions.

"Second code" made of mini-molecules

But what does such an epigenetic code actually look like? The best-known way in which epigenetics works is methylation. Small molecules - so-called methyl groups made up of one carbon atom and three hydrogen atoms - dock onto the DNA strand and prevent the subsequent gene sequence from being read and translated into a protein. This is how the gene is turned off.

The so-called histone acetylation also plays an important role in epigenetic marking: so that the two-meter-long DNA strand of a cell also fits into the tiny cell nucleus, it must be packed very tightly. The strand winds around up to hundreds of thousands of pearls, the histone complexes.

In order to activate the genes located there, the genetic material must first be unpacked again. Small molecules help here, the acetyl groups, which loosen the DNA strand and make the genes readable at this point.

On the map of the human genome, you can then mark the places with the special molecules and thus receive the epigenome as a "second code" in addition to the genetic code.

However, there is not just a second code: a person has countless epigenomes. After all, each cell type contains the same gene sequence, but different markings.

Green tea and royal jelly turn on good genes

Epigenetics opens up many a black box: It has long been known that green tea is so healthy that it improves cancer statistics in Japan. But why this is so could only be clarified with epigenetics. When the unfermented tea leaves are brewed, a substance known as epigallocatechin-3-gallate (EGCG) is released.

This substance reactivates a gene that provides the blueprint for a cancer-fighting substance. In older people in particular, this gene is often methylated and therefore mute - the anti-cancer effect of this one gene would be gone. The green tea acts like a peeling for the gene sequence.

In the case of bees, too, it becomes clear how much food alone can have an epigenetic effect: anyone who receives a honey-pollen pulp becomes a sterile worker bee, and anyone who is allowed to snack on royal jelly becomes a queen.

Scientists have now found out why this is so: The honey-pollen pulp ensures that genes for bee development are extraordinarily methylated and thus muted. Conversely, royal jelly contains up to five percent of a fatty acid that can epigenetically reactivate muted genes.

"Trauma scarring the genome"

Human relationships also have a lasting influence on the epigenome and thus on life and health: an infant, for example, who receives too little love and security, apparently not only has attachment problems, but also has biologically verifiable disorders in the stress hormone system.

"Traumas not only cause scars in the soul, but also scars in the genome," says depression researcher Florian Holsboer, illustrating the epigenetic markings. If these scars are also in the genome of the germ cells, then they are even passed on, as epigeneticists have found out.

Epigenetic markings can be inherited

An example of epigenetic memory is that of the pregnant Dutch women from the hunger winter of 1944/45. That the women gave birth to underweight babies seems plausible.

But then it turned out that the offspring had an above-average rate of depression, obesity or schizophrenia. The children developed age-related diseases such as heart problems and diabetes at an astonishingly early age.

Another investigation showed that the sons of the "hungry winter mothers" had predominantly overweight offspring. The experience of these mothers and the resulting endeavor to prevent a famine by building up fat reserves thus apparently had an effect on the next generation but one - even though the grandchildren at a time with food in abundance and with fewer needs had been conceived.

The genetic material of the grandchildren apparently also contained information about the living conditions of the grandparents.

Against this thesis, however, speaks that the offspring of the daughters of the "hungry winter mothers" were hardly overweight. Scientists such as Steven Henikoff, who researches gene regulation at the Fred Hutchinson Cancer Research Center in Seattle, assume that the overweight offspring of these mothers' sons can be traced back to poor eating habits of the parents, which also affected the children.

Discussion about theories of evolution

This has sparked a controversial discussion among scientists. Because it's no longer just about methyl groups, genes and databases, but also about the theory of evolution.

"The epigenetic memory shows that Lamarck has to be rehabilitated," said some. The French biologist Jean-Baptiste Lamarck was the adversary of Charles Darwin and developed one of the first theories of evolution in the 19th century.

According to this, giraffes, for example, craned their necks the higher the tasty leaves hung on the trees. This elongated throat would then be passed on to the offspring.

Properties that only develop in the course of a lifetime are inherited: that was Lamarck's thesis and this is what happens in epigenetics when gene switches are turned on in sperm or egg cells and these switches are passed on to the offspring.

In contrast, the others say that epigenetics is part of Darwin's adaptation mechanism. Because according to the postulate, it is not the strongest who survive, but the individual who is best adapted to his environment and living situation. Epigeneticist Thomas Jenuwein explains it this way:

"Epigenetics represents soft changes, changes that make up the ability to adapt in a life, but which can definitely be reversed. Genetics, on the other hand, makes for hard changes, because DNA mutations are not reversible. This means that these mutations drive evolution in front. "

Epigenetic inheritance in humans also appears to be rather unlikely, since there is a strict separation between body cells and germ cells in all mammals. Body cells react to environmental influences, but cannot pass this information on to offspring.

Only the germ cells can do that. With them, however, almost all epigenetic markers are carefully removed in two "cleansing waves". In contrast, plants know neither this strict separation nor the two waves of cleansing. This is why epigenetic inheritance is much more common among them.

New findings for medicine?

Maybe Lamarck's theory of evolution is just part of Darwin's theory? Scientists will probably not run out of theses for discussions and approaches for research in the coming years.

Where else can we see that epigenetic changes are inherited? How exactly do the epigenetic mechanisms work in detail? Which genes are switched on by which foods and lifestyles and which are switched off? And how can this be used for the treatment of diseases?

However, it is unclear whether they will find valid answers to these questions. Some scientists do not expect any important new findings for medicine from epigenetic research.

They justify this with the fact that most studies that want to prove that the causes of diseases lie in the epigenome suffer from problems in design and implementation, so that their interpretability is severely impaired. In their view, it is difficult to determine unequivocally whether the state of an epigenetic regulation being investigated is actually a possible cause or at least a consequence of a disease.

In addition, evidence of epigenetic influences in humans can hardly be carried out. Because while animals and plants can be crossed and manipulated in a controlled manner, this is impossible with humans. And results from animal experiments cannot easily be transferred to humans.

In contrast, other scientists attach great importance to epigenetics. They hope that this will provide a better understanding of diseases and their treatment and assume that epigenetics will open up new avenues in medical research.

So it remains to be seen and exciting whether and which surprises epigenetics has in store for the next few years.