Epigenetics: DNA Isn’t Everything

A certain laboratory strain of the fruit fly Drosophila melanogaster has white eyes. If the surrounding temperature of the embryos, which are normally nurtured at 25 degrees Celsius, is briefly raised to 37 degrees Celsius, the flies later hatch with red eyes. If these flies are again crossed, the following generations are partly red-eyed – without further temperature treatment – even though only white-eyed flies are expected according to the rules of genetics.

Environment affects inheritance

Researchers in a group led by Renato Paro, professor for Biosystems at the Department of Biosystems Science and Engineering (D-BSSE), crossed the flies for six generations. In this experiment, they were able to prove that the temperature treatment changes the eye colour of this specific strain of fly, and that the treated individual flies pass on the change to their offspring over several generations. However, the DNA sequence for the gene responsible for eye colour was proven to remain the same for white-eyed parents and red-eyed offspring.

The concept of epigenetics offers an explanation for this result. Epigenetics examines the inheritance of characteristics that are not set out in the DNA sequence. For Paro, epigenetic mechanisms form an additional, paramount level of information to the genetic information of DNA.

Such phenomena could only be examined in a descriptive manner in the past. Today, it has been scientifically proven, which molecular structures are involved: important factors are the histones, a kind of packaging material for the DNA, in order to store DNA in an ordered and space-saving way. It is now clear that these proteins have additional roles to play. Depending on the chemical group they carry, if they are acetylated or methylated, they permanently activate or deactivate genes. New methods now allow researchers to sometimes directly show which genes have been activated or deactivated by the histones.

Cells have a memory

Epigenetic marks, such as the modifications of the histones, are also important for the specialisation of the body’s cells. They are preserved during cell division and are passed on to the daughter cells. If skin cells divide, more skin cells are created; liver cells form liver cells. In both cell types, all genes are deactivated except the ones needed by a skin or liver cell to be a skin or liver cell, and to function appropriately. The genetic information of the DNA is passed on along with the relevant epigenetic information for the respective cell type.

Paro’s group is researching this cell memory. It is still unclear how the epigenetic markers are passed on to the daughter cells. During cell division, the DNA is doubled, which requires the histones – as the current picture suggests – to break apart. The question is therefore how cellular memory encoded by epigenetic mechanisms survives cell division.

Emerging area of research

A similar question remains for the inheritance of the epigenetic characteristics from parents to offspring. They now know that when the gametes are formed, certain epigenetic markers remain and are passed on to the offspring. The questions, which are currently being researched, are how much and which part of the epigenetic information is preserved and subsequently inherited.

The research is also looking at the influence of various substances from the environment on the epigenetic constitution of organisms, including humans. Diet and epigenetics appear to be closely linked. The most well known example is that of the Agouti mice: they are yellow, fat and are prone to diabetes and cancer. If Agouti females are fed with a cocktail of vitamin B12, folic acid and cholin, directly prior to and during pregnancy, they give birth to mainly brown, slim and healthy offspring. They in turn mainly have offspring similar to themselves.

Contradiction to Darwin?

Environmental factors, which change the characteristics of an individual and are then passed on to its offspring, do not really fit into Darwin’s theory of evolution. According to his theory, evolution is the result of the population and not the single individual. “Passing on the gained characteristics fits more to Lamarck’s theory of evolution”, says Paro.

However, he still does not believe Darwin’s theory of evolution is put into question by the evidence of epigenetics research. “Darwin was 100 percent right”, Paro emphasises. For him, epigenetics complement Darwin’s theory. In his view, new characteristics are generated and passed on via epigenetics, subject to the same mechanisms of evolution as those with a purely genetic origin.