A recent study challenges the established view of gene change

Certain sequences in the genome turn genes on and off. Until now, it was believed that each of these gene switches, or so-called enhancers, had its own place in DNA. Different enhancers are therefore separated from each other, even if they control the same gene and turn it on in different parts of the body. A recent study from the University of Bonn and LMU Munich challenges this idea. The discoveries are also essential because gene switches They are believed to play a key role in evolution. The study was published in the journal Progress of science.

The pattern of plant and animal forms is encoded in their DNA. But only a compact part of the genome – about two percent in mammals – contains genes, the instructions for making proteins. The rest largely controls when and where these genes are lively: how many of their transcripts are produced, and therefore how many proteins are made from these transcripts.

Some of these regulatory sequences, called “amplifiers”, act like dimmers used to modulate the lithe in our living room. Indeed, they specifically raise the expression of a particular gene where and when that gene is required. Genes that control morphology often respond to several independent enhancers, each of which determines gene expression in a different part of the body.

Control amplifiers Drosophila coloration

Until now, it was believed that amplifiers were modular. This term means that each enhancer occupies an isolated stretch of DNA. “However, we have shown that this is not entirely true,” explains Mariam Museridze. She is a PhD student at the Institute of Organic Biology in Bonn in the group of prof. Dr. Nicolas Gompel and the first author of the work. Gompel is also a member of the Transdisciplinary Research Area (TRA) “Life and Health” at the University of Bonn.

Scientists investigated how the so-called gene yellow is regulated in Drosophila Drosophila. This gene causes the insect to produce brownish melanin, a pigment. There are many enhancers that control activity yellow. One of them is responsible, for example, for the pigmentation of the larvae’s teeth, and the other for the formation of a striped pattern on the fly’s abdomen.

“We took a closer look at two of these amplifiers,” says Museridze. The first one controls the formation of colors on the wings, while the second one controls the coloration of the head, body and abdomen. Both are lively at the same time during the fly’s metamorphosis. The team found that the body enhancer is not, as expected, located in a different region of DNA than the wing enhancer. Instead, there are extensive regions of DNA belonging to both gene switches, i.e. affecting the pigmentation of both the wings and the body.

The results suggest that the architecture of regulatory sequences in the genome is much more sophisticated than previously thought. This has far-reaching consequences for the way traits change over the course of evolution. According to current knowledge, amplifiers play a key role in this process.

Amplifiers as an evolutionary playground

This is because many proteins are so essential to the body that a mutation in their gene (i.e., the DNA sequence that contains the instructions for building a protein) would cause grave problems or even certain death. As a result, genes that control body shape, such as the number of wings or legs, rarely change during evolution. The solution to this dilemma are enhancers: in the case of a mutation, the activity of the corresponding gene changes, but only in a specific tissue and at a specific time.

“Therefore, the cost of an enhancer mutation is often lower than the cost of a direct gene mutation,” says Mariam Museridze. This facilitates the emergence of recent features in the process of evolution. It’s like baking a cake: if you mix eggs, flour, milk and sugar, you can get completely different types of cake, depending on the mixing ratio. In this metaphor, enhancers would be responsible for the quantity of ingredients, not the type of ingredients.

A genetic mutation is like accidentally replacing one ingredient with something completely different – for example, using sawdust instead of flour. The result certainly won’t taste very good. On the other hand, a mutation in the enhancer would change the amount of flour. “If enhancers are not as modular as we thought, it means that mutations in them could have much broader effects,” Museridze says. This means that such a mutation could affect the amount of several ingredients at the same time. However, it is also possible for enhancers to retain their independence and continue to control the amount of a single component even though their sequences are interleaved and shared. “We now want to explore these possibilities in more detail,” explains Professor Gompel. “We also want to find out how general our findings are and how they impact our understanding of evolutionary mechanisms.”