Some sequences within the genome have the ability to activate or deactivate genes. Previously, it was believed that each of these gene regulatory elements, known as enhancers, had a distinct location on the DNA. This meant that different enhancers were positioned apart from one another even if they regulated the same gene, influencing it in various parts of the body. However, a new study from the University of Bonn and LMU Munich calls this idea into question. These findings are significant because gene regulators are considered crucial in the process of evolution.
Certain sequences in the genome can turn genes on or off. Until now, it was thought that each of these gene regulators, or enhancers, existed in a specific location on the DNA strand. Hence, various enhancers were believed to be separated from one another, even when they manage the same gene and activate it in different body regions. A new study conducted by the University of Bonn and LMU Munich challenges this traditional viewpoint. The results hold importance as gene regulators are thought to play a vital role in the evolutionary process. This study has been published in the journal Science Advances.
The genetic instructions that determine the forms of plants and animals are encoded in their DNA. However, only a small fraction of the genome—around two percent in mammals—contains genes that give the directives to produce proteins. The remainder primarily regulates when and where these genes are active, influencing the quantity of their transcripts produced and consequently the number of proteins synthesized from these transcripts.
Some of these regulatory sequences, known as ‘enhancers’, function similarly to dimmer switches that adjust the light in our homes. They specifically enhance the expression of certain genes when and where they are needed. Genes responsible for physical traits typically respond to multiple independent enhancers, each of which determines how the gene is expressed in various body parts.
Enhancers influencing Drosophila coloration
Until now, it was assumed that enhancers were modular, meaning that each enhancer existed in an isolated section of DNA. “However, we have demonstrated that this notion isn’t entirely accurate,” asserts Mariam Museridze, a PhD candidate at the Bonn Institute of Organismic Biology in Prof. Dr. Nicolas Gompel’s lab and the lead author of the study. Gompel is also associated with the Transdisciplinary Research Area (TRA) ‘Life & Health’ at the University of Bonn.
The researchers investigated the regulation of a gene called yellow in the fruit fly Drosophila. This gene prompts the insect to generate the brownish pigment melanin. Numerous enhancers oversee the expression of yellow. One such enhancer is responsible for the pigmentation of the maggots’ teeth, while another controls the striped pattern that appears on the fly’s abdomen.
“We closely examined two of these enhancers,” explains Museridze. The first enhancer governs the color patterns on the wings, while the second regulates the coloration of the head, thorax, and abdomen. Interestingly, both enhancers are active simultaneously during the fly’s metamorphosis. The research team found that the body enhancer is not situated in a different region of DNA as expected; rather, there are substantial DNA segments that are shared by both gene regulators, meaning they both influence the pigmentation of the wing and the body.
This suggests that the arrangement of regulatory sequences within the genome is far more intricate than previously believed. This realization has significant consequences for understanding how traits evolve over time, as current scientific knowledge indicates that enhancers are integral to this process.
Enhancers as a playing field for evolution
This is crucial because certain proteins are so essential for survival that mutations in their corresponding genes (the segments of DNA that contain instructions for protein synthesis) can lead to severe issues or even death. Consequently, genes that dictate an organism’s body structure, like the number of wings or legs, tend to remain stable throughout evolutionary changes. Enhancers offer a potential pathway for variability: mutations in these regions may alter the activity of the associated gene, but only in specific tissues and at certain times.
“Thus, the repercussions of mutating an enhancer are often less severe than those of directly mutating the gene,” explains Mariam Museridze. This phenomenon facilitates the emergence of new traits during evolution. It’s akin to baking a cake: by combining eggs, flour, milk, and sugar in varying ratios, one can create different types of batter. In this analogy, enhancers control the quantity of the ingredients rather than the types.
A genetic mutation resembles mistakenly substituting one ingredient for an entirely different one—like swapping flour for sawdust. The outcome is unlikely to be favorable. Conversely, a mutation in an enhancer would merely adjust the quantity of flour. “If enhancers are not as modular as previously thought, this suggests that mutations in them could have far more extensive effects,” notes Museridze. This could mean that such mutations might influence several ingredients simultaneously. However, it’s also possible for enhancers to maintain their distinct functions and continue regulating a single ingredient, despite their intertwined sequences. “We aim to explore these possibilities further,” states Professor Gompel. “We also want to determine how widely applicable our findings are and how they may reshape our understanding of evolutionary mechanisms.”
Participating Institutions and funding:
Prof. Gompel and his research team commenced their study at LMU Munich and concluded it at the University of Bonn. The University of California at Davis, USA, also contributed to this research. The study was financially supported by the German Research Foundation (DFG) and LMU Munich.
