Biophysical constraints on evolvability and robustness uncovered - Study published in Nature Ecology and Evolution
It is often thought that DNA, together with the genes encoded in it, is the essence of life. But equally important is coordinating when genes are turned on and off. In fact, it is this process, called regulation of gene expression, that defines life by allowing organisms to react to their surroundings rather than being static automatons.
As even the smallest organisms like bacteria have many genes, coordinating their expression is done by a dedicated set of proteins, which bind specific sites in the DNA (called ‘promoters’) in order to turn genes on or off. Each such pairing between a protein and its associated promoter constitutes one of myriad connections in the organismal gene regulatory network.
Gene regulatory networks are intricately tuned, so how can they evolve and change? In a study published today in Nature Ecology and Evolution, a team of researchers at the Institute of Science and Technology Austria (IST Austria), including co-first authors Claudia Igler (PhD student in Calin Guet’s group) and Mato Lagator (Postdoc in the Guet group), as well as Calin Guet, Gašper Tkačik and Jonathan Bollback (University of Liverpool), describes how individual regulatory connections can change over time.
Usually, gene regulatory networks are studied at the global level, with researchers seeking to understand how the properties of the network as a whole determine its evolution. Igler et al., however, decided to study network evolution from the local perspective in order to understand how connections in the network change. To do so, they used two DNA-binding proteins and their associated promoters. These proteins are called ‘repressors’, as their binding to DNA inhibits gene expression.
The researchers then introduced mutations into the promoters and observed how these changes affected the binding of repressors. Repressors can react to changes in two ways, Igler says: “A repressor can be robust, meaning that mutations do not affect it much since it maintains binding to a promoter despite the mutations. Alternatively, a repressor can be evolvable, which means that it readily responds to mutations by acquiring binding to new promoters. These two responses to mutations seem to be, by definition, mutually exclusive – a protein that is more robust to mutations ought to respond to mutations less, and should hence be less evolvable!”
But, as is often the case, biology is full of surprises. Comparing between the two studied repressors, the researchers found that the more robust repressor acquired binding to new promoters more readily.
By developing a biophysical model based on the thermodynamics of protein-DNA binding, the researchers were not only able to explain their surprising observations, but could generalize their findings, as Igler describes:
“How repressors react to mutations in their binding sites indicates how they can function within the regulatory network. One group of repressors, the local ones, are very specific – they bind only to a handful of promoters and do not acquire new binding easily. Another group of repressors, the global ones, is promiscuous and keeps on binding to their promoter even when it is heavily mutated, while also easily starting to bind new sites.”
Claudia Igler, one of the paper’s co-first authors, is a PhD student in the group of Calin Guet. IST Austria’s interdisciplinary graduate school offers fully-funded PhD positions in the natural and mathematical sciences. For Igler, the requirement to work with different groups in the initial rotation year was the graduate school’s strongest point:
“I come from a theoretical background in mathematical and biomedical engineering. However, I had always wanted to try working in a lab. IST Austria’s graduate school was ideal as the rotations allowed me to see whether experimental work fitted me. Although I had initially thought I’d work in neuroscience, I joined Calin Guet for my first rotation and liked it so much that I decided to stay here.” Applications for the next year of study at the IST Austria graduate school start in mid-October: http://phd.ist.ac.at
Bernhard Wenzl | idw - Informationsdienst Wissenschaft
Blocking the iron transport could stop tuberculosis
02.04.2020 | University of Zurich
Discovery of life in solid rock deep beneath sea may inspire new search for life on Mars
02.04.2020 | University of Tokyo
90 million-year-old forest soil provides unexpected evidence for exceptionally warm climate near the South Pole in the Cretaceous
An international team of researchers led by geoscientists from the Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research (AWI) have now...
The bacteria that cause tuberculosis need iron to survive. Researchers at the University of Zurich have now solved the first detailed structure of the transport protein responsible for the iron supply. When the iron transport into the bacteria is inhibited, the pathogen can no longer grow. This opens novel ways to develop targeted tuberculosis drugs.
One of the most devastating pathogens that lives inside human cells is Mycobacterium tuberculosis, the bacillus that causes tuberculosis. According to the...
An international team with the participation of Prof. Dr. Michael Kues from the Cluster of Excellence PhoenixD at Leibniz University Hannover has developed a new method for generating quantum-entangled photons in a spectral range of light that was previously inaccessible. The discovery can make the encryption of satellite-based communications much more secure in the future.
A 15-member research team from the UK, Germany and Japan has developed a new method for generating and detecting quantum-entangled photons at a wavelength of...
Together with their colleagues from the University of Würzburg, physicists from the group of Professor Alexander Szameit at the University of Rostock have devised a “funnel” for photons. Their discovery was recently published in the renowned journal Science and holds great promise for novel ultra-sensitive detectors as well as innovative applications in telecommunications and information processing.
The quantum-optical properties of light and its interaction with matter has fascinated the Rostock professor Alexander Szameit since College.
Researchers at the University of Zurich show that different stem cell populations are innervated in distinct ways. Innervation may therefore be crucial for proper tissue regeneration. They also demonstrate that cancer stem cells likewise establish contacts with nerves. Targeting tumour innervation could thus lead to new cancer therapies.
Stem cells can generate a variety of specific tissues and are increasingly used for clinical applications such as the replacement of bone or cartilage....
02.04.2020 | Event News
26.03.2020 | Event News
23.03.2020 | Event News
02.04.2020 | Physics and Astronomy
02.04.2020 | Information Technology
02.04.2020 | Health and Medicine