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
Special Antibodies Could Lead to HIV Vaccine
10.09.2018 | Universität Zürich
Kidnapping in the Antarctic animal world?
10.09.2018 | Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung
Graphene is considered a promising candidate for the nanoelectronics of the future. In theory, it should allow clock rates up to a thousand times faster than today’s silicon-based electronics. Scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) and the University of Duisburg-Essen (UDE), in cooperation with the Max Planck Institute for Polymer Research (MPI-P), have now shown for the first time that graphene can actually convert electronic signals with frequencies in the gigahertz range – which correspond to today’s clock rates – extremely efficiently into signals with several times higher frequency. The researchers present their results in the scientific journal “Nature”.
Graphene – an ultrathin material consisting of a single layer of interlinked carbon atoms – is considered a promising candidate for the nanoelectronics of the...
Organic light-emitting diodes (OLED) are mainly known from televisions and smartphone displays. They can be used as lighting objects in car tail lights or lights. The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP as a partner for customer-specific OLED development and production is now presenting OLED elements that can be integrated into textiles at the Electronics System Integration Technology Conference ESTC 2018 from September 18 - 21, 2018 in Dresden at booth no. 29.
The versatile OLEDs can not only light in color, they can also be designed in any shape and even transparent or dimmable. Applied on wafer-thin foils, they are...
Scientists at the Max Planck Institute for Intelligent Systems in Stuttgart invented a new and cost-effective method for making X-ray lenses with nanometer-sized features and excellent focusing capabilities. By using an advanced 3D printing technique, a single lens can be manufactured under a minute from polymeric materials with extremely favorable X-ray optical properties, hence the costs of prototyping and manufacturing are strongly reduced. High-throughput and high-yield manufacturing processes of such lenses are sought after world-wide, which is why the scientists have filed a patent for their invention.
X-ray microscopes are fascinating imaging tools. They uniquely combine nanometer-size resolution with a large penetration depth: X-ray microscopy or XRM is the...
Physicists from Konstanz produced extremely short and specifically-shaped electron pulses for materials studies in the femtosecond and attosecond range in collaboration with Munich-based institutes
Our world is basically made up of atoms and electrons. They are very small and move around very rapidly in case of processes or reactions. Although seeing...
Hannover Messe is expanding to the USA – and Fraunhofer IPK is joining in with a trendsetting exhibit. It combines fast and flexible design and application of the shopfloor IT with a digital twin, which ensures transparency even in complex production systems.
For the first time ever, Deutsche Messe organizes a Hannover Messe brand event outside of Germany – and Fraunhofer IPK is taking part.
03.09.2018 | Event News
27.08.2018 | Event News
17.08.2018 | Event News
10.09.2018 | Information Technology
10.09.2018 | Information Technology
10.09.2018 | Life Sciences