Research focus

​Some properties of living organisms evolve and diverge at a much higher pace than other traits. Examples range from the molecular composition of the microbial cell surface to the skeletal morphology of dogs. The research of the VIB Laboratory of Systems Biology, K.U.Leuven shows that the mechanisms underlying hyper-evolvable properties often lie at the border between genetics and epigenetics, including such phenomena as chromatin silencing, hyper-variable tandem repeats, transposable elements, telomeric recombination, and hysteresis in regulatory pathways. Hence, one of the primary focuses of the lab is to study these processes, using classic genetic techniques as well as genomics, bioinformatics and mathematical modeling.

It is interesting to note that swift evolution can be seen as a mechanism for “short-term transgenerational memory”. In other words, parental cells can pass on certain information to their progeny, but only for a few generations. In this way, the “memory” stays flexible enough to deal with rapid (external) changes that might require cells to “ignore” the parental “advice”. Hence, we hypothesize that the genetic systems underlying hyper-evolvable traits often developed as a response to hyper-variable selective pressure. This implies that apart from standard genetics and biochemistry, we also incorporate evolution theory to help explain and understand our results.

We focus primarily on the model eukaryote Saccharomyces cerevisiae, although we are also exploring other organisms, often in collaboration with other groups.

In particular, the lab currently focuses on three related topics:

• Telomeres (i.e. the end of chromosomes) are some of the most dynamic and unstable regions in genomes. We study a S. cerevisiae gene family located near the telomeres to investigate how their unique location allows the genes to evolve much more quickly and benefit from both genetic and epigenetic inheritance to coordinate their regulation. Such mechanisms may allow parental cells to pass on information about recent growth conditions to their progeny. Stochastic silencing and desilencing of the telomeric genes allow some cells to “escape” this epigenetic regulation and explore alternative lifestyles.
  
• Yeast cells show an amazing capacity to adhere to various abiotic surfaces, as well as other living cells. However, closely related strains vary widely in their adherence phenotypes. Our research shows that this swift evolution is explained by the fact that the genes underlying adherence contain internal tandem repeat sequences. These repeats are unstable and generate frequent mutation events, leading to altered adherence phenotypes. This might allow pathogens to adhere to novel materials used in today’s medical devices. Moreover, since the variable adhesion proteins are located at the cell surface, the mechanism may also allow cells to elude the host’s immune system. 
  
• Building on the previous project, we are launching a genome-wide survey to investigate how important tandem repeats are as drivers of genetic changes in genomes. We hypothesize that tandem repeats function as hyper-variable genetic modules that confer swift evolution of both coding and regulatory regions. As such, tandem repeats may represent a common but much ignored mechanism of genetic change, besides the much more widely studied single nucleotide polymorphisms (SNPs) and copy number variations (CNVs). Using the S. cerevisiae genome as a model, we use comparative genomics and genetic engineering to explore the physiological role of all tandem repeats in the yeast genome. In addition, through various collaborations, we also explore the importance of repeats in other organisms, including pathogens, plants and humans.