Living organisms change and evolve because of mutations in their DNA. Recent findings suggest that some DNA sequences are hypervariable and evolvable , while others are extremely robust and remain constant over evolutionary timescales. The long-term goal of our research is to combine theory and experiments to investigate the molecular mechanisms underlying genetic robustness and evolvability. Apart from the fundamental aspects, we also plan to explore practical facets, including swift evolution of pathogens and construction of hypervariable modules for synthetic biology. In this proposal we focus on one specific topic, namely the role of tandem repeats as hypervariable modules in genomes. Tandem repeats are short DNA sequences that are repeated head-to-tail. Such repeats have traditionally been considered as non-functional junk DNA and they are therefore mostly ignored. However, our ongoing research shows that tandem repeats often occur in coding and regulatory sequences. The repeats show mutation rates that are 10 to 10.000 fold higher than mutation rates in the rest of the genome. These frequent mutations alter the function and/or expression of genes, allowing organisms to swiftly adapt to novel environments. Hence, repeats may be a common mechanism for organisms to generate potentially beneficial variability in certain regions of the genome, while keeping other regions stable and robust (Rando and Verstrepen, Cell 128: 655; Verstrepen et al., Nature Genetics 37: 986; Verstrepen et al., Nature Microbiol. 2: 15). We propose a multidisciplinary systems approach to unravel the biological role of repeats. First, we will use bioinformatics to screen various model genomes and identify, categorize and analyze all tandem repeat loci in the model eukaryote Saccharomyces cerevisiae. Using this data, we will select a subset of repeats and apply experimental techniques to investigate the functional consequences of mutations in these repeats.
Fields of science
Call for proposal
See other projects for this call