Our goal is to understand how what is happening inside the cell biases the incidence of mutations, affects their persistence, and, ultimately, shapes patterns of natural variation within and between species.
Some of the questions we have been working on include:
- Are genome-wide patterns of variation within and between species linked to chromatin architecture? If so, is this because chromatin organization affects mutation rates or repair dynamics or something else?
- Why do some ostensibly harmful sequence motifs, such as cryptic splice sites, persist in the genome? Are these sites visible to us but invisible to the cell, for example because they are masked by proteins binding nearby?
- How do chaperones affect the evolution of their substrates?
- Are species-specific patterns of sequence evolution related to differences in the repertoire of quality control/repair genes between genomes?
- Does the biased incidence of mutations within a genome make some regions more, others less likely to contribute to adaptive evolution?
We address these questions using a computational approach, combining experimental data on intermolecular interactions – between different proteins, between proteins and RNA, and between proteins and DNA – with structural, kinetic, and of course evolutionary data. With the overarching aim of establishing how the workings of the cell condition the evolutionary process, our research is not tied to a particular biological system. Rather, we flexibly exploit different systems, from humans and yeast to bacteria and archaea, often in a comparative context.
Supek, F., Lehner, B., Hajkova, P., & Warnecke, T. (2014). Hydroxymethylated cytosines are associated with elevated c to g transversion rates. PLoS Genetics, 10 (9).
Warnecke, T., Becker, E. A., Facciotti, M. T., Nislow, C., & Lehner, B. (2013). Conserved substitution patterns around nucleosome footprints in eukaryotes and archaea derive from frequent nucleosome repositioning through evolution. PLoS Computational Biology, 9(11), e1003373+.
Warnecke, T., & Hurst, L. D. (2011). Error prevention and mitigation as forces in the evolution of genes and genomes. Nature Review Genetics, 12(12), 875–881.