“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:
- How does gene regulatory logic differ between eukaryotes, bacteria, and archaea? Can we use archaea as models to understand incipient complexity in histone-based gene regulation? (Rojec et al 2019 eLife; Hocher et al 2019 eLife)
- How do chaperones (and RNA chaperones in particular) affect the evolution of their substrates? Can we deploy RNA chaperones as tools to enhance the evolvability of ribozymes? (Rudan et al 2015 eLife)
- What is the physiological and evolutionary impact of one of the best-characterized substrate classes of RNA chaperones: self-splicing introns? (Rudan et al 2018 eLife; Repar et al 2017 Genetics)
- How do different DNA modifications affect mutation rates and genome evolution? (Supek et al 2014 PLoS Genetics)
- 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? (Warnecke et al 2013 PLoS Comp Biol; Warnecke et al 2012 PLoS Comp Biol; Warnecke et al 2008 PLoS Genetics)
We address these questions using both computational and experimental approaches. This often involves combining genome-wide 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.
Hocher A, Rojec M, Swadling JB, Esin A, Warnecke T. (2019). The DNA-binding protein HTa from Thermoplasma acidophilum is an archaeal histone analog. eLife, e52542
Rojec M, Hocher A, Stevens KM, Merkenschlager M, Warnecke T. (2019). Chromatinization of Escherichia coli with archaeal histones. eLife, e49038
Esin A, Bergendahl LT, Savolainen V, Marsh JA, Warnecke T. (2018). The genetic basis of red blood cell sickling in deer. Nature Ecology & Evolution 2(2), 367-376.
Rudan M, Bou Dib P, Musa M, Kanunnikau M, Sobočanec S, Rueda D, Warnecke T, Krisko A. (2018). Normal mitochondrial function in Saccharomyces cerevisiae has become dependent on inefficient splicing. eLife e35330.
Ruden M, Schneider D, Warnecke T, Krisko A. (2015). RNA chpaerones buffer deleterious mutations in E. coli. eLife (4), e04745.