Statistical Physics and Quantitative Biology
University of Cologne
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Evolution of regulation

Can the complexity of molecular interaction networks account for the bewildering diversity of organisms and species, and for their rapid adaptation to different environments? Interactions between genes are themselves encoded in the genome: Specific proteins (called transcription factors) bind to their corresponding target sites on the DNA, thereby enhancing or reducing the transcription of a nearby gene. Our work on regulation is mainly concerned with fitness effects of regulatory interactions, their inference from genomic data, and their consequences for the evolution of regulation. This work links the biophysics of protein-DNA interactions with the evolution of their biological function. In a recent experimental study, we carry this approach to the fitness landscape of an entire metabolic pathway, which depends on its regulatory sequence and on the environment of the cell. Another recent paper explores the joint fitness effects of nucleosome positioning and regulatory binding sites in the yeast genome.

A segment of regulatory DNA in a eukaryotic cell with many binding sites for various transcription factors (Davidson lab).
Fitness landscape of nucleosome positioning
D. Weghorn and M. Lässig, Proc. Natl. Acad. Sci. 110, 10988–93 (2013)
Formation of regulatory modules by local sequence duplication
A. Nourmohammad and M. Lässig, PLoS Comp. Biol., PLoS Comput Biol 7, e1002167 (12 pages), (2011)
Nonlinear fitness landscape of a molecular pathway
Lilia Perfeito, Stéphane Ghozzi, Johannes Berg, Karin Schnetz, Michael Lässig, PloS Genetics 7, e1002160 (10 pages), (2011)
Energy-dependent fitness: a quantitative model for the evolution of yeast transcription factor binding sites
V. Mustonen, J. Kinney, CG. Callan Jr, and M. Lässig, Proc. Natl. Acad. Sci. 105, 12376-81, (2008)
From biophysics to evolutionary genetics: statistical aspects of gene regulation
M. Lässig, BMC Bioinformatics 8 Suppl 6, S7, (2007)
Evolutionary population genetics of promoters: predicting binding sites and functional phylogenies
V. Mustonen and M. Lässig, Proc. Natl. Acad. Sci. 103, 10967, (2005)
Adaptive evolution of transcription factor binding sites
J. Berg, S. Willmann, and M. Lässig, BMC Evol. Biol. 4, 42, (2004)
Stochastic evolution of transcription factor binding sites
J. Berg and M. Lässig, Biophysics (Moscow) 48, Suppl. 1 (2003)

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