We try to gather clues from the genomic data and population studies to form a sound scenario describing the evolutionary history and underlying dynamics of a functional matter. Putting pieces of these puzzles together is usually in the same spirit as a detective investigation which might say something about my photo here.

221B Baker Street, London, UKhttp://www.sherlock-holmes.co.uk/shapeimage_4_link_0
 

Modes of binding site formation: (a) Evolution from independent ancestry and (b) formation by sequence duplication followed by adaptation. 

Evolution of regulatory sequences


Proteins are the dominant functional elements in the living organisms. Most of the variations between the species however are not due to their different protein types but rather the diversified control machinery under which they are employed. Regulatory sequences are pieces of DNA which carry information to control the protein production in a cell. These regions are recognized by certain molecules called transcription factors which influence the DNA-to-Protein decoding process. The structure of these regions varies from a few binding motifs in prokaryotes to modules of dozens of binding sites in eukaryotes. The modular binding regions allow different transcription factors to interact in a combinatorial fashion and regulate gene expression depending on the environmental and cell-specific conditions. We apply methods grounded in statistical physics and information theory to analyze the genomic variations in populations and characterize the evolutionary history of these sequence entities.

Binding site formation in eukaryotes


Formation of regulatory modules with agglomeration of binding sites in a limited evolutionary time span is a question that we have addressed. It turns out that the most of the neighboring sites in multi-cellular eukaryotes have formed from a common sequence ancestor by local duplications. This mode is found to produce regulatory information: duplications can seed new sites in the neighborhood of existing sites.  Duplicate seeds then evolve by subsequent point mutations to the contemporary site sequences. There is no evidence of such frequent local duplication in yeast. This suggests that the pervasive formation of binding sites by local sequence duplication distinguishes

the complex regulatory architecture of higher eukaryotes

from the simpler architecture of uni-cellular organisms.



A. Noumohammad, M. Lässig, PLoS Comp. Biol, PDF

Regulatory complexes and evolution of polygenic loci


As the schematic figure of sea urchin regulatory region suggests, gene expression is influenced by  interactions of multiple binding sites with different transcription factors. Studying the evolution of such polygenic loci requires 1. characterizing protein-sequence interactions and their functional output and

2. inferring the evolutionary forces which have shaped the history of such quantitative trait from the genomic data e.g., polymorphism and divergence. It is natural here to draw analogies with systems of many-particle interactions studied in physics and use similar methods to model the underlying evolutionary dynamics. This turned out to be a really exciting problem.......

A regulatory complex in sea urchin: Multiple sites interacting with different transcription factors (from: E. Davidson)


Publications

                                      


    A. Nourmohammad, M. Lässig, Formation of regulatory modules by local sequence duplication,

    PLoS Comp. Biol., arXiv, PDF 


    RH. Abdolvahhab, F. Roshani, A. Nourmohammad, M. Sahimi and MR. Tabar, Analytical and

    numerical studies of sequence dependence of passage times for translocation of heterobiopolymers

    through nanopores, J. Chem. Phys (2008), PDF


    A. Nourmohammad, M. Lässig, From microsatellite slippage to cis-regulatory module evolution,

    Master thesis, University of Cologne, PDF