Genomic and phenotypic changes are strongly intertwined. The genome encodes the molecular machinery of a species. In turn this molecular machinery co-determines traversable paths through changing fitness landscapes and thus which genomic variations are more likely to be fixated in evolution. Here we elucidate the interplay between genomic evolution and protein function: how do functional properties of proteins translate into selective constraints? How is this reflected in the way that the molecular machinery is shaped by genomic events?
Recent large-scale functional studies in eukaryotic organisms allow us to define the function of a protein in terms of its interactions with other proteins. Moreover, the availability of a large number of completely sequenced eukaryotic genomes permits the comparison of comprehensive parts lists of the molecular machinery between different species using protein families. Changes in the size of a protein family typically occur through invention, loss or duplication of genes. We connect these evolutionary events to the functional relations of the proteins that belong to this family. If a protein is lost, is the entire subsystem (e.g. protein complex) lost? Is the protein replaced? If a protein has duplicated, do both daughter proteins perform part of the ancestral function? Do they typically gain new functionalities as well? Literature supplies examples of almost any imaginable scenario but we need to extend beyond indivual examples to provide rules of thumb that can be used when there is no experimental data available.
A common approach in all our research is to integrate large-scale genomic- with large-scale functional data: in order to uncover broad evolutionary trends we generalize over many species and many cellular subsystems. We study individual examples in more detail to test our interpretations of the results obtained from the large-scale comparisons.
I currently work on the evolution of Fusarium oxysporum at the group of Martijn Rep that is part of the Molecular Plant Pathology group at the SILS, University of Amsterdam.
Fokkens L, Hogeweg P, Snel B
Gene duplications contribute to the overrepresentation of interactions between proteins of a similar age.
BMC Evolutionary Biology (2012) Abstract
Van Wageningen S, Kemmeren P, Lijnzaad P, Margaritis T, Benschop JJ , de Castro IJ, Van Leenen D, Groot Koerkamp MJA, Ko CW, Miles AJ, Brabers N, Brok MO, Lenstra TL, Fiedler D , Fokkens L, Aldecoa R, Apweiler E, Taliadouros V, Sameith K, Van de Pasch LAL, Van Hooff SR, Bakker LV, Krogan NJ, Snel B, Holstege FCP
Functional overlap and regulatory links shape genetic interactions between signaling pathways.
Cell 143(6):991-1004 (2010)
Fokkens L, Botelho SM, Boekhorst J, Snel B
Enrichment of homologs in insignificant BLAST hits by co-complex network alignment.
BMC Bioinformatics (2010) Full text
Fokkens L, Snel B
Cohesive versus flexible evolution of functional modules in eukaryotes.
PLoS Computational Biology (2009) Full text
Franke L, van Bakel H, Fokkens L, de Jong ED, Egmont-Petersen M, Wijmenga C
Reconstruction of a functional human gene network, with an application for prioritizing positional candidate genes.
American Journal of Human Genetics (2006) Full text