The evolution of actin nucleation - understanding the history of the players
Final Report Abstract
As a part of the DFG priority programme SPP 1464 ‘Principles and evolution of actin nucleator complexes’, this project entitled ‘The evolution of action nucleation – understanding the history of the players’ consisted of two, partly independent packages: (i) unraveling the evolutionary history of proteins involved in actin nucleation and (ii) generating a web based platform enabling their analysis. As the first step, we identified all members of protein families involved in actin nucleation within completely sequenced genomes covering the whole eukaryotic tree of life. Therefore, we developed an automated pipeline which can assist the manual annotation of members of protein families in completed genomes. Next, we reconstructed phylogenetic trees for each of the families to pinpoint gains, losses and duplications. Integrating these results on the tree of life enabled gave us a birds-eye view onto the evolution of actin nucleating protein families. We found that most were already present in the last common ancestor of all eukaryotes and in the following evolution is dominated by rare losses and duplications. From here, we analysed different protein families in more detail. In the case of cordon-bleu, which was so far annotated as vertebrate specific, we could trace homology back to the emergence of the bilateria. Together with Dr. S. Bogdan, we in detail reconstructed the evolution of the Diaphanous protein family, the Diaphanous-related formins and the Drosophila specific WASP homolog Whammy. Finally, we analysed the WH2 domain which enables binding to actin monomers and filaments and is involved in the regulation of actin nucleation. Using highly sensitive Hidden Markov Model based approaches, we were able to identify nearly 500 new members of this domain. When we started to develop the web based platform enabling the analysis of actin nucleation genes, it became clear that we were addressing more general needs of the scientific community. Whereas many different tools exists to analyse gene sets they do not allow an explorative walk through different biological views of the genes and to change the gene lists according to newly upcoming stories. To address this, we developed ISAAC (InterSpecies Analysing Application using Containers). Here, sets can be viewed in the context of genomes, protein functions, protein interactions, pathways, regulation, diseases and drugs. Additionally, users can switch between species with an automatic, orthology based translation of existing gene sets. Furthermore, interaction between different research groups is possible as we provide group based functionalities were sets of genes as well as results of analyses can be exchanged between members of groups.
Publications
- (2013) Formin’ cellular structures. Commun Integr Biol 6: e27634
Bogdan S, Schultz J, Grosshans J
- (2013) The bilaterian roots of cordon-bleu. BMC Res Notes 6: 393
Schultz J, Terhoeven N
- (2014) FHOD proteins in actin dynamics-a formin' class of its own. Small GTPases. 5(2):1-6
Bechtold M, Schultz J, Bogdan S
(See online at https://doi.org/10.4161/21541248.2014.973765) - (2014) ISAAC - InterSpecies Analysing Application using Containers. BMC Bioinformatics 15: 18
Baier H, Schultz J
(See online at https://doi.org/10.1186/1471-2105-15-18) - (2015) Identification of divergent WH2 motifs by HMM-HMM alignments. BMC Research Notes 2015, 8:18
Weiß C, Schultz J
(See online at https://doi.org/10.1186/s13104-015-0981-7)
