PhyloPro - Applications

One of the major uses of PhyloPro is visualizing the evolutionary trajectories of components of biological systems such as protein complexes, signaling or metabolic pathways. Indeed, applying PhyloPro to any protein set, however derived, may provide potentially useful conservation information. Applying PhyloPro, the user is readily able to identify components that are well conserved as well as those that may represent taxon-specific innovations. The ability to subsequently download putative orthologs may also facilitate more in depth phylogenetic analyses. Previously we have successfully applied PhyloPro to investigate patterns of conservation in chromatin remodelling complexes [On et al., 2010], ubiquitin ligase substrates [Persaud et al., 2009] and the extracellular matrix [Cromar et al., in preparation]. Below we illustrate an example where PhyloPro has been used to examine the conservation of 29 proteins associated with glycerophospholipid metabolism biosynthesis in yeast. These proteins were obtained from simply querying the KEGG database resource.

From the above heatmap it is possible to identify several clusters of proteins with similar patterns of conservation. For example, PLB1,2 and 3 (orange cluster) represent sequences that appear specific to fungi. Note that there may indeed be orthologs in other species, however such orthologs are not detectable through our InParanoid pipeline and hence one may deduce that the sequences at the very least have undergone significant divergence in the fungal lineage. On the other hand, proteins in the blue cluster (e.g. PCT1, SPO14 and COS1) appear to have undergone significant expansion within the deuterstomes (species coloured in blue at the top right of the heatmap). Using the colourmap tool available as part of the KEGG database resource, we can map these cluster patterns onto the metabolic map as shown below.

From the above, we see that the highly conserved proteins (yellow, purple and blue enzymes) are associated with maintaining a core set of reactions within the pathway linking to phosphatidyl ethanolamine, phosphatidyl choline, phosphatidyl inositol and phosphatidyl serine. In a similar vein, we mapped conservation profiles of chromatin modification proteins onto their complexes to reveal highly conserved catalytic cores associated with taxon-specific regulatory elements [On et al., 2010].


Persaud, A., Amsen, E.M.,Xiong, X., Wasmuth, J.,Saadon, Z., Fladd, C., Parkinson, J., and Rotin, D. (2009) Comparison of substrate specificity of the ubiquitin ligases Nedd4 and Nedd4-2 using proteome arrays. Molecular Systems Biology. 5:333

On, T., Xiong, X., Pu, S., Turinsky, A., Gong, Y., Emili, A., Zhang, Z., Greenblatt, J., Wodak, SJ. and Parkinson, J. (2010) The evolutionary landscape of the chromatin modification machinery. Proteins. 78:2075-2089

Cromar, C.L. and Parkinson, J. Surveying the Extracellular Matrix: Towards a systems level understanding of its structure, function and evolution. In preparation.

Wan, C., Borgeson, B., Phanse, S., Tu, F., Drew, K., Clark, G., Xiong, X., Kagan, O., Kwan, J., Berzginov, A., Chessman, K., Pal, S., Cromar, G., Papoulas, O., Ni, Z., Boutz, DR., Snejana Stoilova, S., Havugimana, P., Guo, X., Malty, R., Sarov, M., Greenblatt, J., Babu, M., Derry, WB., Tillier, E., Wallingford, J., Parkinson, J., Marcotte, E. and Emili, A. (2015). Panorama of ancient metazoan macromolecular complexes. Nature. 525(7569):339-44.