Abstract
BackgroundProteins play a key role in cellular life. They do not act alone but are organised in complexes. Throughout the life of a cell, complexes are dynamic in their composition due to attachments and shared components. Experimental and computational evidence indicate that consecutive addition and secondary losses of components played a major role in the evolution of some complexes, mostly without affecting the core function. Here, we analysed in a large scale approach whether this flexibility in evolution is only limited to a distinct number of complexes or represents a more general trend.ResultsFocussing on human protein complexes, we based our analysis on a manually curated dataset from HPRD. In total, 1,060 complexes with 6,136 proteins from 2,187 unique genes were considered. We computed interologs in 25 different species and predicted the composition of complexes. Over the analysed species, the composition of most complexes was highly flexible and only 25% of all genes were never lost. Even if one component was lost at a particular point in time, the fraction of observed second, independent losses of additional components was high (75% of all complexes affected). Still, loss of whole complexes happened rarely. This biological signal deviated significantly from random models. We exemplified this trend on the anaphase promoting complex (APC) where a core is highly conserved throughout all metazoans, but flexibility in certain components is observable.ConclusionConsecutive additions and losses of distinct units is a fundamental process in the evolution of protein complexes. These evolutionary events affecting genes coding for units in human protein complexes showed a significantly different phylogenetic pattern compared to randomly selected genes. Determination of taxon specific attachments or losses might be linked to specific cellular or morphological features. Thus, protein complexes contain not only structural and functional, but also evolutionary cores.
Highlights
Proteins play a key role in cellular life
A parsimony based approach for inferring the evolutionary history of protein complexes We focussed our analysis on human protein complexes annotated in the human protein reference database (HPRD), as this database is manually curated and, of high quality [9]
At the time of the analysis, the HPRD dataset contained 2,197 distinct genes which were found in 1,060 protein complexes
Summary
Proteins play a key role in cellular life. They do not act alone but are organised in complexes. Most of these shared components are associated peripherally and are not integral members of the complexes suggesting a role in the regulation of molecular-machines [6] Complementary to this network view, protein complexes can be partitioned in a core which is modulated by different attachments. Isoforms of a complex are built, possibly with slightly different functions Some of these attachments, which can consist of multiple proteins itself, can be connected to different core complexes. These mobile regulatory units are often called modules [1]. The combination of core functional units with variably attached modules increases the number of different complexes and thereby the complexity of the cell. This could be interpreted as an 'ortholog proteome' that resembles the backbone necessary to facilitate fundamental functions of an eukaryotic cell [7]
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