Abstract
The native subcellular location (also referred to as localization or cellular compartment) of a protein is the one in which it acts most frequently; it is one aspect of protein function. Do ten eukaryotic model organisms differ in their location spectrum, i.e., the fraction of its proteome in each of seven major cellular compartments? As experimental annotations of locations remain biased and incomplete, we need prediction methods to answer this question. After systematic bias corrections, the complete but faulty prediction methods appeared to be more appropriate to compare location spectra between species than the incomplete more accurate experimental data. This work compared the location spectra for ten eukaryotes: Homo sapiens (human), Gorilla gorilla (gorilla), Pan troglodytes (chimpanzee), Mus musculus (mouse), Rattus norvegicus (rat), Drosophila melanogaster (fruit/vinegar fly), Anopheles gambiae (African malaria mosquito), Caenorhabitis elegans (nematode), Saccharomyces cerevisiae (baker’s yeast), and Schizosaccharomyces pombe (fission yeast). The two largest classes were predicted to be the nucleus and the cytoplasm together accounting for 47–62% of all proteins, while 7–21% of the proteins were predicted in the plasma membrane and 4–15% to be secreted. Overall, the predicted location spectra were largely similar. However, in detail, the differences sufficed to plot trees (UPGMA) and 2D (PCA) maps relating the ten organisms using a simple Euclidean distance in seven states (location classes). The relations based on the simple predicted location spectra captured aspects of cross-species comparisons usually revealed only by much more detailed evolutionary comparisons. Most interestingly, known phylogenetic relations were reproduced better by paralog-only than by ortholog-only trees.
Highlights
Most Proteins Have One Dominant “Native” LocationLocation Spectrum of an OrganismEukaryotic cells contain many distinct compartments separated by membranes
According to the concept of a molecular evolutionary clock introduced by Zuckerkandl and Pauling (Zuckerkandl 1987; Zuckerkandl and Pauling 1962), molecular. Whichever of those views will turn out to be closer to the truth, clearly both solutions provided trees that given the degree of simplicity suggest a stunning similarity between the evolution of species and the spectrum of locations. Another indication for relative robustness of the tree was the observation that the trees generated by DeepLoc and LocTree3 before and after error correction were similar (SOM: Fig. S8 C and D)
When method performance falls below an unspecifiable threshold, trees before and after error correction change substantially (SOM: Fig. S8A)
Summary
Eukaryotic cells contain many distinct compartments separated by membranes. This separation allows to create functionally specialized spaces with slightly different biophysical features (Alberts 2002). The atlas of where proteins predominantly perform their function—their native location or compartment—contains important information about protein function that is used to classify function in the Gene Ontology (GO) Consortium (Ashburner et al 2000) in terms of what is referred to as cellular compartment (here, we used the more commonly used term location, instead). Do we have enough information to describe location for all proteins in entire organisms? If we do, does anything as simple and abstract as the location spectrum contain any relevant information about an organism? If we do, does anything as simple and abstract as the location spectrum contain any relevant information about an organism? If so, this might help to spot sets of proteins most relevant for functional shifts between two organisms
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