What makes species unique? The contribution of proteins with obscure features

Abstract

Background: Proteins with obscure features (POFs), which lack currently defined motifs or domains, represent between 18% and 38% of a typical eukaryotic proteome. To evaluate the contribution of this class of proteins to the diversity of eukaryotes, we performed a comparative analysis of the predicted proteomes derived from 10 different sequenced genomes, including budding and fission yeast, worm, fly, mosquito, Arabidopsis, rice, mouse, rat, and human.

Results: Only 1,650 protein groups were found to be conserved among these proteomes (BLAST E-value threshold of 10(-6)). Of these, only three were designated as POFs. Surprisingly, we found that, on average, 60% of the POFs identified in these 10 proteomes (44,236 in total) were species specific. In contrast, only 7.5% of the proteins with defined features (PDFs) were species specific (17,554 in total). As a group, POFs appear similar to PDFs in their relative contribution to biological functions, as indicated by their expression, participation in protein-protein interactions and association with mutant phenotypes. However, POF have more predicted disordered structure than PDFs, implying that they may exhibit preferential involvement in species-specific regulatory and signaling networks.

Conclusion: Because the majority of eukaryotic POFs are not well conserved, and by definition do not have defined domains or motifs upon which to formulate a functional working hypothesis, understanding their biochemical and biological functions will require species-specific investigations.

Figure 1

Representation of POFs in 10 different eukaryotic genomes. POFs represent 18% to 38% of the proteins in 10 different eukaryotic proteomes (S. cerevisiae, Sc; S. pombe, Sp; A. thaliana, At; O. sativa, Os; D. melanogaster, Dm; A. gambiae, Ag; M. musculus, Mm; R. norvegicus, Rn; H. sapiens, Hs; C. elegans, Ce). Proteomes were obtained and analyzed as described in Materials and methods.

Figure 2

POFs are more divergent than PDFs in different eukaryotic proteomes.(a) Relative similarity among PDFs and POFs in S. cerevisiae (Sc) and S. pombe (Sp). (b) Relative similarity among PDFs and POFs in M. musculus (Mm) and R. norvegicus (Rn). (c) Relative similarity among total or essential PDFs and POFs in S. cerevisiae (Sc) and C. elegans (Ce). BLAST comparisons were performed as described in Materials and methods.

Figure 3

POFs are more likely to be species specific than PDFs. POFs are more likely to be species specific than PDFs among 10 different proteomes (S. cerevisiae, Sc; S. pombe, Sp; A. thaliana, At; O. sativa, Os; D. melanogaster, Dm; A. gambiae, Ag; M. musculus, Mm; R. norvegicus, Rn; H. sapiens, Hs; C. elegans, Ce). (a) Proportion of POFs and PDFs represented in unique protein sets determined among the 10 different proteomes. Specificity of a protein to a particular proteome was determined based on a BLAST e-value cutoff of 10^-6. Numbers on top of bars donate the total number of proteins in each group. (b) Relationship trees among the 10 different proteomes shown in (a). Trees were constructed based on PDFs (dashed blue line) or POFs (red line). Proteome analyses, BLAST comparisons and tree construction were performed as described in Materials and methods. Outl., an outlier E.coli genome was used.

Figure 4

Relative contribution of POFs to biological functions. (a) Representation of POFs in EST libraries from different organisms (A. thaliana, At; O. sativa, Os; D. melanogaster, Dm; A. gambiae, Ag; M. musculus, Mm; R. norvegicus, Rn; C. elegans, Ce; H. sapiens, Hs). (b) Representation of POFs in protein-protein interaction networks in Sc and Ce. (c) Percent phenotypic penetrance of PDFs and POFs in Sc. EST libraries, protein-protein interaction data, insertional mutagenesis data, and sequence comparisons were obtained/performed as described in Materials and methods.

Figure 5

Distinct differences in several biophysical characteristics between POFs and PDFs. A comparison of PDFs and POFs shows distinct differences in several biophysical characteristics (S. cerevisiae, Sc; S. pombe, Sp; A. thaliana, At; O. sativa, Os; D. melanogaster, Dm; A. gambiae, Ag; M. musculus, Mm; R. norvegicus, Rn; H. sapiens, Hs; C. elegans, Ce). (a) Average length of PDFs and POFs from different species. (b) Structural disorder index (disorder/length) of PDFs and POFs from different species. (c) Hydrophilic index of PDFs and POFs from different species. Proteomes analyses were performed as described in Materials and methods.