Global analysis of predicted proteomes: functional adaptation of physical properties

Abstract

The physical characteristics of proteins are fundamentally important in organismal function. We used the complete predicted proteomes of >100 organisms spanning the three domains of life to investigate the comparative biology and evolution of proteomes. Theoretical 2D gels were constructed with axes of protein mass and charge (pI) and converted to density estimates comparable across all types and sizes of proteome. We asked whether we could detect general patterns of proteome conservation and variation. The overall pattern of theoretical 2D gels was strongly conserved across all life forms. Nevertheless, coevolved replicons from the same organism (different chromosomes or plasmid and host chromosomes) encode proteomes more similar to each other than those from different organisms. Furthermore, there was disparity between the membrane and nonmembrane subproteomes within organisms (proteins of membrane proteomes are on the average more basic and heavier) and their variation across organisms, suggesting that membrane proteomes evolve most rapidly. Experimentally, a significant positive relationship independent of phylogeny was found between the predicted proteome and Biolog profile, a measure associated with the ecological niche. Finally, we show that, for the smallest and most alkaline proteomes, there is a negative relationship between proteome size and basicity. This relationship is not adequately explained by AT bias at the DNA sequence level. Together, these data provide evidence of functional adaptation in the properties of complete proteomes.

Fig. 1.

Theoretical 2D gels. (A) Scatter-plot (theoretical 2D gel) of the fruitfly Drosophila melanogaster. (B) The corresponding density plot as used in the analyses. Similar patterns are shown by bacteria (C), archaea (D), and plasmids containing orders of magnitude fewer proteins (E and F).

Fig. 3.

Proteome subsets compared within and between organisms. Points are means and SE bars of comparisons between all pairs of proteomes. For the plasmid and mitochondrial data, all comparisons between proteomes from a particular pair of organisms were averaged before inclusion.

Fig. 2.

Alternative theoretical 2D gels. (A) Typical two-winged theoretical 2D gel showing yeast (S. cerevisiae). (B) Randomization of amino acids among yeast proteins. The distribution is similarly bimodal, but significantly different, particularly in its narrower spread of pI. (C and D) Division of the yeast proteome into membrane and nonmembrane subsections. As with all other proteomes, the membrane proteome is more basic. (E) The E. coli membrane subproteome showing much greater basic bias than in yeast. (F) One of the smallest proteomes showing a similarly basic biased proteome.

Fig. 4.

Two comparisons were made independently for each pair organisms, one between membrane subproteomes and one between nonmembrane subproteomes. Each spot corresponds to the results for a pair of organisms: the x axis is the similarity of the membrane subproteomes; the y axis is the difference between the two subproteome comparisons.

Fig. 5.

Phylogenetically independent relationship between theoretical 2D gels and Biolog profile, a proxy for ecological niche. Each point corresponds to comparisons (independent contrasts) between two taxa for differentiation in theoretical 2D gel (defined as 1 - the proteome correlation used elsewhere) and Biolog profile differentiation. The taxa compared in each point are those branching from the numbered node in the phylogeny shown in Fig. 7. The line is a least-squares fit through the origin.

Fig. 6.

Relationships of proteome pI among the smallest, most basic proteomes (•, bacteria; ×, eukaryotes; +, archaea). (A) Relationship with size across complete proteomes. Only the organisms shown in this graph feature in subsequent graphs. (B) Relationship with total DNA compositional bias. (C) Relationship with the ratio of arginine (the basic amino acid with high GC in its codons) to lysine and tyrosine (the basic amino acids with high AT in their codons). (D) The relationship with proteome size among membrane proteomes.