Stoichiogenomics: the evolutionary ecology of macromolecular elemental composition

Abstract

The new field of 'stoichiogenomics' integrates evolution, ecology and bioinformatics to reveal surprising patterns of the differential usage of key elements [e.g. nitrogen (N)] in proteins and nucleic acids. Because the canonical amino acids as well as nucleotides differ in element counts, natural selection owing to limited element supplies might bias monomer usage to reduce element costs. For example, proteins that respond to N limitation in microbes use a lower proportion of N-rich amino acids, whereas proteome- and transcriptome-wide element contents differ significantly for plants as compared with animals, probably because of the differential severity of element limitations. In this review, we show that with these findings, new directions for future investigations are emerging, particularly via the increasing availability of diverse metagenomic and metatranscriptomic data sets.

Figure 1

Examples of element-based monomer usage bias (MUB) in prokaryotes and eukaryotes. (a) Nitrogen-processing enzymes (blue line) in yeast are unusually low in N compared to the average protein in the proteome (black) and to the average protein involved in sulfur-processing (red) [10], suggesting a form of “element-sparing” in molecules that are most important during limitation by a given element. (b) Protein N content declines with gene expression intensity in plants (green) but not in animals (red) [13], an outcome consistent with the fact that plants likely experience more frequent and sustained direct N limitation than do animals. (c) Proteome N-content in domesticated plants (black bars) and plants associated with N-fixing symbionts (green and black) is similar to that in animals (red) and higher in N-content than proteome N-content in undomesticated plants (green) [15], suggesting that release from selection pressures for N conservation has reduced MUB for N conservation in crop plants. Error bars (standard errors) are very small (max: ~0.001) and thus were not included, as they are not discernible on the plot. (d) The proteins involved in anabolic machinery (spliceosome and ribosomes) are higher in nitrogen content than are the proteins associated with catabolic machinery (proteosome, lysosome, and vacuole) for A. thaliana (green) and H. sapiens (red) [16], a result consistent with an interpretation of N-sparing during nutrient limitation when catabolic processes dominate. (e) In microorganisms, the N:C ratio of a taxon’s proteome is positively correlated with the N:C ratio of its genome [17], suggesting that selection for N conservation may even have been operating during early evolution of the canonical genetic code. Filled circles denote Archaea. Open symbols denote Eubacteria: free-living only, circle; capable of living as animal symbionts, diamond; capable of living as plant symbionts, square; capable of living as animal and plant symbionts, triangle.

Figure 2

N conservation effect size (as a percentage) in the vascular plant Arabidopsis thaliana compared to Homo sapiens and Drosophila melanogaster in DNA, RNA, and proteins [15]. In this analysis, for each molecule the overall monomer N-content in Arabidopsis was compared to the monomer N-content for that molecule averaged for both human and fruit fly. As expected, the apparent magnitude of N conservation in plants vs. animals is weak for the genome (due to base-pairing rules) but is strong for both the transcriptome and for the proteome.

Figure 3

Nitrogen conservation in plants illustrated by lower average N content per nucleotide and shorter sequence length (exons) of UTRs in plants vs animals. The mean and standard errors are plotted per organisms for a set of invertebrate, mammal, and plant species. Sequence data were obtained from the UTResource and species with information from at least 50 genes were selected; number of species for 3’ and 5’ UTRs were as follows: mammals (13 and 16), invertebrates (61 and 43), and plants (81 and 68).