Modern proteomes contain putative imprints of ancient shifts in trace metal geochemistry

Abstract

Because of the rise in atmospheric oxygen 2.3 billion years ago (Gya) and the subsequent changes in oceanic redox state over the last 2.3-1 Gya, trace metal bioavailability in marine environments has changed dramatically. Although theorized to have influenced the biological usage of metals leaving discernable genomic signals, a thorough and quantitative test of this hypothesis has been lacking. Using structural bioinformatics and whole-genome sequences, the Fe-, Zn-, Mn-, and Co-binding metallomes of 23 Archaea, 233 Bacteria, and 57 Eukarya were constructed. These metallomes reveal that the overall abundances of these metal-binding structures scale to proteome size as power laws with a unique set of slopes for each Superkingdom of Life. The differences in the power describing the abundances of Fe-, Mn-, Zn-, and Co-binding proteins in the proteomes of Prokaryotes and Eukaryotes are similar to the theorized changes in the abundances of these metals after the oxygenation of oceanic deep waters. This phenomenon suggests that Prokarya and Eukarya evolved in anoxic and oxic environments, respectively, a hypothesis further supported by structures and functions of Fe-binding proteins in each Superkingdom. Also observed is a proliferation in the diversity of Zn-binding protein structures involved in protein-DNA and protein-protein interactions within Eukarya, an event unlikely to occur in either an anoxic or euxinic environment where Zn concentrations would be vanishingly low. We hypothesize that these conserved trends are proteomic imprints of changes in trace metal bioavailability in the ancient ocean that highlight a major evolutionary shift in biological trace metal usage.

Fig. 1.

Power low scaling of metal-binding domains. (A) Log-log plot of the abundances of Zn-binding domains in Archaea (black ■), Bacteria (red x), and Eukarya (blue o) compared with the total number of structural domains in a proteome. Each point represents the number of metal-binding domains and the total number of assigned protein domains in a discrete proteome. The total number of structural domains annotated in a proteome scales linearly to both genome size and gene number (Fig. 6, which is published as supporting information on the PNAS web site). Also shown are the fitted power laws (black solid, Archaea; red dashed, Bacteria; blue dotted, Eukaryotes). (B) The power law slopes describing the abundances of Fe-, Zn-, Mn-, and Co/B₁₂-binding structural domains in the proteomes of Archaea (black), Bacteria (red), and Eukarya (blue). The error bars denote 1 SD. The statistics for the quality of the power law fits are shown in Table 1. When the slopes of the curves are compared, they are significant as follows (A, Archaea; B, Bacteria; E, Eukaryote): Zn, all are significantly different at α = 0.5%. Fe, B vs. A and B vs. E α = 0.1%, A vs. E α = 5%. Mn, A vs. E, B vs. E α = 0.5%, A vs. B, not significantly different at α = 5%. Co, A vs. E α = 1%, B vs. E α = 5%, A vs. B not significantly different at α = 5%.

Fig. 2.

Diversity and abundance of Fe-binding fold families in Bacteria. For each Fe-binding fold family (tick marks on x axis), the red × (left axis for scale) shows the percentage of proteomes in which it occurs, whereas the blue ♦ (right axis for scale) shows the average copy number in proteomes where it does occur. The shaded area highlights the number of fold families that occur in at least 50% of the Bacterial proteomes examined. Similar trends are observed for the other metals and Superkingdoms.

Fig. 3.

The abundance and diversity of “small protein” class Zn-binding structures. (A) Log-log plot of the abundance of Zn-binding domains belonging to the “small protein” structural class in proteomes of Archaea, Bacteria, and Eukarya (symbols are the same as in Fig. 1). (B) The phylogenetic distribution of “small protein” class Zn-binding fold families. There are 53 distinct “small protein” class Zn-binding fold families that occur in at least one proteome, and the distribution of these is described by the top set of numbers in each set. The bottom numbers of each set detail distribution of fold families that occur in at least 50% of the proteomes of a Superkingdom (28 “small protein” class Zn-binding fold families occur in at least 50% of the proteomes of at least one Superkingdom). The lists of FFs in each category within the diagram are provided in Table 8, which is published as supporting information on the PNAS web site.