The essential chemistry of trace elements dictates the molecular speciation and reactivity both within cells and the environment at large. Potentially this promoted the diversification of emerging lineages of Archaea and Bacteria through the establishment of biogeochemical cycles. In contrast structures binding Cu and Zn evolved much later providing further evidence that environmental availability influenced the selection of the elements. The late evolving Zn-binding proteins are fundamental to eukaryotic BCX 1470 cellular biology and Zn bioavailability may have been a limiting factor in eukaryotic evolution. The results presented here provide an evolutionary timeline based on genomic characteristics and key hypotheses can be tested by alternative geochemical methods. < 0.01) greater slopes than Bacteria. Large-scale expansions of Ca-binding protein families have been reported in the larger eukaryotic proteomes (23) and the α >1 power-law scaling extends those trends to both akaryotic superkingdoms. A comparison of the sum of all metal-binding domains and proteome size reveals a remarkable superkingdom-independent scaling (Fig. 1). This finding indicates that the overall gain and loss of metal-binding domains is a fundamental and constant rate for all of life. Furthermore the slope of >1 indicates that the metal-binding proportion of a proteome increases with expansions in proteome size; only ～8.5% of the small proteomes of parasitic Bacteria bind metals whereas >25% of BCX 1470 the largest mammalian proteomes is metal binding (Fig. 1). One caveat might be the lack of complete proteome annotation; 60 to 65% of a given proteome can be structurally characterized with the SUPERFAMILY HMMs yet the BCX 1470 structural genomics initiative suggests that the nonannotated portions of proteomes have a similar proportion of metal-binding domains (24). Fig. 1. Universal power-law scaling in metallomes. The total number of metal-binding domains relative to the total number of structural domains assigned to a given proteome is shown in log-log form as are the fitted power laws from Table S1. Diversity of Metal-Binding Compromises. The different trends for each metal and superkingdom add up to a shared universal trend indicating BCX 1470 the need for diverse compromises. To visualize these compromises we plotted the percent of a proteome that binds the three most abundantly used metals (Fe Zn and Ca) against the total number of protein domains in a proteome for each superkingdom (Fig. 2). In BCX 1470 general Bacteria eschew Ca for Fe and Zn but the choice between the latter two metals depends upon proteome size. Bacteria with small proteomes contain a higher proportion of Zn-binding domains most of them involved in tRNA synthesis transcription and translation (17). The essentiality BCX 1470 of many of these protein domains means that the retention in small genomes is not surprising yet the concomitant exclusion of Fe-binding domains is striking. In contrast larger Bacterial proteomes tend to contain a higher proportion of Fe-binding domains. Similar trends are observed for archaeal proteomes (Fig. 2). Eukaryotic proteomes always contain a greater proportion of Zn-binding structures relative Rabbit polyclonal to ACADS. to those that bind Fe. Ca-binding proteins are often more abundant than Fe-binding proteins particularly in larger eukaryotic proteomes (Fig. 2). Despite these prevailing trends a great diversity of compromises exists within each superkingdom. Essentially life has chosen diversely from the pool of available metalloenzymes but selecting one element requires the relinquishment of another. Fig. 2. Metallomic compromises. The percent of the proteome that binds Zn Fe Ca and the sum of the three metals is shown for (= 0 representing the birth of the protein universe and = 1.0 representing the most recent structural innovation (Fig. 3). The exact order of closely positioned FSFs is potentially debatable in trees of this size but trends across the phylogeny are certainly robust and informative (25). For example Wang et al. examined the evolution of protein architectures specific to each superkingdom and delineated the entire phylogeny into three epochs (19). FSFs ubiquitous to life arose during the first epoch (architectural diversification; = 0-0.391) and these core architectures catalyze much of modern metabolism at least in their modern manifestation (19). The second epoch (superkingdom specification; = 0.391-0.61) describes the evolution of protein.