History of Biological Metal Utilization Inferred Through Phylogenomic Analysis of Protein Structures

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History of Biological Metal Utilization Inferred Through Phylogenomic Analysis of Protein Structures History of biological metal utilization inferred through phylogenomic analysis of protein structures Christopher L. Duponta,1, Andrew Butcherb, Ruben E. Valasc, Philip E. Bourned, and Gustavo Caetano-Anollése,1 aMicrobial and Environmental Genomics Group, J. Craig Venter Institute, La Jolla, CA 92121; bDepartment of Biology, University of York, York YO10 5YW, United Kingdom; cBioinformatics Program and dSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, La Jolla, CA 92064; and eEvolutionary Bioinformatics Laboratory, Department of Crop Sciences, University of Illinois, Urbana–Champaign, IL 61801 Edited by Paul G. Falkowski, Rutgers, The State University of New Jersey, New Brunswick, NJ, and approved May 3, 2010 (received for review October 28, 2009) The fundamental chemistry of trace elements dictates the molecular Cu, Zn, and Mo (8, 9). Following the invention of oxygenic speciation and reactivity both within cells and the environment at photosynthesis and the resulting increase in atmospheric O2 large. Using protein structure and comparative genomics, we levels around 2.4 billion years ago (GYA) (10), increased con- elucidate several major influences this chemistry has had upon tinental weathering and oceanic sulfate reduction promoted biology. All of life exhibits the same proteome size-dependent a transition to a euxinic (anoxic and sulfidic) Proterozoic ocean scaling for the number of metal-binding proteins within a proteome. (11, 12). In this high-sulfide, reducing ocean, Fe, Mn, and Co This fundamental evolutionary constant shows that the selection of concentrations would have declined yet remained greatly ele- one element occurs at the exclusion of another, with the eschewal vated relative to the modern oxic ocean, whereas Cu and Zn of Fe for Zn and Ca being a defining feature of eukaryotic pro- would have decreased several orders of magnitude (9). This teomes. Early life lacked both the structures required to control transition was likely not ocean-wide, with sporadic returns to intracellular metal concentrations and the metal-binding proteins anoxia and high spatial variability (13, 14), although coastal that catalyze electron transport and redox transformations. The surface waters perhaps exhibited conditions similar to those of development of protein structures for metal homeostasis coincided the modern oxic ocean. The transition to a generally oxic and fi with the emergence of metal-speci c structures, which predomi- oxidizing ocean (∼0.8–0.5 GYA) prompted large increases in Cu, nantly bound metals abundant in the Archean ocean. Potentially, Zn, and Mo, with concomitant decreases in Fe, Mn, and Co (9). EVOLUTION fi this promoted the diversi cation of emerging lineages of Archaea The enormous redox shifts temporally encompass the evolution and Bacteria through the establishment of biogeochemical cycles. In of modern life, and it has been suggested that this influenced the contrast, structures binding Cu and Zn evolved much later, pro- fl selection of the elements for biological utilization (15), although viding further evidence that environmental availability in uenced there is sparse evidence (16). the selection of the elements. The late evolving Zn-binding proteins The advent of large-scale whole-genome sequencing can help are fundamental to eukaryotic cellular biology, and Zn bioavailabil- elucidate how trace-metal chemistry influenced the evolution of ity may have been a limiting factor in eukaryotic evolution. The protein macromolecules and how the different superkingdoms of results presented here provide an evolutionary timeline based on life incorporated this machinery. Both specific amino acid resi- genomic characteristics, and key hypotheses can be tested by dues and an appropriate 3D arrangement of those residues are alternative geochemical methods. required for proper metal binding by a protein, implying that an analytical approach using protein structure is more appropriate Archean-Proterozoic | biogeochemistry | bioinorganic chemistry | than a purely sequence-based methodology. A recent survey of evolution | metal homeostasis Fe-, Zn-, Mn-, and Co-binding structures in over 300 genome- encoded proteomes revealed that the abundance of proteins etalloproteins contain one or more ions of an inorganic el- binding a specific metal within a proteome scales to proteome Mement in their 3D structure and are said to comprise 30% of size as a power law with distinct slopes (α) for each super- all proteins (1). Many biological pathways contain at least one kingdom and metal (17). Specifically, the proteomes of akaryotes metalloenzyme (2) and consequently require Mg, K, Ca, Fe, Mn, (organisms in superkingdoms Archaea and Bacteria lacking and Zn to sustain life (3). Other elements, like Cu, Mo, Ni, Se, and a nucleus) were described by power laws with values of α > 1 for — — Co, are required by many though not all organismal lineages, Fe-, Mn-, and Co-binding structures, while the eukaryotic pro- and the utilization of trace elements varies greatly between species teomes have values of α > 1 for Zn-binding structures. The fi (3). The different elements have a range of af nities for most different power law slopes for Fe, Mn, Zn, and Co parallels the +2 +2 < +2 < coordinating environments in the order Mg /Ca Mn hypothetical chemical environment in which each superkingdom +2 < +2 < +2 < +2 ∼ +2 Fe Co Ni Cu Zn , an equilibrium series known supposedly evolved, providing full-genome evidence for the in- as the Irving-Williams Series (4). This array of outer-sphere fluence of trace metal geochemistry on biological evolution. chemistry provides significant catalytic diversity, yet has con- In that study, the lack of knowledge about the order of met- sequences for both biological and environmental chemistry. alloenzyme evolution precluded any conclusions about how the Within the cell, metals compete for protein binding sites; hence, chemistry of the different trace metals have impacted the extensive protein networks involving transporters and metal- emergence of diversified life. Although the power-law scaling sensing regulatory proteins are required to maintain the proper revealed a consistent evolutionary trajectory, it lacked direction, subcellular concentrations of each element, and in some cases directly shuttle each metal to its requisite metalloprotein in the proper cellular compartment (1, 5, 6). It has been hypothesized Author contributions: C.L.D., P.E.B., and G.C.-A. designed research; C.L.D., R.E.V., and that the establishment of a metal homeostasis system is required G.C.-A. performed research; A.B. contributed new reagents/analytic tools; C.L.D., R.E.V., for distinct phylotypes of cells to develop (7). P.E.B., and G.C.-A. analyzed data; and C.L.D., P.E.B., and G.C.-A. wrote the paper. Environmentally, for similar fundamental chemical reasons, The authors declare no conflict of interest. the shifts in global redox state hypothesized to have occurred This article is a PNAS Direct Submission. over the past 4.5 billion years (3, 7, 8) greatly influenced trace- 1To whom correspondence may be addressed. E-mail: [email protected] or [email protected]. fi metal abundance. Speci cally, the anoxic and reducing Archean This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10. ocean would have been enriched in Fe, Mn, and Co, yet low in 1073/pnas.0912491107/-/DCSupplemental. www.pnas.org/cgi/doi/10.1073/pnas.0912491107 PNAS | June 8, 2010 | vol. 107 | no. 23 | 10567–10572 Downloaded by guest on September 29, 2021 impeding interpretation over evolutionary history. Here, we ex- binding protein families have been reported in the larger eukaryotic pand upon this previous study by examining a larger set of ele- proteomes (23), and the α >1 power-law scaling extends those trends ments and introduce a temporal scale. The relative timing for the to both akaryotic superkingdoms. evolution of metal-binding protein structures, both those exclu- A comparison of the sum of all metal-binding domains and sive and promiscuous in metal choice, was determined using proteome size reveals a remarkable superkingdom-independent a phylogeny of protein architectures that has been developed and scaling (Fig. 1). This finding indicates that the overall gain and refined over the past 7 years (18, 19). The occurrences and loss of metal-binding domains is a fundamental and constant rate abundances of all of the diverse Fe-, Zn-, Mn-, Co-, Ni-, Cu-, for all of life. Furthermore , the slope of >1 indicates that the Mo-, and Ca-binding protein families in 313 genomes were also metal-binding proportion of a proteome increases with expan- determined. By examining the intersections of these datasets, we sions in proteome size; only ∼8.5% of the small proteomes of identify several genomic fossils that illuminate how trace-metal parasitic Bacteria bind metals, whereas >25% of the largest chemistry has constrained evolution. Environmental concen- mammalian proteomes is metal binding (Fig. 1). One caveat trations of trace metals influenced what type of metal-binding might be the lack of complete proteome annotation; 60 to 65% proteins evolve. The invention of the protein machinery needed of a given proteome can be structurally characterized with the to solve the equilibrium puzzle of the Irving-Williams Series SUPERFAMILY HMMs, yet the structural genomics initiative coincided with the birth of metal-binding electron-transfer pro- suggests that the nonannotated portions of proteomes have teins. Finally, based upon proteome
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