All cells contain much more potassium, phosphate, and transition metals than modern (or reconstructed primeval) oceans, lakes, or rivers. Cells maintain ion gradients by using sophisticated, energy-dependent membrane enzymes (membrane pumps) that are embedded in elaborate ion-tight membranes. The first cells could possess neither ion-tight membranes nor membrane pumps, so the concentrations of small inorganic molecules and ions within protocells and in their environment would equilibrate. Hence, the ion composition of modern cells might reflect the inorganic ion composition of the habitats of protocells. We attempted to reconstruct the “hatcheries” of the first cells by combining geochemical analysis with phylogenomic scrutiny of the inorganic ion requirements of universal components of modern cells. These ubiquitous, and by inference primordial, proteins and functional systems show affinity to and functional requirement for K ⁺ , Zn ²⁺ , Mn ²⁺ , and phosphate. Thus, protocells must have evolved in habitats with a high K ⁺ /Na ⁺ ratio and relatively high concentrations of Zn, Mn, and phosphorous compounds. Geochemical reconstruction shows that the ionic composition conducive to the origin of cells could not have existed in marine settings but is compatible with emissions of vapor-dominated zones of inland geothermal systems. Under the anoxic, CO ₂ -dominated primordial atmosphere, the chemistry of basins at geothermal fields would resemble the internal milieu of modern cells. The precellular stages of evolution might have transpired in shallow ponds of condensed and cooled geothermal vapor that were lined with porous silicate minerals mixed with metal sulfides and enriched in K ⁺ , Zn ²⁺ , and phosphorous compounds.

Cell cytoplasm of archaea, bacteria, and eukaryotes contains substantially more potassium than sodium, and potassium cations are specifically required for many key cellular processes, including protein synthesis. This distinct ionic composition and requirements have been attributed to the emergence of the first cells in potassium-rich habitats. Different, albeit complementary, scenarios have been proposed for the primordial potassium-rich environments based on experimental data and theoretical considerations. Specifically, building on the observation that potassium prevails over sodium in the vapor of inland geothermal systems, we have argued that the first cells could emerge in the pools and puddles at the periphery of primordial anoxic geothermal fields, where the elementary composition of the condensed vapor would resemble the internal milieu of modern cells. Marine and freshwater environments generally contain more sodium than potassium. Therefore, to invade such environments, while maintaining excess of potassium over sodium in the cytoplasm, primordial cells needed means to extrude sodium ions. The foray into new, sodium-rich habitats was the likely driving force behind the evolution of diverse redox-, light-, chemically-, or osmotically-dependent sodium export pumps and the increase of membrane tightness. Here we present a scenario that details how the interplay between several, initially independent sodium pumps might have triggered the evolution of sodium-dependent membrane bioenergetics, followed by the separate emergence of the proton-dependent bioenergetics in archaea and bacteria. We also discuss the development of systems that utilize the sodium/potassium gradient across the cell membranes.

An analysis of the distribution of the Na⁺-translocating ATPases/ATP synthases among microbial genomes identified an atypical form of the F₁F_o-type ATPase that is present in the archaea Methanosarcina barkeri and M.acetivorans, in a number of phylogenetically diverse marine and halotolerant bacteria and in pathogens Burkholderia spp. In complete genomes, representatives of this form (referred to here as N-ATPase) are always present as second copies, in addition to the typical proton-translocating ATP synthases. The N-ATPase is encoded by a highly conserved atpDCQRBEFAG operon and its subunits cluster separately from the equivalent subunits of the typical F-type ATPases. N-ATPase c subunits carry a full set of sodium-binding residues, indicating that most of these enzymes are Na⁺-translocating ATPases that likely confer on their hosts the ability to extrude Na⁺ ions. Other distinctive properties of the N-ATPase operons include the absence of the delta subunit from its cytoplasmic sector and the presence of two additional membrane subunits, AtpQ (formerly gene 1) and AtpR (formerly gene X). We argue that N-ATPases are an early-diverging branch of membrane ATPases that, similarly to the eukaryotic V-type ATPases, do not synthesize ATP. Contact:galperin@ncbi.nlm.nih.gov; amulkid@uos.de Supplementary information: Supplementary data are available at Bioinformatics online.

Summary: While certain archaea appear to synthesize and/or metabolize fatty acids, the respective pathways still remain obscure. By analysing the genomic distribution of the key lipid‐related enzymes, we were able to identify the likely components of the archaeal pathway of fatty acid metabolism, namely, a combination of the enzymes of bacterial‐type β ‐oxidation of fatty acids [acyl‐coenzyme A ( CoA ) dehydrogenase, enoyl‐ CoA hydratase and 3‐hydroxyacyl‐ CoA dehydrogenase] with paralogs of the archaeal acetyl‐ CoA C ‐acetyltransferase, an enzyme of the mevalonate biosynthesis pathway. These three β ‐oxidation enzymes working in the reverse direction could potentially catalyse biosynthesis of fatty acids, with paralogs of acetyl‐ CoA C ‐acetyltransferase performing addition of C ₂ fragments. The presence in archaea of the genes for energy‐transducing membrane enzyme complexes, such as cytochrome bc complex, cytochrome c oxidase and diverse rhodopsins, was found to correlate with the presence of the proposed system of fatty acid biosynthesis. We speculate that because these membrane complexes functionally depend on fatty acid chains, their genes could have been acquired via lateral gene transfer from bacteria only by those archaea that already possessed a system of fatty acid biosynthesis. The proposed pathway of archaeal fatty acid metabolism operates in extreme conditions and therefore might be of interest in the context of biofuel production and other industrial applications.