Notwithstanding its long history and compelling motivation, research seeking to explicate the emergence life (EoL) has throughout been a cacophony of unresolved speculation and dispute; absent still any clear convergence or other inarguable evidence of progress. This notwithstanding that it has also produced a rich and varied supply of putatively promising technical advances. Not surprising then the effort being advanced by some to establish a shared basis in fundamental assumptions upon which a more productive community research effort might arise. In this essay however, I press a case in opposition. First, that a chasm divides the rich fauna of contesting EoL models into two conceptually incommensurate classes; here named "chemistry models" (to which class belongs nearly all thinking and work in the field, past and present) and "engine models" (advanced in various more-or-less partial forms by a marginal minority of voices dating from Boltzmann forward). Second, that contemporary non-equilibrium thermodynamics dictates that 'engine-less' (i.e. 'chemistry') models cannot in principle generate non-equilibrium, organized states of matter and are in consequence inherently incapable of prizing life out of inanimate matter.

The second law of thermodynamics leaves no doubt that life on planet Earth and its inherent substantial decrease in entropy is fundamentally based on mechanisms converting environmental free energy into the spatial and temporal order of metabolic processes. This argument holds for present life as much as it does for its very beginnings some 4 billion years ago. In this contribution, we try to strip down free energy conversion in extant life (known as "bioenergetics" to the biologists) to its basic principles with the aim to potentially retrodict the nature of the pre-biotic precursor which drove life into existence. We demonstrate that these basic principles are deeply rooted in aqueous electrochemistry and strongly rely on inorganic redox compounds. The question of life's emergence, generally considered to fall into the realm of organic chemistry, should therefore rather be recognized as an electrochemical problem and its ultimate elucidation will need to strongly implicate the community of electrochemical scientists.

Metal-bearing minerals are an integral part of almost all "metabolism-first"-type scenarios for the emergence of life which consider that life is better defined by what it does than what it is made from. Since metals are formidable catalysts, these scenarios stipulate that early metabolic reactions (and prominently the reduction of CO2 to yield biomass) were performed by (mainly transition) metals contained in certain minerals. Metabolismfirst scenarios stand in opposition to primordial soup hypotheses which envisage prebiotic synthesis of organic molecules as building blocks for life to be the salient feature enabling life to come into being. A critical analysis of the historical roots of these emergence of life hypotheses highlights fundamental inconsistencies prompting us to appeal to basic thermodynamic principles to provide rigorous guidelines for developing contradiction-free models. Combining these guidelines with our present-day understanding of biological energy conversion, arguably the process most fundamental to all life, strongly suggests an expansion of previous mineral-based scenarios to include processes converting environmental redox tensions into phosphate-group-transfer disequilibria, i.e., the quintessential free energy converting mechanism of extant life. Based on their reported physicochemical and electrochemical properties, iron- (together with other transition metal-) based layered double oxyhydroxide (Fe-LDH) minerals such as fougerite are promising candidates to afford the required capacities and therefore may render previous mineral-based scenarios compliant with thermodynamic strictures.

A possibly prominent role for Green Rust minerals in life's emergence is inferred from a comparison of their structural, mechano-dynamic and electrochemical properties and of the layout of bioenergetic, i.e. free energy converting processes in extant organisms. From fundamental thermodynamic considerations, the conversion of environmental free energy into the decrease of entropy that defines life is an indispensable ingredient for life to emerge. A specific scenario for life's emergence mediated by Green Rust minerals in the framework of the alkaline hydrothermal vent hypothesis is proposed.

In the 1930s, Lars Onsager published his famous 'reciprocal relations' describing free energy conversion processes. Importantly, these relations were derived on the assumption that the fluxes of the processes involved in the conversion were proportional to the forces (free energy gradients) driving them. For chemical reactions, however, this condition holds only for systems operating close to equilibrium-indeed very close; nominally requiring driving forces to be smaller than kBT. Fairly soon thereafter, however, it was quite inexplicably observed that in at least some biological conversions both the reciprocal relations and linear flux-force dependency appeared to be obeyed no matter how far from equilibrium the system was being driven. No successful explanation of how this 'paradoxical' behaviour could occur has emerged and it has remained a mystery. We here argue, however, that this anomalous behaviour is simply a gift of water, of its viscosity in particular; a gift, moreover, without which life almost certainly could not have emerged. And a gift whose appreciation we primarily owe to recent work by Prof. R. Dean Astumian who, as providence has kindly seen to it, was led to the relevant insights by the later work of Onsager himself.

We here review the extraordinary mineralogical properties of green rusts and their naturally occurring form, fougerite, and discuss the pertinence of these properties within the alkaline hydrothermal vent (AHV) hypothesis for life's emergence. We put forward an extended version of the AHV scenario which enhances the conformity between extant life and its earliest progenitor by extensively making use of fougerite's mechanistic and catalytic particularities.

The origin and evolution of life comprises a 'ratchet' sequence of disequilibria-driven fluctuation-initiated transitions to states of increasing improbability (complexity) and also of greater efficiency at dissipating the imposed disequilibria. A sequence that is initiated by an extremely simple abiotic seed state and proceeds through an immense sequence of incremental transitions, each vetted on improved dissipation efficiency, yielding an "evolution by creeps" (not initially dependent on "information-encoding" polymers), all the way from rocks to the "tangled bank" and which confers a direct mechanistic, and causal, continuity from the abiotic mechanisms that launched life to those performing like functions in all extant life operating in a precisely orchestrated, spatially organized, dynamically controlled, and integrated network of highly specific transformations. The Alkaline Hydrothermal Vent model of abiogenesis is unique in being consistent with these thermodynamically-based requirements. Explaining e.g., as noted by Nick Lane, why "all cells are powered by proton gradients", and also much else about the most conserved and universal of life's devices

BioEssaysVolume 41, Issue 1 1800208 Thoughts & Opinion Why the Submarine Alkaline Vent is the Most Reasonable Explanation for the Emergence of Life Elbert Branscomb, Corresponding Author Elbert Branscomb brnscmb@illinois.edu University of Illinois, Urbana-Champaign, Carl R. Woese Institute for Genomic Biology, and Department of Physics, 3406 IGB, MC-195, 1206 W. Gregory Drive, Urbana, IllinoisSearch for more papers by this authorMichael J. Russell, Michael J. Russell California Institute of Technology, JPL/NASA, 4800 Oak Grove Drive, M/S 183-601, Pasadena, CaliforniaSearch for more papers by this author Elbert Branscomb, Corresponding Author Elbert Branscomb brnscmb@illinois.edu University of Illinois, Urbana-Champaign, Carl R. Woese Institute for Genomic Biology, and Department of Physics, 3406 IGB, MC-195, 1206 W. Gregory Drive, Urbana, IllinoisSearch for more papers by this authorMichael J. Russell, Michael J. Russell California Institute of Technology, JPL/NASA, 4800 Oak Grove Drive, M/S 183-601, Pasadena, CaliforniaSearch for more papers by this author First published: 15 November 2018 https://doi.org/10.1002/bies.201800208Citations: 14 Response to https://doi.org/10.1002/bies.201800149 Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume41, Issue1January 20191800208 RelatedInformation

Origin of life models based on “energized assemblages of building blocks” are untenable in principle. This is fundamentally a consequence of the fact that any living system is in a physical state that is extremely far from equilibrium, a condition it must itself build and sustain. This in turn requires that it carries out all of its molecular transformations–obligatorily those that convert, and thereby create, disequilibria–using case-specific mechanochemical macromolecular machines. Mass-action solution chemistry is quite unable to do this. We argue in Part 2 of this series that this inherent dependence of life on disequilibria-converting macromolecular machines is also an obligatory requirement for life at its emergence. Therefore, life must have been launched by the operation of abiotic macromolecular machines driven by abiotic, but specifically “life-like”, disequilibria, coopted from mineral precipitates that are chemically and physically active. Models grounded in “chemistry-in-a-bag” ideas, however energized, should not be considered.

Virtually every interesting natural phenomenon, not least life itself, entails physical systems being forced to flow thermodynamically up-hill, away from equilibrium rather than towards it. This requires the action of a mechanism, acting as an “engine”, which lashes the up-hill process to a more powerful one proceeding in its spontaneous, down-hill direction; in this way converting one disequilibrium into another. All organized and dynamic elements of creation, from the galactic to the atomic, can be viewed as powered by, or being the result of, engines of disequilibria conversion; each a link in a great hierarchical cascade of conversions. There is, however, widespread misunderstanding about how disequilibria conversions happen–and indeed about what physically causes them to happen–especially regarding the role of energy and of the physical meaning of free energy. We attempt here to describe and justify what we assert is the correct alternative view of how phenomena are powered in nature, focusing especially on the molecular-level conversion processes (often called “energy conserving”) that power life and that must, then acting in an entirely abiotic context, have driven it first into being.

This paper presents a reformulation of the submarine alkaline hydrothermal theory for the emergence of life in response to recent experimental findings. The theory views life, like other self-organizing systems in the Universe, as an inevitable outcome of particular disequilibria. In this case, the disequilibria were two: (1) in redox potential, between hydrogen plus methane with the circuit-completing electron acceptors such as nitrite, nitrate, ferric iron, and carbon dioxide, and (2) in pH gradient between an acidulous external ocean and an alkaline hydrothermal fluid. Both CO2 and CH4 were equally the ultimate sources of organic carbon, and the metal sulfides and oxyhydroxides acted as protoenzymatic catalysts. The realization, now 50 years old, that membrane-spanning gradients, rather than organic intermediates, play a vital role in life's operations calls into question the idea of "prebiotic chemistry." It informs our own suggestion that experimentation should look to the kind of nanoengines that must have been the precursors to molecular motors-such as pyrophosphate synthetase and the like driven by these gradients-that make life work. It is these putative free energy or disequilibria converters, presumably constructed from minerals comprising the earliest inorganic membranes, that, as obstacles to vectorial ionic flows, present themselves as the candidates for future experiments. Key Words: Methanotrophy-Origin of life. Astrobiology 14, 308-343. The fixation of inorganic carbon into organic material (autotrophy) is a prerequisite for life and sets the starting point of biological evolution. (Fuchs, 2011 ) Further significant progress with the tightly membrane-bound H(+)-PPase family should lead to an increased insight into basic requirements for the biological transport of protons through membranes and its coupling to phosphorylation. (Baltscheffsky et al., 1999 ).

Life is evolutionarily the most complex of the emergent symmetry-breaking, macroscopically organized dynamic structures in the Universe. Members of this cascading series of disequilibria-converting systems, or engines in Cottrell's terminology, become ever more complicated—more chemical and less physical—as each engine extracts, exploits and generates ever lower grades of energy and resources in the service of entropy generation. Each one of these engines emerges spontaneously from order created by a particular mother engine or engines, as the disequilibrated potential daughter is driven beyond a critical point. Exothermic serpentinization of ocean crust is life's mother engine. It drives alkaline hydrothermal convection and thereby the spontaneous production of precipitated submarine hydrothermal mounds. Here, the two chemical disequilibria directly causative in the emergence of life spontaneously arose across the mineral precipitate membranes separating the acidulous, nitrate-bearing CO2-rich, Hadean sea from the alkaline and CH4/H2-rich serpentinization-generated effluents. Essential redox gradients—involving hydrothermal CH4 and H2 as electron donors, CO2 and nitrate, nitrite, and ferric iron from the ambient ocean as acceptors—were imposed which functioned as the original ‘carbon-fixing engine’. At the same time, a post-critical-point (milli)voltage pH potential (proton concentration gradient) drove the condensation of orthophosphate to produce a high energy currency: ‘the pyrophosphatase engine’.

The Submarine Hydrothermal Alkaline Spring Theory for the emergence of life holds that it is the ordered delivery of hydrogen and methane in alkaline hydrothermal solutions at a spontaneously precipitated inorganic osmotic and catalytic membrane to the carbon dioxide and other electron acceptors in the earliest acidulous cool ocean that, through these gradients, drove life into being. That such interactions between hydrothermal fuels and potential oxidants have so far not been accomplished in the lab is because some steps along the necessary metabolic pathways are endergonic and must therefore be driven by being coupled to thermodynamically larger exergonic processes. But coupling of this kind is far from automatic and it is not enough to merely sum the ΔGs of two supposedly coupled reactions and show their combined thermodynamic viability. An exergonic reaction will not drive an endergonic one unless ‘forced’ to do so by being tied to it mechanistically via an organized “engine” of “Free Energy Conversion” (FEC). Here we discuss the thermodynamics of FEC and advance proposals regarding the nature and roles of the FEC devices that could, in principle, have arisen spontaneously in the alkaline hydrothermal context and have forced the onset of a protometabolism. The key challenge is to divine what these initial engines of life were in physicochemical terms and as part of that, what structures provided the first “turnstile-like” mechanisms needed to couple the partner processes in free energy conversion; in particular to couple the dissipation of geochemically given gradients to, say, the reduction of CO2 to formate and the generation of a pyrophosphate disequilibrium. This article is part of a Special Issue entitled: The evolutionary aspects of bioenergetic systems.

Krüppel-type zinc finger (ZNF) motifs are prevalent components of transcription factor proteins in all eukaryotes. KRAB-ZNF proteins, in which a potent repressor domain is attached to a tandem array of DNA-binding zinc-finger motifs, are specific to tetrapod vertebrates and represent the largest class of ZNF proteins in mammals. To define the full repertoire of human KRAB-ZNF proteins, we searched the genome sequence for key motifs and then constructed and manually curated gene models incorporating those sequences. The resulting gene catalog contains 423 KRAB-ZNF protein-coding loci, yielding alternative transcripts that altogether predict at least 742 structurally distinct proteins. Active rounds of segmental duplication, involving single genes or larger regions and including both tandem and distributed duplication events, have driven the expansion of this mammalian gene family. Comparisons between the human genes and ZNF loci mined from the draft mouse, dog, and chimpanzee genomes not only identified 103 KRAB-ZNF genes that are conserved in mammals but also highlighted a substantial level of lineage-specific change; at least 136 KRAB-ZNF coding genes are primate specific, including many recent duplicates. KRAB-ZNF genes are widely expressed and clustered genes are typically not coregulated, indicating that paralogs have evolved to fill roles in many different biological processes. To facilitate further study, we have developed a Web-based public resource with access to gene models, sequences, and other data, including visualization tools to provide genomic context and interaction with other public data sets.

Human chromosome 16 features one of the highest levels of segmentally duplicated sequence among the human autosomes. We report here the 78,884,754 base pairs of finished chromosome 16 sequence, representing over 99.9% of its euchromatin. Manual annotation revealed 880 protein-coding genes confirmed by 1,670 aligned transcripts, 19 transfer RNA genes, 341 pseudogenes and three RNA pseudogenes. These genes include metallothionein, cadherin and iroquois gene families, as well as the disease genes for polycystic kidney disease and acute myelomonocytic leukaemia. Several large-scale structural polymorphisms spanning hundreds of kilobase pairs were identified and result in gene content differences among humans. Whereas the segmental duplications of chromosome 16 are enriched in the relatively gene-poor pericentromere of the p arm, some are involved in recent gene duplication and conversion events that are likely to have had an impact on the evolution of primates and human disease susceptibility.

Chromosome 5 is one of the largest human chromosomes and contains numerous intrachromosomal duplications, yet it has one of the lowest gene densities. This is partially explained by numerous gene-poor regions that display a remarkable degree of noncoding conservation with non-mammalian vertebrates, suggesting that they are functionally constrained. In total, we compiled 177.7 million base pairs of highly accurate finished sequence containing 923 manually curated protein-coding genes including the protocadherin and interleukin gene families. We also completely sequenced versions of the large chromosome-5-specific internal duplications. These duplications are very recent evolutionary events and probably have a mechanistic role in human physiological variation, as deletions in these regions are the cause of debilitating disorders including spinal muscular atrophy.