Introduction

Ernesto DI MAURO

Institute of Molecular Biology and Pathology, CNR, Rome, Italy

Origin of life studies are an active field whose borders are poorly defined. It allows us to approach the problem with intellectual freedom, out of the limitations imposed by sclerotized disciplines. This book proposes fly-over of this large territory and an in-depth eagle-eyed look of the opinions and the results obtained by some among the active contributors of this fascinating and deeply thought-provoking matter. The topics are presented as usual according to a bottom-up order: the habitability of the Universe, the rationale behind meaningful prebiotic chemistry, the possible and the probable prebiotic chemical frames, the problem of chirality, the role of minerals in biogenesis, the biogenic fertile environments, the in-and-out problem as solved by vesicles physics, the way of the codes, LUCA and protometabolisms, the meaning of complex biological biomorphs (read: viroids). The evolution of information and complexity is the background scenario, which accompanies all of this reasoning.

A single standard-sized book provides a limited space, and in this context 10 chapters are a meagre body. Potential, appropriate and relevant contributors could have been and could be many more. Hence, the effort by each of the authors to widen the field of their descriptions, trying to amend the complexity of this dynamic and multifaceted science.

Connecting cosmology with molecular biology may seem arrogant, but it is not so. The length of the road is the precise indication that we are confronted with an enormous problem that can only be addressed with humility. The daring endeavor is to try to unify under the same perspective topics and discoveries made in very different fields, often told in languages which sometimes are difficult to reconcile. The reader will, in the end, realize that a solid synthesis is for the moment lacking but that, at the same time, the thread connecting the Big Bang to our existence is beginning to become traceable.

Another important message conveyed by the pages of this book is that the approach to the origin of life should be as devoid as possible of anthropocentry. The Universe does not really care for the fact that the leaves will fall from the tree of my garden at due time and "I" will die. But, at the same time, the Universe takes into consideration that life exists, that life is one of its epiphanies. Here, on this planet and as far as we know, life is a continuous uninterrupted and internally interconnected process. Life is a category of phenomena that can be interpreted only if we look at it with the necessary aloofness.

In order to emerge, life requires stability, simplicity and reactivity. It also entails complexity. The recognition of the necessity of these properties is necessarily accompanied by a series of question marks.

Stability

"Something came from nothing because it was more stable than nothing" (Stenger 2006). The uncontroversial truth contained in this aphorism by Victor Stenger applies to the evolution of the organization of matter in the whole Universe which, for what concerns us here, comes out from the Big Bang. In particular, and even more so, this concept applies also to life. A telling example is provided by polymers which, most of the time, are a stabilization form of the monomers that compose it.

As a side product of this forced and directed tendence to stability, internally repetitive structures are produced, which are thus able to elaborate information. They do so by introducing and selecting small variations. This process, in biological terms, is dubbed evolution. Is this an intrinsic property of polymers? It is so only for some of them, and if so which ones? Only for those which undergo repeated cycles of synthesis/degradation? Variations usually and typically occur within the same class of molecules: one amino acid to another amino acid in a peptide chain, and one nucleic base to another nucleic base in RNA or DNA. Evolution is the evolution of information.

A short-term sort of variation is that occurring in the so-called metabolic cycles. Remaining in textbook examples and in a central gear of the machinery (the Krebs cycle), a compound, say citrate, "changes" under the effect of the environment and becomes cis-aconitate, which becomes D-isocitrate, which becomes alfa-ketoglutarate, then succinyl-CoA, and succinatate, fumarate, L-malate, oxaloacetate, which again becomes citrate. But in the meantime, mediated by the interaction with the environment and with ancillary molecules, something "vital" has occurred and, depending on the direction of rotation of the cycle, the transfer of energy or carbon has orderly entered the system. The prebiotic valence, the determination of the whereabouts of these cycles and the possibility of their reconstruction are becoming experimented reality (Muchowska et al. 2019; Isnard and Moran 2020; Preiner et al. 2020; Yadav et al. 2022).

A long-standing debate has dominated the scene of origin of life studies: "genetics-first" or "metabolism-first"? Occasionally, also "membranes-first" accompanied the bias. The answers to these initially reasonable questions found their well-grounded advocates, but it gradually became clear that no real distinction was possible, and that without a system to harness and control energy (a system that is one of the incarnations of the concept of "phenotype"), no replication and transmission of the genotype might have been possible. With no genotype, the phenotype would have succumbed to the laws of disorder and the domination by local conditions. Hence, the necessity of the simultaneous, concurrent and cooperative evolution of both phenotype and genotype, of both nucleic acids and proteins, and of carboxylic acids, all contained in membrane-defined spaces where concentrations and selections could take place. The prebiotic chemistry involved was thus necessarily large-spectrum, and no solitary, selective and fastidious synthesis would have been likely to win the race.

The history of the evolution of the interaction of the RNA world with the protein world goes through appealing and elegantly solved chapters. The structure of the huge ribosome machinery, as determined by the 2009 Nobel Laureates Venkatraman Ramakrishnan, Thomas A. Steitz and Ada E. Yonath, still conserves in its central RNA core the signs of its initial function of peptide-bond maker. The story of the evolution of ribosomes (Yonath 2010; Belousoff et al. 2010; Petrov et al. 2014; Bose et al. 2022) shows how proteins structurally and functionally gradually replaced RNAs. The extant universal presence of protein enzymes has the same evolutionary history consisting of substitution of the functions initially performed by RNA catalysts. Omnipresent ribo cofactors as NAD are there to remind us. A big part of this story is still unknown. The possibilities of proteins of acquiring independence from nucleic codes are well summarized in Foden et al. (2020) (see also Muchowska and Moran 2020).

I have written above the word "information". Nothing can be more dangerous. The word information is multisemic, like "richness", "democracy" or "beauty". Its meaning depends on the reader and on the context. It does not help much by saying that "information is energy", nor by saying that information theory is a highly developed science, starting from George Boole going all the way to AI. And it does not help quoting in passing that Claude Shannon obtained his PhD in Cold Spring Harbor Laboratory, the temple of American molecular biology, with a thesis on "An algebra for theoretical genetics".

In this Universe, everything is information. If our goal is to define life and to find the borders between the living and the nonliving, we need to mitigate this conundrum by focusing on a selected part of the problem. The information of the extant organisms on this planet encompasses, for instance, epigenetics and topology, which are emergent properties embedded in the linear information of our founding polymers. Epigenetics greedily multiplies genetic information and inscribes on DNA the history it goes through; supercoiling (a typically topological property) is a way to multiply and modulate information to regulate and direct genetic expression and replication; some molecules can handle it, some cannot. Are epigenetics and topology only part of thermodynamics, or are they elaborate and highly evolved properties of living entities? The answer by the layman scientist is as follows: both are emergent properties of living entities. Hence, life entails superposition of information levels, which is one of the keys of the evolutionary process.

The question, "how much in life can be considered an emergent property?" is thus justified. If we are trying to retrace the first steps of life, we need to have this question clear in mind.

Keeping the conservative approach of considering life only the ensemble of the structures and interactions of those phenomena that we know based on our terrestrial experience, the classes of molecules that are interesting for us here are the ones that we have under the eyes: DNA, RNA, proteins, carboxylic acids and aliphatic chains. These molecules are each endowed with their own characteristic properties and, at the same time, are functionally interconnnected. Their mutual connections give rise to cycles, conceived in that form of living topology that owns much to Eörs Szathmary (2000). In this perspective, life is the...