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- Herausgeber: tredition
- Kategorie: Religion und Spiritualität
- Sprache: Englisch
Life on earth arose through the creative interplay of prebiotic conditions on earth and the everlasting reliable macrocosmic changes of light and darkness. The first life molecules were confronted with the Earth's two-faced environment manifesting itself as a rhythm of a damaging light phase (day) and a harmless low light dark phase (night) produced by the apparent celestial movements within the earth-moon-sun system. It required two mutually complementing molecule types: ribonucleic acids and peptides, which had to adapt jointly to that fundamental duality in order to achieve a 'duration across change'. Both combined into a helically intertwined ribonucleopeptide filament as the initial molecular structure of life on earth. The predictable alternation of a damaging (UV irradiation, high-energy sun light) and a non-damaging (low-energy moon light) phase lead to the inclusion of rhythmic repair and timing in molecular life from begin on. The ribonucleopeptide filament responded to the dual qualities of its environment by behaving like an 'oscilloid'. Rhythmically alternating contraction to prevent damage during daytime and expansion to allow self-sustained repair during nighttime initiated the oscillation of the primordial biological timer as a molecular reflection of the macrocosmic time on Earth impacted by the light/dark rhythm. Macrocosmic time is both circular, because days, months and years consist of recurring cycles of light and darkness, and linear, because successive days, months and years are not identical repeats of the preceding ones and follow each other in a row. Corresponding to this yin/yang structure of macrocosmic time, biological time is also cyclical and linear at the same time. Under this perspective, life arose as an earth-bound molecular pattern instructed by celestial rhythms. Interestingly, there exists a correspondence to the dual, mutually complementing molecular basis of life in ancient Chinese mythology. A helically intertwined ribonuclopeptide filament represents an equivalent, a living reflection, of the T'ai chi symbol with its mutually complementing, inseparable black and white components that illustrate the fundamental duality of darkness and light or night and day on Earth. Yang and Yin, and Ch'ien and K'un, constitute the basic duality of the yin/yang philosophy and the ancient Chinese Book of Changes, the I Ging, respectively. Fu-hsi and Nü-kua, the personified versions of this basic duality, are characterised by their helically intertwining snake- or dragon-like lower bodies. Together, they are linking Earth to Heaven.
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Veröffentlichungsjahr: 2023
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Roland Frey
The origin of life is rhythmic repair
or
Macrocosmic rhythms created life
© 2024 Roland Frey
Verlag: tredition GmbH, Hamburg
ISBN
Softcover
978-3-347-88801-2
Hardcover
978-3-347-88803-6
E-Book
978-3-347-88806-7
Printed in Germany
All rights reserved. This publication may not be reproduced, in whole or in part, including illustrations, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the tredition publishing company and the author.
Dr. Roland Frey
Bütower Straße 22
12623 Berlin
The origin of life is rhythmic repair
The origin of life is rhythmic repair
or
Macrocosmic rhythms created life
To survive, complementary primordial life molecules had to become self-repairing timers oscillating in harmony with the macrocosmic environmental rhythms on Earth
Legend to the cover illustration
Rhythmic repair is the original organisation of life
Microcosmic ribonucleopeptides and macrocosmic rhythms are oscillating in harmony. The background design of this illustration derives from an ancient Chinese coin with a central quadratic hole, symbolising square earth, and a circular outer contour, symbolising round heaven. From begin on the primordial life molecules were sandwiched between the habitats available on the early Earth and the macrocosmic rhythms of light and dark mainly caused by the sun and the moon, and the Earth’s rotation. To achieve survival or a ‘duration across change’ the first mutually complementing ribonucleopeptide molecules inevitably had to fit the macrocosmic constellations prevailing on the early Earth, above all the rhythm of day and night symbolised by the yellow and grey half-circles, respectively. This basic yin/yang-like division of two inextricably linked and mutually complementing elements: non-damaging nocturnal darkness and damaging high-energy daylight, further subdivided into four parts the beginning of which is marked by dawn, midday, dusk, and midnight, respectively. Likely, the environmentally induced damage itself drove the primordial ribonucleopeptides to become an oscillating, self-repairing reflection of the macrocosmic rhythms on Earth. Later on, the endogenous anticipation of dawn and dusk and corresponding preparatory rhythmic compaction and decompaction, effected through changing from a closed to an open conformation, considerably reduced the amount of immediate damage. Only the coupling of basic life processes, primarily repair and replication to that diurnal, regularly alternating closing and opening of the ribonucleopeptide structure allowed the microcosmic primordial life molecules to oscillate in harmony with the macrocosmic rhythms on Earth and, thereby, to survive. Under this perspective, life arose as an earth-bound molecular pattern instructed by rhythmical celestial changes. In other words, time has been an integral part of life right from the outset.
This book is dedicated to
my deceased parents, Centa and Werner Kaffenberger,
Michelstadt im Odenwald,
to my late academic teacher in evolutionary biology and PhD supervisor
at Freiburg University, Germany, in the 1980ies,
Günther Osche, and
to late Walter Bock, formerly Columbia University New York, who, after
having read my PhD thesis, wrote a letter of support
without knowing me personally.
Mottos
In many of today's "leading" societies consumption has become the dominant aspect of individual lives. Used things are discarded and new things are bought instead. The consumer society opposes to the repair of things, preferring the new to anything old. This attitude causes short lifespans of produced items. Some have inbuilt failures that occur shortly after the warranty period has ended. In contrast, repair is a set of techniques that prolong the life of objects. Formerly, up to the second half of the 20th century approximately, a culture of repair, documented by thousands of repair shops (for shoes, clothing, domestic appliances, furniture etc) was found in many countries including, e.g., Germany and Russia. In Russia, this kind of repair culture has been termed 'remont' (peMOHT). In Estonia, in the old-town of Tallin, there is still (2017) an active, tiny remont business that has been on Nunne Street since 1920, and is the oldest of its kind in Estonia. Sort of a curiosity today, such residues of a culture of repair remind us of repair as a practice that establishes continuity, endurance, and sensitivity toward materials. Innovative repair often requires performing a large number of diverse tasks and making do with whatever is at hand. Therefore, it conforms to the concept of ‘bricolage’, the opportunistic rearrangement and recombination of existing elements. Frequently, a dedicated bricoleur accumulates an immense amount of things in a mostly small cabinet. If asked, why he keeps all these things, which to most people look like scrap and waste, the bricoleur would respond: "because I could need one of these pieces at some point in the future." Under this perspective, repair can be understood as an opportunistic process of change along a time scale and, thus, bears resemblance to the 'tinkering mode of evolution' as an inherent principle of evolutionary transformation. This insight could teach us a way to a sustainable future by restoring and renewing a culture of repair through remembering a time when things were fixed instead of being discarded (Jacob 1977; Benjamin 1999; Jordan 2006; Bock, G 2007; Laubichler 2007; Bock, WJ 2009; Gerasimova & Tchoukina 2009; Heckl 2013; Martínez 2017; Schultz 2017; Hanstein et al 2022).
"I keep thinking of the old Japanese practice of kintsugi or 'golden repair'. The idea behind this ancient ceramic art includes the sense that when something valuable cracks or breaks, it should be repaired carefully and lovingly in a way that adds to its value. Thus, the cracks and fault lines in a valuable bowl would be fitted with a laquer made of resin containing powdered gold. Such a golden repair does not try to cover up the cracks in the vessel or deny the fact of the matter. Rather, the cracks and splits and broken places become filled with gold. Beauty appears exactly where the worst faults previously existed and the golden scars add to the living story and to the value of the container" (Meade 2015).
In the context of this book, it appears as if we could learn a lot for our modern societies from the 'molecular repair culture' that has been an indispensable feature of life from the beginning and still is in guaranteeing life's ‘duration or continuity across change’.
Inhalt
Cover
Title Page
Copyright
Legend to the Cover Illustration
Dedication
Mottos
Prologue
Introduction
Uv Damage of Primordial Life Molecules & Viral Replication
Dual Prebiotic Molecular Scenario and Ancient Chinese Mythology
The Oscilloid Model
Self-Protection of Helical Nucleoprotein Filaments
Ring-Shaped Proteins and Nucleoprotein Filaments
Transcription and Replication of Helical Nucleoprotein Filaments
Repair and Recombination of Helical Nucleoprotein Filaments
The Sos Response of Bacteria
The General Stress Response of Bacteria
Rhythmic and Sequential Protein Phosphorylation
I) Circadian timing:
II) Nucleoprotein repair:
III) Inorganic polyphosphate:
Evolution of a Rhythmical Nucleoprotein Repair Mechanism
Transfer Rna (Trna) Evolution
Aminoacyl-Trna Synthetases
Ribosomes and Translation
Definition of Primordial Life on a Pre-Cellular, Molecular Level
Tumourigenesis or the Cancer Connection
The Ageing Connection
The Signalling Connection
One-component signalling:
Two-component signalling:
Similarity of two-component signalling and circadian clocks:
Biological Time
Synopsis - the Evolution of a Rhythmically Self-Repairing Timer
Final Remark
Epilogue
Acknowledgements
List of Illustrations
References
The origin of life is rhythmic repair or Macrocosmic rhythms created life
Cover
Title Page
Copyright
Legend to the Cover Illustration
Dedication
Prologue
Introduction
Epilogue
The origin of life is rhythmic repair or Macrocosmic rhythms created life
Cover
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Back Cover
Introduction
At the beginning of molecular life on Earth the primordial life molecules (the precursors of nucleic acids and proteins) were confronted with rhythmically occurring adverse environmental conditions. As a result of negligible atmospheric oxygen and lack of an ultraviolet (UV) absorbing ozone layer, the Earth's surface was bathed in UV light and hostile to life during daytime. Thus, strong light and UV radiation during the high-energy daylight phases periodically damaged the primordial life molecules whereas the low-energy night phases of the day did not interfere with the primordial life processes: self-protection, self-repair and self-replication (cf. Rothschild 1999; Schopf 1999; Bérces et al 2003; Gehring & Rosbash 2003; D'Antoni et al 2007; Powner et al 2009; Martin & Sousa 2016). As a consequence, this rhythmical environment (cf. Kuhn 1972, 1975, 1976; Kuhn & Waser 1981, 1982, 1983) forced the primordial life molecules to become rhythmically self-repairing molecular timers. This allowed them to oscillate in harmony with the environmental rhythms on Earth by protecting themselves as far as possible during the recurring damaging diurnal strong light phases and by shifting repair and replication to the interspersed harmless nocturnal low light phases. This separation of diurnal from nocturnal processes could have been enforced by sunlight-induced photo-oxidative stress as a selective pressure (cf. Bolige et al 2005b; Latifi et al 2008; Uchida et al 2010; Patke et al 2019; Kawasaki & Iwasaki 2020).
Essentially, the evolving primordial life molecules had to integrate the macrocosmic patterns of light and darkness on Earth in their own structure and functions, implying adaptation to the predictable temporal order of appearance of these environmental changes. Consistently, the natural temporal order of external stimuli is embedded in the wiring of the molecular regulatory network in Bacteria (Mitchell et al 2009). The molecular sensing of time, as one of the most important universal determinants, was entrained by the macrocosmic manifestation of time, the daily light/dark cycle and the changing light/dark ratio along the days of a year in non-equatorial regions, from begin on. It confers a considerable selective advantage to entrained and synchronised life forms in comparison with life forms not synchronised with the macrocosmic cyclical light/dark time structure (Dodd et al 2005; Ma et al 2013). A prominent benefit of circadian timing includes minimising nucleic acid and protein photo-damage by limiting repair and replication to nighttime (Johnson & Golden 1999; Cohen & Golden 2015; Gehring & Rosbash 2003; Foster & Kreitzman 2005, p. 156, 166f; 2009; Uchida et al 2010; Patke et al 2019).
How important this synchronisation with the environmental light/dark cycles is on an organismal level, can be inferred from the fact that, in mammals, an entrainable circadian clock is already present in the fetal brain (hypothalamic suprachiasmatic nuclei) and, beyond that, the fetuses in the uterus are informed about the phase of the environmental light/dark conditions. During fetal development, the mother acts as a transducer between the environment and the fetal brain suprachiasmatic nuclei, coordinating the phase of the developing circadian clock to her own clock time, which in turn, is entrained by ambient lighting and darkness. This form of materno-fetal communication appears to have evolved to prepare the developing mammal for entry into the external environment. As the neural mechanisms necessary for both the photic entrainment and overt expression of circadian rhythms mature, maternal coordination would ensure that the developing fetal endogenous rhythms are expressed in appropriate temporal relation to each other and to the 24-hour day. Without maternal coordination, the fetal endogenous circadian rhythms would develop uncoordinated until postnatal direct contact with environmental light/dark cycles acted to synchronise the phase of the neonate endogenous circadian rhythms. The circumnatal period of temporal disorganisation might render the already vulnerable neonate even more susceptible to various insults potentially decreasing survival (Reppert & Schwartz 1983).
Regarding primordial life molecules, the environmentally guided evolutionary acquisition of an inbuilt timer required the structural and functional combination of two contrasting but complementary primordial life molecule species: nucleic acids (likely oligoribonucleotides, then RNA) and nucleic acid (RNA)-binding proteins (oligopeptides in the beginning) (cf. Lahav & Nir 1997; Balcerak et al 2019). Otherwise, their survival or 'duration across change' would have been impossible. In other words, the basic function of life is adaptation to the uninterrupted alternating impact of two opposing features - light and darkness (cf. Fiedeler 1988, p. 168f.). Thus, life has been a reflection of this fundamental duality from begin on. The duality of the macrocosmic world on Earth was early recognised by ancient Chinese scholars and depicted in the well-known T’ai chi symbol (cf. Frey 2016 - Fig. 1).
Fig. 1: The T’ai chi symbol illustrates the fundamental duality of darkness and light or nighttime and daytime on Earth to which the mutually complementing primordial life molecules (primordial proteins and nucleic acids) had to adapt jointly in order to achieve a 'duration across change'.
The origin of the T’ai chi symbol lies in the graphical representation of the daily changes of a pole’s shadow length. This length varies for each day when measured at the same time of day. On the Northern hemisphere, long shadows coincide with a low sun and short days (long nights, winter) and short shadows with a high sun and long days (short nights, summer). Therefore, by measuring and plotting a pole’s shadow length over one year, ancient Chinese scholars received the daily changing ratio of darkness (night length) and light (daylight length) during one year. Additionally, this method allowed defining the length of a year to comprise about 365.25 days. The graphical representation of this approach provides the T’ai chi symbol (Figs. 1, 2). However, the graphic result depends on the geographical latitude of the observer’s location. Thus, computing the T’ai chi symbol for different latitudes yields different shapes of the black and white areas of the symbol. For this reason, the T’ai chi symbol given in Figs. 1 and 2 is just an average, oversimplified, rough approximation of many different possible shapes. Furthermore, the shape of the T’ai chi symbol depends on the ecliptic angle of the earth. The ecliptic determines the sun’s apparent path around the earth and this is why the ecliptic affects the yin and yang areas and the outer circle of the T’ai chi symbol. The ecliptic cyclically changes over the millennia between about 21°55’ and 24°18’. In the year 2000 it was about 23°26’19’’ while 3000 BC it was about 24°1.6’. Therefore, compared to the modern T’ai chi symbol the ancient T’ai chi symbol looks slightly different when derived by measuring a pole’s shadow length during one year. Consequently, due to the cyclical change of the earth’s ecliptic, any particular T’ai chi symbol is only a snapshot in time (Jaeger 2012; cf. Ji et al 2001; Fang 2015).
Both the daily changes of the ratio of darkness and light over one year and the relation to the earth’s cyclically changing ecliptic during several tens of millennia point to a connection of the T’ai chi symbol with time. Therefore, in addition to describing the two fundamental complementing cosmic features, the T’ai chi symbol involves a graphic description of time. The outer circle symbolises one year and the shape of the black and white areas describe the continuous daily changes of darkness and light along the annual cycle. The tiny Yang begins at the winter solstice amidst the maximal dominance of Yin and continually increases via the vernal equinox, where daytime and nighttime are equal, towards the summer solstice, where Yang reaches maximal dominance. Conversely, the tiny Yin begins at the summer solstice amidst the maximal dominance of Yang and continually increases via the autumnal equinox, where daytime and nighttime are equal, towards the winter solstice, where Yin reaches maximal dominance (Fig. 2). Or else, darkness is born at the longest day of summer, whereas light is born at the shortest day of winter. Thus, when Yin reaches its extreme, it becomes Yang; when Yang reaches its extreme, it becomes Yin. This is the significance of the white (yang) dot in the black (yin) area and of the black (yin) dot in the white (yang) area of the T’ai chi symbol. The seed of Yin is hidden in Yang, and the seed of Yang is hidden in Yin enabling the endless transitions between both. As Yin and Yang also represent the basis of the I Ging, the ancient Chinese ‘Book of Changes’, this book literally integrates the perennial rhythm of light and darkness via the unbroken (light, yang) and the broken line (darkness, yin) in its formal hexagram system. Both forces cannot exist without each other. It is the continuous dialectical interaction between Yin (moon) and Yang (sun) and the resulting continuous change of dark and light that define our world and produce the rhythm of life (Jaeger 2012; cf. Fiedeler 1988; Ji et al 2001; Fang 2015; Frey 2016). And here lies the connection to the evolution of life. Continuous change is also a fundamental principle of life. This change affected and guided the evolution of the primordial life molecules, which had to reflect the dual nature of their environment in their molecular structure and follow the macrocosmic rhythm of Yin and Yang by evolving a corresponding molecular microcosmic rhythm. Staying in harmony or synchrony with macrocosmic time on earth, emanating from the dynamic interaction of Yin and Yang, was the only way of surviving. Therefore, the basic principle of life is Yin and Yang.
Fig. 2: T’ai chi symbol with summer & winter solstice and vernal & autumnal equinoxes indicated. The origin of the T’ai chi symbol lies in the graphical representation of the daily changes of a sunlit pole’s shadow length. By measuring and plotting the shadow length over one year, ancient Chinese scholars received the daily changing ratio of darkness (night length) and light (daylight length) during one year. Additionally, this method allowed defining the length of a year to comprise about 365.25 days. The graphical representation of this approach provides the T’ai chi symbol. However, the graphic result depends on the geographical latitude of the observer’s location. Thus, computing the T’ai chi symbol for different latitudes yields different shapes of the black and white areas of the symbol. For this reason, the T’ai chi symbol given in Figs. 1 and 2 is just an average, oversimplified, rough approximation derived from many different possible shapes. (The illustration was created using Jaeger 2012.)
The macrocosmic rhythms of light and darkness are profound and predictable environmental changes. Therefore, we can expect corresponding adaptations of the primordial life molecules. Those macrocosmic rhythmical changes are calendaric (diurnal, mensual, annual) and, accordingly, the adaptive primordial molecular cycles should somehow reflect or be in harmony with the macrocosmic calendaric rhythms (cf. Frey 2016). In other words, at the base of life should stand simple molecular timers or microcosmic biological clocks that, somehow, were shaped by daytime and nighttime.
The cyclicity of those calendaric rhythms, arising from the apparent circular movements of the moon and the sun observed from the earth, is still contained in the words 'annual' (yearly), 'année' (year), deriving from Latin 'annulus' or French 'anneau' (ring) (Leuck 1977, p.11).
In addition, the primordial life molecules should be capable of repairing the damages inflicted on them during the destructive daylight hours in the course of the following night. Thus, from begin on primordial life molecules were subjected to enormous temporal constraints.
If the early Earth's rotation was faster than today, then the lengths of the day, month and year would have been correspondingly shorter: possibly only 20h, 15 h or even 4h at 3.5 billion years ago. The shorter day length would have provided more frequent but shorter periods for dark repair. Consequently, the necessary delays in an ancestral molecular circadian timer in order to match the environmental light/dark rhythm would have been shorter, too, and, therefore, easier to achieve on a molecular basis than with the 24 h day length of today. Hence, when reasonably assuming a shorter day length on early Earth, then the observable long delays of contemporary circadian clocks would have evolved over large time periods in the course of the Earth’s history, and were not yet in place at the time of life’s origin (Walker et al 1983; Walker & Zahnle 1986; Rothschild 1999; Tauber et al 2004; cf. Lakin-Thomas 2000; Hardin & Panda 2013; Frey 2016, p. 45).
The ancient metabolic cooperation between the precursors of ribonucleic acids (oligoribonucleotides) and proteins (oligopeptides) is suggested by the structure of ribonuclease-P, a ribozyme, which consists of two subunits, one of which is RNA and the other a protein. Surprisingly, it is the RNA of ribonuclease-P that exhibits catalytic activity and its catalytic efficiency is merely increased by the protein. This finding would suggest considering RNA as the primordial catalytic molecule of metabolism. In this perspective, ribonuclease-P would appear as a biochemical fossil, recapitulating an era, in which RNA functioned as the catalyst, whose stability was enhanced and its activity modulated by its accompanying protein (Szathmáry 1999).
Later, the protein component, possibly because of a greater potential for the generation of a variety of catalytic groups, might have taken over the catalytic function and the RNA was shed in all but a few cases. Perhaps, the greater structural variety of amino acids, compared with the nucleotides of RNA, allowed more elaborate catalytic properties in protein enzymes than in those composed of RNA (cf. Bernhardt 2012).
Catalysis by RNA is involved in self-splicing of the ribonucleic acid, i.e. in cutting itself into appropriate pieces; the reactions require an ester exchange between phosphate esters. Similar ester exchange is also of great importance in genetic recombination. The necessity for such an ester exchange provides an additional reason to prefer phosphate esters to proteins as molecules for genetic information (Westheimer 1986, 1987).
Apart from the macrocosmic rhythms of light and darkness, the primordial life molecules on the early Earth had to cope with a reducing, anoxic primary atmosphere, i.e. with a primordial atmosphere that, in contrast to the earth's present oxidizing atmosphere, did not contain appreciable amounts of oxygen (cf. Margulis et al 1976; Des Marais et al 1992; Knoll & Holland 1995; Canfield 2005; Holland 2006; Lunine 2006; Kump 2008; Shaw 2008; Blank & Sánchez-Baracaldo 2010; Nisbet & Fowler 2011; Mulkidjanian et al 2012; Martin & Sousa 2016; Xavier et al 2020). The Earth has been anaerobic throughout most of the history of life (Rothschild & Mancinelli 2001). After formation of the first solid land masses and cooling down to temperatures around 100°C, ubiquitous strong volcanic activities gave rise to the earth's secondary atmosphere containing CO2, N2, H2O, SO2, and, possibly, small amounts of O2. Hence, this secondary atmosphere was already less reducing than the earth's primary atmosphere although it contained very little if any amounts of oxygen. At nighttime, condensation of water from this secondary atmosphere was possible. Prevailing temperatures around the boiling point of water and alternating evaporation/condensation (wet/dry) cycles due to surface temperature fluctuations as a consequence of the day/night rhythm must have evoked vigorous atmospheric phenomena such as thunderstorms with frequent electrical discharges (lightnings). Under these conditions and the gas mixture of the secondary atmosphere, amino acids are readily produced as confirmed by experimental evidence. Organic products stemming from atmospheric gas phase reactions and soluble compounds present in the crust of the earth (e.g. mineral salts) dissolved in the increasing amounts of liquid water (Miller 1997; Rode 1999; Patel et al 2015).
The definite switch from an ancestral reducing towards a derived oxidising atmosphere occurred in the course of the earth's history and is thought to result from the evolution of living beings, e.g. in microbial mats and stromatolites, i.e. accretionary organosedimentary structures, commonly thinly layered, macroscopic and calcareous, produced by the activities of mat-building communities of mucilage-secreting micro-organisms, mainly filamentous photoautotrophic Prokarya such as Cyanobacteria (Schopf 1983, 1999, p.184; Walter 1983; Castenholz et al 1991; Lazcano & Miller 1994; Olson 2006; Mimuro et al 2008; Hörnlein et al 2018; cf. Whitman et al 1998; Gómez-Espinosa et al 2015). It should be noted that the groundbreaking biochemical processes involved in the formation of the primordial life molecules had been established during the Hadean and Archean aeons before the so-called 'great oxygenation event' at the beginning of the Proterozoic about 2.5 billion years ago, i.e. under a reducing atmosphere, and did not change substantially thereafter (cf. Dietrich et al 2006; Xavier et al 2020). In the course of the Proterozoic, the 'era of microorganisms' (Forchhammer 2014; cf. Schopf 1978) lasting for almost 2 billion years, the oxygen content of the atmosphere remained low and stagnated at about 3% (Berner 1999). Presumably, the separation into the three kingdoms of life, Bacteria, Archaea and Eukarya (Woese & Fox 1977; Woese et al 1987, 1990; Forterre 1997; Woese 1998; Wegener Parfrey et al 2011; Martin et al 2016) or, alternatively, into Bacteria and Archaea (Raymann et al 2015; Martin & Sousa 2016), occurred already during this period. A profound rise of the oxygen content of the atmosphere at the end of the Proterozoic about 0.54 billion years ago and the concomitant evolutionary burst of multicellular 'higher life forms', often termed 'Cambrian explosion' marks the transition to the Phanerozoic (cf. Kasting 2001; Forchhammer 2014). As a positive consequence of the long periods of an ancestral reducing atmosphere, somehow assembling primordial life molecules were not immediately destroyed by being oxidised (cf. Fridovich 1977). Accordingly, life, in contrast to most extant life forms, was not coupled to oxygen from begin on and initial respiration must have occurred anaerobically, i.e. without oxygen. In other words, early life was the age of anaerobes (cf. Decker et al 1970; Canfield 2005; Dietrich et al 2006; Fuchs 2011; Martin & Sousa 2016; Sousa et al 2016). Consistently, a reconstruction of the core reactions of an ancient autotrophic metabolism suggested its origin in a highly reducing, potentially aqueous or rhythmically alternating aqueous/terrestrial, environments resulting from wet/dry cycles. The reducing character is revealed by the abundance of redox reactions in the autotrophic core, the central role of CO2, and the circumstance that the core metabolism's main products (amino acids and nucleic acids) are far more reduced than CO2 (Sousa et al 2016; Xavier et al 2020; Wimmer et al 2021b). Likewise, any initial metabolism in an atmosphere that did not contain oxygen must have occurred as some sort of fermentation.
Under such anaerobic conditions, oxidising and reducing reactions consist in the transfer of electrons, oxidation being the loss of electrons and reduction the gain of electrons. One of the reaction partners is oxidised while the other is simultaneously reduced. Therefore, these reactions are called redox reactions (Fig. 3). Most life on Earth is based upon such redox chemistry and it was redox reactions that transformed the earth's atmosphere (cf. Martin & Russell 2003; Allen et al 2008; Forchhammer 2014; Lyons et al 2014; Xavier et al 2020).
Oxidation and reduction, very much as light and darkness or daytime and nighttime, are unseparably coupled, one cannot occur without the other. Consequently, this basic duality of chemical reactions that do not necessarily include oxygen (!) can be illustrated by adapting the dynamic coupling of redox functions to the T’ai chi symbol, 'plus' (+) representing reduction and 'minus' (-) representing oxidation (Fig. 3).
Fig. 3: Modified T’ai chi icon to symbolise the unseparable coupling of reduction and oxidation as so-called redox reactions. In analogy to the complementarity of light and darkness or daytime and nighttime, illustrated by the original T’ai chi symbol (cf. Figs. 1, 2), the modified T’ai chi icon denotes the gain of electrons (+) by the blue component complementary to the simultaneous loss of electrons (-) by the red component.
The electrons involved in redox reactions move along an energy gradient between the electron donator and the electron acceptor and, accordingly, this gradient is called a redox potential. The higher the redox potential between an electron donator and an electron acceptor the higher is the difference in free energy between the redox partners (Czihak et al 1976; Morowitz et al 2000).
Presumably, the energy required for the assembly and maintenance of the primordial life molecules was derived from such kind of redox potentials. This implies that redox reactions, even before substantial amounts of oxygen had accumulated in the atmosphere in the Great Oxidation Event ≈ 2.5 billion years ago (Dietrich et al 2006; Goldblatt et al 2006; Edgar et al 2012; Lyons et al 2014; Martin & Sousa 2016; Xavier et al 2020), represent an innate precondition of life and accompanied life on Earth from begin on.
Therefore, it is of note that chemoautotrophic Bacteria and Archaea can use the energy stored in several inorganic substrates, e.g. hydrogen sulfide (H2S), elemental sulfur (S), ferrous iron (Fe2+), manganese (Mn2+), molecular hydrogen (H2), ammonia (NH4+), to build up organic molecules from carbon dioxide and water. This so-called chemosynthesis involves redox reactions in the course of which the inorganic substrates are used as electron donators, thereby becoming oxidised whereas the reduction of carbon dioxide, nitrogen compounds and water are used to generate life-supporting molecules. This implies that chemolithoautotrophic metabolism preceded heterotrophic and photoautotrophic metabolisms (cf. Wheelis 1984; Keller et al 1994; Nisbet et al 1995; Pace 1997; Morowitz et al 2000; Martin & Russell 2003; Ferry & House 2006; Hansel & Francis 2006; Nakagawa & Takai 2008; Nisbet & Fowler 2011; Mulkidjanian et al 2012; Sousa et al 2016; Ranjan et al 2018, 2019; Xavier et al 2020).
Aerobic metabolism is far more efficient than anaerobic but the exploitation of oxygen-involving reactions has its costs (Ljungman & Hanawalt 1992). Oxidative damage resulting from the reduced forms of molecular oxygen, especially the hydroxyl radical, is extremely serious; therefore, reactive oxygen species (ROS) represent a pervasive threat. ROS include singlet oxygen (1O2), superoxide (O2-), hydrogen peroxide (H2O2) and hydroxyl radicals (*HO). Externally, hydroxyl radicals are produced by ionising radiation, and H2O2 arises photochemically from UV radiation. Internally, ROS are generated during aerobic metabolism (Szibor et al 2001; Murphy 2009; Shokolenko et al 2009) and photosynthesis (Oh & Kaplan 2000). In general, excess ROS levels are toxic to the cell. If more H2O2 is produced than catabolised, the ROS will result in cellular damage or even cell death (Hockberger et al 1999). However, ROS are also used in redox signalling, in which ROS, e.g. H2O2, function as signalling molecules via chemoselective oxidation of cysteine residues in proteins (cf. Wilson & González-Billaut 2015). Therefore, a balance in cellular ROS is important for cell development and physiology. The amino acid cysteine can exist in a number of oxidation states. Such reversible cysteine modifications can constitute a facile switch for modulating protein function akin to phosphorylation. Notably, the presence of oxygen can enhance radiation-induced DNA damage (Rothschild & Mancinelli 2001; D'Autreaux & Toledano 2007; Paulsen & Carroll 2010; Yoshida et al 2011).
The connection between the dark/light complementarity and the reduction/oxidation complementarity, i.e. between the cyclic mutual relationships symbolised in Figs. 1, 2 and 3, in today-living cellular organisms arises from the production of H2O2 and other so-called reactive oxygen species (ROS) under the influence of UV irradiation and energy-rich, short-wave visible light. Intracellular levels of H2O2 are modulated by peroxiredoxins, a family of antioxidant proteins. Cycles of oxidation and reduction are conserved across all domains of life and, apparently, these cycles of redox reactions persist in the absence of the classical circadian transcription-translation feedback loops. Put another way, redox oscillations may represent a non-transcriptional, metabolic circadian timer that interacts and work in parallel with the canonical genetic mechanisms of keeping circadian time. Likely, however, a circadian timer based on redox oscillations and involving ROS could not evolve before the accumulation of atmospheric oxygen. Following this rationale, circadian oscillations of peroxiredoxin proteins are secondary adaptations that evolved much later than the canonical genetic mechanisms of circadian timekeeping. As light induces the production of H2O2, hydrogen peroxide may additionally act as a signal transducer relaying information about the light environment to the genetic circadian pacemaker (cf. Neill et al 2002; Hirayama et al 2007a; Paulsen & Carroll 2010; O’Neill & Reddy 2011; Edgar et al 2012; Lyons et al 2014; Cornish-Bowden 2015; Sousa et al 2016; Yoshida et al 2011; Wulund & Reddy 2015; Hörnlein et al 2018; Xavier et al 2020).
In modern organisms, light-induced ROS cause multiple deleterious effects to organic molecules including mutations and DNA damage. The production process is initiated by photoreduction of Flavin-containing oxidases, which absorb throughout the UVA-to-blue range part of the spectrum. These oxidases are versatile flavo-proteins that catalyse oxygenation in a large number of metabolic pathways, generating H2O2 as a by-product. Flavins (FAD and FMN) and flavoproteins are reduced and H2O2 is produced. Catalase proteins can metabolise H2O2 to H2O and O2 (Hockberger et al 1999; Kim & Miura 2004; Hirayama et al 2007a; cf. Herrmann et al 2008).
Catalase proteins are also important in plant metabolism in response to oxidative stress, and in signal transduction. Two Arabidopsis catalases, CAT2 and CAT3, are regulated by the circadian clock. The peak of CAT2 mRNA abundance is gated to subjective early morning (dawn), whereas the peak of CAT3 mRNA abundance is gated to subjective evening (dusk). The transcription of a third catalase, CAT1, is not clock-regulated. Both CAT2 and CAT3 are assumed to localise to the peroxisome. The different circadian phasing of their mRNA abundance suggest different metabolic roles of CAT2 and CAT3. The morning-specific expression of CAT2 is consistent with a role in the peroxisomal degradation of photorespiratory H2O2 during daylight hours. In contrast, the evening-specific expression of CAT3 points to a catalase required for H2O2 scavenging at night (Zhong et al 1994; Zhong & McClung 1996).
Interestingly, there exists a link between H2O2 signalling and the circadian clock in zebrafish light-responsive tissues. The cellular redox state is regulated by a critical balance between the production and degradation of H2O2 required for the light-dependent regulation of clock gene transcription. Apparently, flavin-containing oxidases that absorb light in the violet-blue region act as photoreceptors and induce photoreduction of FAD (Flavin Adenin Dinucleotide), leading to H2O2 production and clock gene transcription via a positive feedback loop. It is antagonised by an also light-induced increase of intracellular catalase activity after maximum expression of clock genes representing the negative feedback loop. Consequently, the light-dependent balance between H2O2 production and degradation, i.e. the cellular redox state, constitutes a signalling pathway that couples photoreception to the circadian clock in zebrafish.
Consistently, a key feature of ROS signalling pathways in Prokarya is feedback regulation. Beyond that, the transcription factor SoxR is a sensor of the superoxide anion (O2-). Oxidation of the SoxR [2Fe-2S] cluster by O2- causes a change of SoxR conformation that alters the structure of the SoxR-bound DNA operator, resulting in gene activation (D'Autreaux & Toledano 2007). Hence, two major features of a circadian clock, gene activation and feedback regulation, also occur in the ROS signalling pathways of Prokarya.
Rhythms in clock gene expression in zebrafish appear to be directly entrained by light. Moreover, photoreception is decentralised in zebrafish, i.e. cells, tissues and organs contain photoreceptors capable of sensing and transmitting light signals. In other words, multiple peripheral oscillators are directly set by light/dark cycles. Possibly, peripheral tissue photoreception occurs in many small, relatively transparent organisms, where light can penetrate deep into the body. In contrast, H2O2 is not able to trigger circadian oscillation in mammalian cells, presumably because peripheral tissues of mammals are not translucent and, thus, not light responsive (Whitmore et al 1998, 2000; Hirayama et al 2007a; cf. Foster & Kreitzman 2005, p. 129; cf. Uchida et al 2010).
However, even in mammals, in which, along the canonical pathway, light synchronises the SCN clock in the hypothalamus, and the SCN clock in turn transmits the timing information to peripheral clocks, there exist additional pathways that bypass the SCN clock and synchronise peripheral clocks independently of the SCN clock. Potentially, these additional pathways gain photic information from retinal input via various hypothalamic and some extra-hypothalamic regions outside the SCN and then induce endocrine, autonomic, or behavioural outputs that regulate peripheral clocks. This additional regulation might sustain synchronisation of multiple peripheral clocks through rhythmically released hormones such as melatonin (cf. Reiter 1991) or glucocorticoids, other blood-borne signals, or even body temperature cycles. Consequently, aside the strictly hierarchical SCN masterclock pathway there appears to exist a “federated” multi-clock circadian timing system. Redundant synchronisation pathways protect the circadian timing system from unwanted phase shifts in response to stochastic, conflicting or noisy zeitgeber signalling and allow for more differentiated responses and high-amplitude and robust circadian clock rhythmicity. Therefore, in a natural, rather noisy zeitgeber environment the multimodality of an SCN master clock plus independently regulated peripheral clocks seems to be advantageous for maintaining the circadian system’s temporal stability and plasticity (Troein et al 2009; Zhang & Kay 2010). According to experimental evidence, a shift of the feeding regimen caused a slow response in animals with an intact SCN but a rapid phase shift of the liver clock in animals after removal of the SCN. It appears, therefore, that a functional SCN pacemaker shields from peripherally induced rapid phase shifts and coordinates and maintains peripheral rhythmicity even in the absence of an external zeitgeber. In contrast, a “federated” circadian network allows for each clock, i.e. each physiological process, to be synchronised to those zeitgeber signals most relevant for a particular process, resulting in a tailored response. A network organisation might also facilitate seasonal adaptations of circadian rhythms by differential resetting of peripheral tissue clocks in response to changes in photoperiod, temperature, humidity and other parameters that change over the course of a year (Moore et al 1976; Liu Y et al 1998; Schaffer et al 1998; Messager et al 1999; Park et al 1999; Brainard et al 2001; Goldman 2001; Yanovsky & Kay 2002; Mockler et al 2003; Yoshimura et al 2003; Stoleru et al 2007; Zhang & Kay 2010; Husse et al 2015).
Coming back to primordial life molecules: from the outset, they were under enormous temporal constraint to oscillate in harmony with the ubiquitous alternation of light and darkness on earth. This required the integration of the macrocosmic rhythmical pattern in their microcosmic structure and becoming rhythmically self-repairing timers. Above all, the primordial mutually complementing life molecules had to adapt jointly to the rhythmically recurring photooxidative damage of sunlight, primarily caused by UV and high-energy short-wave visible light.
UV damage of primordial life molecules & viral replication
At a very early phase of molecular evolution of life, the strong daylight from the sun was too damaging for the primordial complementary life molecules, the precursors of proteins and nucleic acids. They were likely exposed to strong daylight, including high-energy visible violet and blue-light (400-500 nm) and intense ultraviolet (UV) irradiation as the Earth had not yet evolved a stratospheric ozone layer. UV radiation ranges from 1 to 400 nm, visible light from 400 to 750 nm and infrared from 750 nm to 2.5 µm. The ranges for UVC, UVB and UVA are: 1-280, 280-315, 315-400 nm, respectively. The peak absorption of DNA is at 260 nm and that of proteins at 280 nm on average. The stratospheric ozone layer of today strongly attenuates UVC and part of UVB wavelengths. For geologic times before such an ozone layer had accumulated, intense direct damage to the primordial ribonucleoprotein complexes by UV wavelengths and high-energy short wavelengths of visible light must have occurred.
However, even in the absence of an ozone shield, ZnS and MnS crystals efficiently scavenge UV up to approximately 320 nm. The molar absorption coefficient of ZnS particles is about 2mMcm-1 at 260 nm, corresponding to the absorption of nucleotides. Therefore, a 5µm-thin layer of ZnS would attenuate UV irradiation by a factor of 1010. Conservatively assuming a 90% porosity of ZnS-containing sediments and a 1% ZnS content in the sediments, a 5-mm layer of ZnS-containing precipitate would provide the same UV protection as a water column greater than 100m.
Similarly, clay minerals on early Earth, e.g. montmorillonite, could have shielded primordial life molecules, such as hairpin RNAs and oligopeptides, from UV damage and massive UV-driven degradation. Experimental evidence suggests a direct involvement of montmorillonite in preventing UV-induced structural rearrangements and function loss of RNA hairpins. Moreover, montmorillonite is known to catalyse the oligomerisation of mononucleosides into ≈ 50 nucleotide long RNA molecules (Ferris & Ertem 1992; Ertem 2004; Ferris 2006; Ertem et al 2008; Aldersley et al 2011; Jheeta & Joshi 2014; Mutsuro-Aoki et al 2020).
Remarkably, oligopeptides, like short RNAs (oligoribonucleotides), can also assume a hairpin conformation, e.g. ATP synthase (Girvin & Fillingame 1994; Fillingame et al 1998; Dautant et al 2010; Okuno et al 2011; Hahn et al 2018; Kondo et al 2021; Akiyama et al 2023; cf. Stock et al 1999; Mulkidjanian et al 2007).
Consequently, prior to formation of an ozone shield, local patches of inorganic UV protection may have existed on early Earth and functioned as UV shields for primordial life molecules, thereby promoting evolution towards more complex molecular organisation (Paietta 1982; Cockell 1998a,b; Rothschild 1999; Cockell 2000; Cockell & Horneck 2001; Bérces et al 2003; Chinnapen & Sen 2004; Westall et al 2006; Biondi et al 2007; Cnossen et al 2007; D'Antoni et al 2007; Powner et al 2009; Grenfell et al 2010; Mulkidjanian et al 2012; Jones & Baxter 2017; cf. Blankenship 1992; Slade & Radman 2011).
