The RNA world hypothesis on the origin of life is generally considered as the key to solve the “chicken and egg dilemma” concerning the evolution of genes and proteins as observed in the modern organisms. This hypothesis, however, contains several serious weak points. We have a counterproposal called [GADV]-protein world hypothesis, abbreviated as GADV hypothesis, in which we have suggested that life originated from a [GADV]-protein world, which comprised proteins composed of four amino acids: Gly [G], Ala [A], Asp [D], and Val [V]. A new concept “pseudo-replication” is crucial for the description of the emergence of life. The new hypothesis not only plausibly explains how life originated from the initial chaotic protein world, but also how genes, genetic code, and proteins co-evolved.
GADV hypothesis; pseudo-replication; [GADV]-protein world; origin of life
The RNA world hypothesis, that RNA genomes and catalysts preceded DNA genomes and genetically-encoded protein catalysts, has been central to models for the early evolution of life on Earth. A key part of such models is continuity between the earliest stages in the evolution of life and the RNA repertoires of extant lineages. Some assessments seem consistent with a diverse RNA world, yet direct continuity between modern RNAs and an RNA world has not been demonstrated for the majority of RNA families, and, anecdotally, many RNA functions appear restricted in their distribution. Despite much discussion of the possible antiquity of RNA families, no systematic analyses of RNA family distribution have been performed. To chart the broad evolutionary history of known RNA families, we performed comparative genomic analysis of over 3 million RNA annotations spanning 1446 families from the Rfam 10 database. We report that 99% of known RNA families are restricted to a single domain of life, revealing discrete repertoires for each domain. For the 1% of RNA families/clans present in more than one domain, over half show evidence of horizontal gene transfer (HGT), and the rest show a vertical trace, indicating the presence of a complex protein synthesis machinery in the Last Universal Common Ancestor (LUCA) and consistent with the evolutionary history of the most ancient protein-coding genes. However, with limited interdomain transfer and few RNA families exhibiting demonstrable antiquity as predicted under RNA world continuity, our results indicate that the majority of modern cellular RNA repertoires have primarily evolved in a domain-specific manner.
In cells, DNA carries recipes for making proteins, and proteins perform chemical reactions, including replication of DNA. This interdependency raises questions for early evolution, since one molecule seemingly cannot exist without the other. A resolution to this problem is the RNA world, where RNA is postulated to have been both genetic material and primary catalyst. While artificially selected catalytic RNAs strengthen the chemical plausibility of an RNA world, a biological prediction is that some RNAs should date back to this period. In this study, we ask to what degree RNAs in extant organisms trace back to the common ancestor of cellular life. Using the Rfam RNA families database, we systematically screened genomes spanning the three domains of life (Archaea, Bacteria, Eukarya) for RNA genes, and examined how far back in evolution known RNA families can be traced. We find that 99% of RNA families are restricted to a single domain. Limited conservation within domains implies ongoing emergence of RNA functions during evolution. Of the remaining 1%, half show evidence of horizontal transfer (movement of genes between organisms), and half show an evolutionary history consistent with an RNA world. The oldest RNAs are primarily associated with protein synthesis and export.
Recent developments in cosmology radically change the conception of the universe as well as the very notions of "probable" and "possible". The model of eternal inflation implies that all macroscopic histories permitted by laws of physics are repeated an infinite number of times in the infinite multiverse. In contrast to the traditional cosmological models of a single, finite universe, this worldview provides for the origin of an infinite number of complex systems by chance, even as the probability of complexity emerging in any given region of the multiverse is extremely low. This change in perspective has profound implications for the history of any phenomenon, and life on earth cannot be an exception.
Origin of life is a chicken and egg problem: for biological evolution that is governed, primarily, by natural selection, to take off, efficient systems for replication and translation are required, but even barebones cores of these systems appear to be products of extensive selection. The currently favored (partial) solution is an RNA world without proteins in which replication is catalyzed by ribozymes and which serves as the cradle for the translation system. However, the RNA world faces its own hard problems as ribozyme-catalyzed RNA replication remains a hypothesis and the selective pressures behind the origin of translation remain mysterious. Eternal inflation offers a viable alternative that is untenable in a finite universe, i.e., that a coupled system of translation and replication emerged by chance, and became the breakthrough stage from which biological evolution, centered around Darwinian selection, took off. A corollary of this hypothesis is that an RNA world, as a diverse population of replicating RNA molecules, might have never existed. In this model, the stage for Darwinian selection is set by anthropic selection of complex systems that rarely but inevitably emerge by chance in the infinite universe (multiverse).
The plausibility of different models for the origin of life on earth directly depends on the adopted cosmological scenario. In an infinite universe (multiverse), emergence of highly complex systems by chance is inevitable. Therefore, under this cosmology, an entity as complex as a coupled translation-replication system should be considered a viable breakthrough stage for the onset of biological evolution.
This article was reviewed by Eric Bapteste, David Krakauer, Sergei Maslov, and Itai Yanai.
It is now widely accepted that at an early stage in the evolution of life an RNA world arose, in which RNAs both served as the genetic material and catalyzed diverse biochemical reactions. Then, proteins have gradually replaced RNAs because of their superior catalytic properties in catalysis over time. Therefore, it is important to investigate how primitive functional proteins emerged from RNA world, which can shed light on the evolutionary pathway of life from RNA world to the modern world. In this work, we proposed that the emergence of most primitive functional proteins are assisted by the early primitive nucleotide cofactors, while only a minority are induced directly by RNAs based on the analysis of RNA-protein complexes. Furthermore, the present findings have significant implication for exploring the composition of primitive RNA, i.e., adenine base as principal building blocks.
Within eukaryotes there is a complex cascade of RNA-based macromolecules that process other RNA molecules, especially mRNA, tRNA and rRNA. An example is RNase MRP processing ribosomal RNA (rRNA) in ribosome biogenesis. One hypothesis is that this complexity was present early in eukaryotic evolution; an alternative is that an initial simpler network later gained complexity by gene duplication in lineages that led to animals, fungi and plants. Recently there has been a rapid increase in support for the complexity-early theory because the vast majority of these RNA-processing reactions are found throughout eukaryotes, and thus were likely to be present in the last common ancestor of living eukaryotes, herein called the Eukaryotic Ancestor.
We present an overview of the RNA processing cascade in the Eukaryotic Ancestor and investigate in particular, RNase MRP which was previously thought to have evolved later in eukaryotes due to its apparent limited distribution in fungi and animals and plants. Recent publications, as well as our own genomic searches, find previously unknown RNase MRP RNAs, indicating that RNase MRP has a wide distribution in eukaryotes. Combining secondary structure and promoter region analysis of RNAs for RNase MRP, along with analysis of the target substrate (rRNA), allows us to discuss this distribution in the light of eukaryotic evolution.
We conclude that RNase MRP can now be placed in the RNA-processing cascade of the Eukaryotic Ancestor, highlighting the complexity of RNA-processing in early eukaryotes. Promoter analyses of MRP-RNA suggest that regulation of the critical processes of rRNA cleavage can vary, showing that even these key cellular processes (for which we expect high conservation) show some species-specific variability. We present our consensus MRP-RNA secondary structure as a useful model for further searches.
During protein synthesis, tRNA serves as the intermediary between cognate amino acids and their corresponding RNA trinucleotide codons. Aminoacyl-tRNA is also a biosynthetic precursor and amino acid donor for other macromolecules. AA-tRNAs allow transformations of acidic amino acids into their amide-containing counterparts, and seryl-tRNASer donates serine for antibiotic synthesis. Aminoacyl-tRNA is also used to cross-link peptidoglycan, to lysinylate the lipid bilayer, and to allow proteolytic turnover via the N-end rule. These alternative functions may signal the use of RNA in early evolution as both a biological scaffold and a catalyst to achieve a wide variety of chemical transformations.
AA-tRNA; amino acid biosynthesis; Peptidoglycan synthesis; Membrane modification; Antibiotic synthesis
The RNA world hypothesis posits that the earliest genetic system consisted of informational RNA molecules that directed the synthesis of modestly functional RNA molecules. Further evidence suggests that it was within this RNA-based genetic system that life developed the ability to synthesize proteins by translating genetic code. Here we investigate the early development of the translation system through an evolutionary survey of protein architectures associated with modern translation.
Our analysis reveals a structural expansion of translation proteins immediately following the RNA world and well before the establishment of the DNA genome. Subsequent functional annotation shows that representatives of the ten most ancestral protein architectures are responsible for all of the core protein functions found in modern translation.
We propose that this early robust translation system evolved by virtue of a positive feedback cycle in which the system was able to create increasingly complex proteins to further enhance its own function.
This article was reviewed by Janet Siefert, George Fox, and Antonio Lazcano (nominated by Laura Landweber)
A little-noted result of the confirmation of multiple premises of the RNA-world hypothesis is that we now know something about the dawn organisms that followed the origin of life, perhaps over 4 billion years ago. We are therefore in an improved position to reason about the biota just before RNA times, during the era of the first replicators, the first Darwinian creatures on Earth. An RNA congener still prominent in modern biology is a plausible descendent of these first replicators.
Nucleotide cofactors such as NADP could represent relics of pre-RNA life on Earth. They may have been key elements of the first replicators, subsequently co-opted by RNA and then proteins.
Top-down causation has been implicit in many sociological accounts of social structure and its influence on social events, but the social sciences have struggled to provide a coherent account of top-down causation itself. This paper summarizes a critical realist view of causation and emergence, shows how it supports a plausible account of top-down causation and then applies this account to the social world. The argument is illustrated by an examination of the concept of a norm circle, a kind of social entity that, it is argued, is causally responsible for the influence of normative social institutions. Nevertheless, social entities are structured rather differently from ordinary material ones, with the result that the compositional level structure of reality implicit in the concept of top-down causation has some limitations in the social world. The paper closes by considering what might be involved in examining how top-down causation can be shown to be at work in the social domain.
downward causation; emergence; norm circles; social ontology; social structure
The RNA world hypothesis states that the early evolution of life went through a stage in which RNA served both as genome and as catalyst. The central catalyst in an RNA world organism would have been a ribozyme that catalyzed RNA polymerization to facilitate self-replication. An RNA polymerase ribozyme was developed previously in the lab but it is not efficient enough for self-replication. The factor that limits its polymerization efficiency is its weak sequence-independent binding of the primer/template substrate. Here we tested whether RNA polymerization could be improved by a cationic arginine cofactor, to improve the interaction with the substrate. In an RNA world, amino acid-nucleic acid conjugates could have facilitated the emergence of the translation apparatus and the transition to an RNP world. We chose the amino acid arginine for our study because this is the amino acid most adept to interact with RNA. An arginine cofactor was positioned at ten different sites on the ribozyme, using conjugates of arginine with short DNA or RNA oligonucleotides. However, polymerization efficiency was not increased in any of the ten positions. In five of the ten positions the arginine reduced or modulated polymerization efficiency, which gives insight into the substrate-binding site on the ribozyme. These results suggest that the existing polymerase ribozyme is not well suited to using an arginine cofactor.
The evolutionary puzzle of cooperation describes situations where cooperators provide a fitness benefit to other individuals at some cost to themselves. Under Darwinian selection, the evolution of cooperation is a conundrum, whereas non-cooperation (or defection) is not. In the absence of supporting mechanisms, cooperators perform poorly and decrease in abundance. Evolutionary game theory provides a powerful mathematical framework to address the problem of cooperation using the prisoner’s dilemma. One well-studied possibility to maintain cooperation is to consider structured populations, where each individual interacts only with a limited subset of the population. This enables cooperators to form clusters such that they are more likely to interact with other cooperators instead of being exploited by defectors. Here we present a detailed analysis of how a few cooperators invade and expand in a world of defectors. If the invasion succeeds, the expansion process takes place in two stages: first, cooperators and defectors quickly establish a local equilibrium and then they uniformly expand in space. The second stage provides good estimates for the global equilibrium frequencies of cooperators and defectors. Under hospitable conditions, cooperators typically form a single, ever growing cluster interspersed with specks of defectors, whereas under more hostile conditions, cooperators form isolated, compact clusters that minimize exploitation by defectors. We provide the first quantitative assessment of the way cooperators arrange in space during invasion and find that the macroscopic properties and the emerging spatial patterns reveal information about the characteristics of the underlying microscopic interactions.
evolutionary game theory; cooperation; spatial games; prisoner’s dilemma; invasion
A variety of macromolecules and small molecules—(oligo)nucleotides, proteins, lipids and metabolites—are collectively considered essential to early life. However, previous schemes for the origin of life—e.g. the ‘RNA world’ hypothesis—have tended to assume the initial emergence of life based on one such molecular class followed by the sequential addition of the others, rather than the emergence of life based on a mixture of all the classes of molecules. This view is in part due to the perceived implausibility of multi-component reaction chemistry producing such a mixture. The concept of systems chemistry challenges such preconceptions by suggesting the possibility of molecular synergism in complex mixtures. If a systems chemistry method to make mixtures of all the classes of molecules considered essential for early life were to be discovered, the significant conceptual difficulties associated with pure RNA, protein, lipid or metabolism ‘worlds’ would be alleviated. Knowledge of the geochemical conditions conducive to the chemical origins of life is crucial, but cannot be inferred from a planetary sciences approach alone. Instead, insights from the organic reactivity of analytically accessible chemical subsystems can inform the search for the relevant geochemical conditions. If the common set of conditions under which these subsystems work productively, and compatibly, matches plausible geochemistry, an origins of life scenario can be inferred. Using chemical clues from multiple subsystems in this way is akin to triangulation, and constitutes a novel approach to discover the circumstances surrounding the transition from chemistry to biology. Here, we exemplify this strategy by finding common conditions under which chemical subsystems generate nucleotides and lipids in a compatible and potentially synergistic way. The conditions hint at a post-meteoritic impact origin of life scenario.
prebiotic chemistry; systems chemistry; chemoselectivity; phosphorylation
According to the “thermodynamic hypothesis”, the sequence of a biological macromolecule defines its folded, active structure as a global energy minimum on the folding landscape.1,2 But the enormous complexity of folding landscapes of large macromolecules raises a question: Is there indeed a unique global energy minimum corresponding to a unique native conformation, or are there deep local minima corresponding to alternative active conformations?3 Folding of many proteins is well described by two-state models, leading to highly simplified representations of protein folding landscapes with a single native conformation.4,5 Nevertheless, accumulating experimental evidence suggests a more complex topology of folding landscapes with multiple active conformations that can take seconds or longer to interconvert.6,7,8 Here we employ single molecule experiments to demonstrate that an RNA enzyme folds into multiple distinct native states that interconvert much slower than the time scale of catalysis. These data demonstrate that the severe ruggedness of RNA folding landscapes extends into conformational space occupied by native conformations.
Ribonuclease P is an ancient endonuclease that cleaves precursor tRNA and generally consists of a catalytic RNA subunit (RPR) and one or more proteins (RPPs). It represents an important macromolecular complex and model system that is universally distributed in life. Its putative origins have inspired fundamental hypotheses, including the proposal of an ancient RNA world.
To study the evolution of this complex, we constructed rooted phylogenetic trees of RPR molecules and substructures and estimated RPP age using a cladistic method that embeds structure directly into phylogenetic analysis. The general approach was used previously to study the evolution of tRNA, SINE RNA and 5S rRNA, the origins of metabolism, and the evolution and complexity of the protein world, and revealed here remarkable evolutionary patterns. Trees of molecules uncovered the tripartite nature of life and the early origin of archaeal RPRs. Trees of substructures showed molecules originated in stem P12 and were accessorized with a catalytic P1-P4 core structure before the first substructure was lost in Archaea. This core currently interacts with RPPs and ancient segments of the tRNA molecule. Finally, a census of protein domain structure in hundreds of genomes established RPPs appeared after the rise of metabolic enzymes at the onset of the protein world.
The study provides a detailed account of the history and early diversification of a fundamental ribonucleoprotein and offers further evidence in support of the existence of a tripartite organismal world that originated by the segregation of archaeal lineages from an ancient community of primordial organisms.
The simplest conceivable example of evolving systems is RNA molecules that can replicate themselves. Since replication produces a new RNA strand complementary to a template, all templates would eventually become double-stranded and, hence, become unavailable for replication. Thus the problem of how to separate the two strands is considered a major issue for the early evolution of self-replicating RNA. One biologically plausible way to copy a double-stranded RNA is to displace a preexisting strand by a newly synthesized strand. Such copying can in principle be initiated from either the (+) or (-) strand of a double-stranded RNA. Assuming that only one of them, say (+), can act as replicase when single-stranded, strand displacement produces a new replicase if the (-) strand is the template. If, however, the (+) strand is the template, it produces a new template (but no replicase). Modern transcription exhibits extreme strand preference wherein anti-sense strands are always the template. Likewise, replication by strand displacement seems optimal if it also exhibits extreme strand preference wherein (-) strands are always the template, favoring replicase production. Here we investigate whether such strand preference can evolve in a simple RNA replicator system with strand displacement.
We first studied a simple mathematical model of the replicator dynamics. Our results indicated that if the system is well-mixed, there is no selective force acting upon strand preference per se. Next, we studied an individual-based simulation model to investigate the evolution of strand preference under finite diffusion. Interestingly, the results showed that selective forces "emerge" because of finite diffusion. Strikingly, the direction of the strand preference that evolves [i.e. (+) or (-) strand excess] is a complex non-monotonic function of the diffusion intensity. The mechanism underlying this behavior is elucidated. Furthermore, a speciation-like phenomenon is observed under certain conditions: two extreme replication strategies, namely replicase producers and template producers, emerge and coexist among competing replicators.
Finite diffusion enables the evolution of strand preference, the direction of which is a non-monotonic function of the diffusion intensity. By identifying the conditions under which strand preference evolves, this study provides an insight into how a rudimentary transcription-like pattern might have emerged in an RNA-based replicator system.
This article was reviewed by Eugene V Koonin, Rob Kinght and István Scheuring (nominated by David H Ardell). For the full reviews, please go to the Reviewers' comments section.
It is still not clear how prebiotic replicators evolved towards the complexity found in present day organisms. Within the most realistic scenario for prebiotic evolution, known as the RNA world hypothesis, such complexity has arisen from replicators consisting solely of RNA. Within contemporary life, remarkably many RNAs are involved in modifying other RNAs. In hindsight, such RNA-RNA modification might have helped in alleviating the limits of complexity posed by the information threshold for RNA-only replicators. Here we study the possible role of such self-modification in early evolution, by modeling the evolution of protocells as evolving replicators, which have the opportunity to incorporate these mechanisms as a molecular tool. Evolution is studied towards a set of 25 arbitrary ‘functional’ structures, while avoiding all other (misfolded) structures, which are considered to be toxic and increase the death-rate of a protocell. The modeled protocells contain a genotype of different RNA-sequences while their phenotype is the ensemble of secondary structures they can potentially produce from these RNA-sequences. One of the secondary structures explicitly codes for a simple sequence-modification tool. This ‘RNA-adapter’ can block certain positions on other RNA-sequences through antisense base-pairing. The altered sequence can produce an alternative secondary structure, which may or may not be functional. We show that the modifying potential of interacting RNA-sequences enables these protocells to evolve high fitness under high mutation rates. Moreover, our model shows that because of toxicity of misfolded molecules, redundant coding impedes the evolution of self-modification machinery, in effect restraining the evolvability of coding structures. Hence, high mutation rates can actually promote the evolution of complex coding structures by reducing redundant coding. Protocells can successfully use RNA-adapters to modify their genotype-phenotype mapping in order to enhance the coding capacity of their genome and fit more information on smaller sized genomes.
The discovery of ribozymes strengthened the RNA world hypothesis, which assumes that these precursors of modern life both stored information and acted as catalysts. For the first time among extensive studies on ribozymes, we have investigated the influence of hydrostatic pressure on the hairpin ribozyme catalytic activity. High pressures are of interest when studying life under extreme conditions and may help to understand the behavior of macromolecules at the origins of life. Kinetic studies of the hairpin ribozyme self-cleavage were performed under high hydrostatic pressure. The activation volume of the reaction (34 ± 5 ml/mol) calculated from these experiments is of the same order of magnitude as those of common protein enzymes, and reflects an important compaction of the RNA molecule during catalysis, associated to a water release. Kinetic studies were also carried out under osmotic pressure and confirmed this interpretation and the involvement of water movements (78 ± 4 water molecules per RNA molecule). Taken together, these results are consistent with structural studies indicating that loops A and B of the ribozyme come into close contact during the formation of the transition state. While validating baro-biochemistry as an efficient tool for investigating dynamics at work during RNA catalysis, these results provide a complementary view of ribozyme catalytic mechanisms.
The aminoacyl-tRNA synthetases are one of the major protein components in the translation machinery. These essential proteins are found in all forms of life and are responsible for charging their cognate tRNAs with the correct amino acid. The evolution of the tRNA synthetases is of fundamental importance with respect to the nature of the biological cell and the transition from an RNA world to the modern world dominated by protein-enzymes. We present a structure-based phylogeny of the aminoacyl-tRNA synthetases. By using structural alignments of all of the aminoacyl-tRNA synthetases of known structure in combination with a new measure of structural homology, we have reconstructed the evolutionary history of these proteins. In order to derive unbiased statistics from the structural alignments, we introduce a multidimensional QR factorization which produces a nonredundant set of structures. Since protein structure is more highly conserved than protein sequence, this study has allowed us to glimpse the evolution of protein structure that predates the root of the universal phylogenetic tree. The extensive sequence-based phylogenetic analysis of the tRNA synthetases (Woese et al., Microbiol. Mol. Biol. Rev. 64:202-236, 2000) has further enabled us to reconstruct the complete evolutionary profile of these proteins and to make connections between major evolutionary events and the resulting changes in protein shape. We also discuss the effect of functional specificity on protein shape over the complex evolutionary course of the tRNA synthetases.
All eukaryotes require mitochondria for survival and growth. The origin of mitochondria can be traced down to a single endosymbiotic event between two probably prokaryotic organisms. Subsequent evolution has left mitochondria a collection of heterogeneous organelle variants. Most of these variants have retained their own genome and translation system. In hydrogenosomes and mitosomes, however, the entire genome was lost. All types of mitochondria import most of their proteome from the cytosol, irrespective of whether they have a genome or not. Moreover, in most eukaryotes, a variable number of tRNAs that are required for mitochondrial translation are also imported. Thus, import of macromolecules, both proteins and tRNA, is essential for mitochondrial biogenesis. Here, we review what is known about the evolutionary history of the two processes using a recently revised eukaryotic phylogeny as a framework. We discuss how the processes of protein import and tRNA import relate to each other in an evolutionary context.
mitochondria; protein import; tRNA import; mitosomes; hydrogenosomes
The world's river dolphins (Inia, Pontoporia, Lipotes and Platanista) are among the least known and most endangered of all cetaceans. The four extant genera inhabit geographically disjunct river systems and exhibit highly modified morphologies, leading many cetologists to regard river dolphins as an unnatural group. Numerous arrangements have been proposed for their phylogenetic relationships to one another and to other odontocete cetaceans. These alternative views strongly affect the biogeographical and evolutionary implications raised by the important, although limited, fossil record of river dolphins. We present a hypothesis of river dolphin relationships based on phylogenetic analysis of three mitochondrial genes for 29 cetacean species, concluding that the four genera represent three separate, ancient branches in odontocete evolution. Our molecular phylogeny corresponds well with the first fossil appearances of the primary lineages of modern odontocetes. Integrating relevant events in Tertiary palaeoceanography, we develop a scenario for river dolphin evolution during the globally high sea levels of the Middle Miocene. We suggest that ancestors of the four extant river dolphin lineages colonized the shallow epicontintental seas that inundated the Amazon, Paraná, Yangtze and Indo-Gangetic river basins, subsequently remaining in these extensive waterways during their transition to freshwater with the Late Neogene trend of sea-level lowering.
Understanding the origin of protein synthesis has been notoriously difficult. We have taken as a starting premise Wolf and Koonin's view that "evolution of the translation system is envisaged to occur in a compartmentalized ensemble of replicating, co-selected RNA segments, i.e., in an RNA world containing ribozymes with versatile activities".
Presentation of the hypothesis
We propose that coded protein synthesis arose from a noncoded process in an RNA world as a natural consequence of the accumulation of a range of early tRNAs and their serendipitous RNA binding partners. We propose that, initially, RNA molecules with 3' CCA termini that could be aminoacylated by ribozymes, together with an ancestral peptidyl transferase ribozyme, produced small peptides with random or repetitive sequences. Our concept is that the first tRNA arose in this context from the ligation of two RNA hairpins and could be similarly aminoacylated at its 3' end to become a substrate for peptidyl transfer catalyzed by the ancestral ribozyme. Within this RNA world we hypothesize that proto-mRNAs appeared first simply as serendipitous binding partners, forming complementary base pair interactions with the anticodon loops of tRNA pairs. Initially this may have enhanced stability of the paired tRNA molecules so they were held together in close proximity, better positioning the 3' CCA termini for peptidyl transfer and enhancing the rate of peptide synthesis. If there were a selective advantage for the ensemble through the peptide products synthesized, it would provide a natural pathway for the evolution of a coding system with the expansion of a cohort of different tRNAs and their binding partners. The whole process could have occurred quite unremarkably for such a profound acquisition.
Testing the hypothesis
It should be possible to test the different parts of our model using the isolated contemporary 50S ribosomal subunit initially, and then with RNAs transcribed in vitro together with a minimal set of ribosomal proteins that are required today to support protein synthesis.
Implications of the hypothesis
This model proposes that genetic coding arose de novo from complementary base pair interactions between tRNAs and single-stranded RNAs present in the immediate environment.
This article was reviewed by Eugene Koonin, Rob Knight and Berthold Kastner (nominated by Laura Landweber).
Small nucleolar (sno)RNAs are required for posttranscriptional processing and modification of ribosomal, spliceosomal and messenger RNAs. Their presence in both eukaryotes and archaea indicates that snoRNAs are evolutionarily ancient. The location of some snoRNAs within the introns of ribosomal protein genes has been suggested to belie an RNA world origin, with the exons of the earliest protein-coding genes having evolved around snoRNAs after the advent of templated protein synthesis. Alternatively, this intronic location may reflect more recent selection for coexpression of snoRNAs and ribosomal components, ensuring rRNA modification by snoRNAs during ribosome synthesis. To gain insight into the evolutionary origins of this genetic organization, we examined the antiquity of snoRNA families and the stability of their genomic location across 44 eukaryote genomes.
We report that dozens of snoRNA families are traceable to the Last Eukaryotic Common Ancestor (LECA), but find only weak similarities between the oldest eukaryotic snoRNAs and archaeal snoRNA-like genes. Moreover, many of these LECA snoRNAs are located within the introns of host genes independently traceable to the LECA. Comparative genomic analyses reveal the intronic location of LECA snoRNAs is not ancestral however, suggesting the pattern we observe is the result of ongoing intragenomic mobility. Analysis of human transcriptome data indicates that the primary requirement for hosting intronic snoRNAs is a broad expression profile. Consistent with ongoing mobility across broadly-expressed genes, we report a case of recent migration of a non-LECA snoRNA from the intron of a ubiquitously expressed non-LECA host gene into the introns of two LECA genes during the evolution of primates.
Our analyses show that snoRNAs were a well-established family of RNAs at the time when eukaryotes began to diversify. While many are intronic, this association is not evolutionarily stable across the eukaryote tree; ongoing intragenomic mobility has erased signal of their ancestral gene organization, and neither introns-first nor evolved co-expression adequately explain our results. We therefore present a third model — constrained drift — whereby individual snoRNAs are intragenomically mobile and may occupy any genomic location from which expression satisfies phenotype.
snoRNA; Last Eukaryotic Common Ancestor; Intron; Retrotransposition; Introns-first; Constrained drift
The translation machinery underlies a multitude of biological processes within the cell. The design and implementation of the modern translation apparatus on even the simplest course of action is extremely complex, and involves different RNA and protein factors. According to the “RNA world” idea, the critical link in the translation machinery may be assigned to an adaptor tRNA molecule. Its exceptional functional and structural characteristics are of primary importance in understanding the evolutionary relationships among all these macromolecular components.
Presentation of the hypothesis
The 2′-3′ hydroxyls of the tRNA A76 constitute chemical groups of critical functional importance, as they are implicated in almost all phases of protein biosynthesis. They contribute to: a) each step of the tRNA aminoacylation reaction catalyzed by aminoacyl-tRNA synthetases (aaRSs); b) the isomerase activity of EF-Tu, involving a mixture of the 2′(3′)- aminoacyl tRNA isomers as substrates, thereby producing the required combination of amino acid and tRNA; and c) peptide bond formation at the peptidyl transferase center (PTC) of the ribosome. We hypothesize that specific functions assigned to the 2′-3′ hydroxyls during peptide bond formation co-evolved, together with two modes of attack on the aminoacyl-adenylate carbonyl typical for two classes of aaRSs, and alongside the isomerase activity of EF-Tu. Protein components of the translational apparatus are universally recognized as being of ancient origin, possibly replacing RNA-based enzymes that may have existed before the last universal common ancestor (LUCA). We believe that a remnant of these processes is still imprinted on the organization of modern-day translation.
Testing and implications of the hypothesis
Earlier publications indicate that it is possible to select ribozymes capable of attaching the aa-AMP moiety to RNA molecules. The scenario described herein would gain general acceptance, if a ribozyme able to activate the amino acid and transfer it onto the terminal ribose of the tRNA, would be found in any life form, or generated in vitro. Interestingly, recent studies have demonstrated the plausibility of using metals, likely abandoned under primordial conditions, as biomimetic catalysts of the aminoacylation reaction.
This article was reviewed by Henri Grosjean, Manuel Santos and Eugene Koonin. For complete reviews, go to the Reviewers’ reports section.
Aminoacyl-tRNA synthetases; Elongation factor EF-Tu; Ribosome; 2′-3′ hydroxyls of the ribose
It is generally believed that life first evolved from single-stranded RNA (ssRNA) that both stored genetic information and catalyzed the reactions required for self-replication.
Presentation of the hypothesis
By modeling early genome evolution on the engineering paradigm design-by-contract, an alternative scenario is presented in which life started with the appearance of double-stranded RNA (dsRNA) as an informational storage molecule while catalytic single-stranded RNA was derived from this dsRNA template later in evolution.
Testing the hypothesis
It was investigated whether this scenario could be implemented mechanistically by starting with abiotic processes. Double-stranded RNA could be formed abiotically by hybridization of oligoribonucleotides that are subsequently non-enzymatically ligated into a double-stranded chain. Thermal cycling driven by the diurnal temperature cycles could then replicate this dsRNA when strands of dsRNA separate and later rehybridize and ligate to reform dsRNA. A temperature-dependent partial replication of specific regions of dsRNA could produce the first template-based generation of catalytic ssRNA, similar to the developmental gene transcription process. Replacement of these abiotic processes by enzymatic processes would guarantee functional continuity. Further transition from a dsRNA to a dsDNA world could be based on minor mutations in template and substrate recognition sites of an RNA polymerase and would leave all existing processes intact.
Implications of the hypothesis
Modeling evolution on a design pattern, the 'dsRNA first' hypothesis can provide an alternative mechanistic evolutionary scenario for the origin of our genome that preserves functional continuity.
This article was reviewed by Anthony Poole, Eugene Koonin and Eugene Shakhnovich
Segmentation is a common feature of disparate clades of metazoans, and its evolution is a central problem of evolutionary developmental biology. We evolved in silico regulatory networks by a mutation/selection process that just rewards the number of segment boundaries. For segmentation controlled by a static gradient, as in long-germ band insects, a cascade of adjacent repressors reminiscent of gap genes evolves. For sequential segmentation controlled by a moving gradient, similar to vertebrate somitogenesis, we invariably observe a very constrained evolutionary path or funnel. The evolved state is a cell autonomous ‘clock and wavefront' model, with the new attribute of a separate bistable system driven by an autonomous clock. Early stages in the evolution of both modes of segmentation are functionally similar, and simulations suggest a possible path for their interconversion. Our computation illustrates how complex traits can evolve by the incremental addition of new functions on top of pre-existing traits.
evolution; modeling; oscillations; segmentation; somitogenesis