Evolution of RNA Viruses: Reasons for the Existence of Separate Plus, Minus, and Double-Strand Replication Strategies.

Plus, minus, and double-strand RNA viruses are all found in nature. We use computational models to study the relative success of these strategies. We consider translation, replication, and virion assembly inside one cell, and transmission of virions between cells.

Evolution of Bipartite and Segmented Viruses from Monopartite Viruses.

RNA viruses may be monopartite (all genes on one strand), multipartite (two or more strands packaged separately) or segmented (two or more strands packaged together). In this article, we consider competition between a complete monopartite virus, A, and two defective viruses, D and E, that have complementary genes. We use stochastic models that follow gene translation, RNA replication, virus assembly, and transmission between cells.

Rolling Circles as a Means of Encoding Genes in the RNA World.

The rolling circle mechanism found in viroids and some RNA viruses is a likely way that replication could have begun in the RNA World. Here, we consider simulations of populations of protocells, each containing multiple copies of rolling circle RNAs that can replicate non-enzymatically. The mechanism requires the presence of short self-cleaving ribozymes such as hammerheads, which can cleave and re-circularize RNA strands.

Computer simulations of Template-Directed RNA Synthesis driven by temperature cycling in diverse sequence mixtures.

We present simulations of non-enzymatic template-directed RNA synthesis that incorporate primer extension, ligation, melting, and reannealing. Strand growth occurs over multiple heating/cooling cycles, producing strands of several hundred nucleotides in length, starting with random oligomers of 4 to 10 nucleotides. A strand typically grows by only 1 or 2 nucleotides in each cycle.

When Is a Reaction Network a Metabolism? Criteria for Simple Metabolisms That Support Growth and Division of Protocells.

With the aim of better understanding the nature of metabolism in the first cells and the relationship between the origin of life and the origin of metabolism, we propose three criteria that a chemical reaction system must satisfy in order to constitute a metabolism that would be capable of sustaining growth and division of a protocell. (1) Biomolecules produced by the reaction system must be maintained at high concentration inside the cell while they remain at low or zero concentration outside. (2) The total solute concentration inside the cell must be higher than outside, so there is a positive osmotic pressure that drives cell growth.

Rolling-circle and strand-displacement mechanisms for non-enzymatic RNA replication at the time of the origin of life.

It is likely that RNA replication began non-enzymatically, and that polymerases were later selected to speed up the process. We consider replication mechanisms in modern viruses and ask which of these is possible non-enzymatically, using mathematical models and experimental data found in the literature to estimate rates of RNA synthesis and replication. Replication via alternating plus and minus strands is found in some single-stranded RNA viruses.

Can the RNA World Still Function without Cytidine?

Most scenarios for the origin of life assume that RNA played a key role in both catalysis and information storage. The A, U, G, and C nucleobases in modern RNA all participate in secondary structure formation and replication. However, the rapid deamination of C to U and the absence of C in meteorite samples suggest that prebiotic RNA may have been deficient in cytosine.

Survival of RNA Replicators is much Easier in Protocells than in Surface-Based, Spatial Systems.

In RNA-World scenarios for the origin of life, replication is catalyzed by polymerase ribozymes. Replicating RNA systems are subject to invasion by non-functional parasitic strands. It is well-known that there are two ways to avoid the destruction of the system by parasites: spatial clustering in models with limited diffusion, or group selection in protocells.

Evolution of protein interfaces in multimers and fibrils.

A majority of cellular proteins function as part of multimeric complexes of two or more subunits. Multimer formation requires interactions between protein surfaces that lead to closed structures, such as dimers and tetramers. If proteins interact in an open-ended way, uncontrolled growth of fibrils can occur, which is likely to be detrimental in most cases.

The evolution of antibiotic production rate in a spatial model of bacterial competition.

We consider competition between antibiotic producing bacteria, non-producers (or cheaters), and sensitive cells in a two-dimensional lattice model. Previous work has shown that these three cell types can survive in spatial models due to the presence of spatial patterns, whereas coexistence is not possible in a well-mixed system. We extend this to consider the evolution of the antibiotic production rate, assuming that the cost of antibiotic production leads to a reduction in growth rate of the producers.

Constraining the Time Interval for the Origin of Life on Earth.

Estimates of the time at which life arose on Earth make use of two types of evidence. First, astrophysical and geophysical studies provide a timescale for the formation of Earth and the Moon, for large impact events on early Earth, and for the cooling of the early magma ocean. From this evidence, we can deduce a habitability boundary, which is the earliest point at which Earth became habitable.

The Role of Templating in the Emergence of RNA from the Prebiotic Chemical Mixture.

Biological RNA is a uniform polymer in three senses: it uses nucleotides of a single chirality; it uses only ribose sugars and four nucleobases rather than a mixture of other sugars and bases; and it uses only 3'-5' bonds rather than a mixture of different bond types. We suppose that prebiotic chemistry would generate a diverse mixture of potential monomers, and that random polymerization would generate non-uniform strands of mixed chirality, monomer composition, and bond type. We ask what factors lead to the emergence of RNA from this mixture.

Chemical Evolution and the Evolutionary Definition of Life.

Darwinian evolution requires a mechanism for generation of diversity in a population, and selective differences between individuals that influence reproduction. In biology, diversity is generated by mutations and selective differences arise because of the encoded functions of the sequences (e.g.

Error thresholds for RNA replication in the presence of both point mutations and premature termination errors.

We consider a spatial model of replication in the RNA World in which polymerase ribozymes use neighbouring strands as templates. Point mutation errors create parasites that have the same replication rate as the polymerase. We have shown previously that spatial clustering allows survival of the polymerases as long as the error rate is below a critical error threshold.

Co-operation between Polymerases and Nucleotide Synthetases in the RNA World.

It is believed that life passed through an RNA World stage in which replication was sustained by catalytic RNAs (ribozymes). The two most obvious types of ribozymes are a polymerase, which uses a neighbouring strand as a template to make a complementary sequence to the template, and a nucleotide synthetase, which synthesizes monomers for use by the polymerase. When a chemical source of monomers is available, the polymerase can survive on its own.

The Effect of Limited Diffusion and Wet-Dry Cycling on Reversible Polymerization Reactions: Implications for Prebiotic Synthesis of Nucleic Acids.

A long-standing problem for the origins of life is that polymerization of many biopolymers, including nucleic acids and peptides, is thermodynamically unfavourable in aqueous solution. If bond making and breaking is reversible, monomers and very short oligomers predominate. Recent experiments have shown that wetting and drying cycles can overcome this problem and drive the formation of longer polymers.

Estimating the Frequency of Horizontal Gene Transfer Using Phylogenetic Models of Gene Gain and Loss.

We analyze patterns of gene presence and absence in a maximum likelihood framework with rate parameters for gene gain and loss. Standard methods allow independent gains and losses in different parts of a tree. While losses of the same gene are likely to be frequent, multiple gains need to be considered carefully.

Pathways of Genetic Code Evolution in Ancient and Modern Organisms.

There have been two distinct phases of evolution of the genetic code: an ancient phase--prior to the divergence of the three domains of life, during which the standard genetic code was established--and a modern phase, in which many alternative codes have arisen in specific groups of genomes that differ only slightly from the standard code. Here we discuss the factors that are most important in these two phases, and we argue that these are substantially different. In the modern phase, changes are driven by chance events such as tRNA gene deletions and codon disappearance events.

The RNA World: molecular cooperation at the origins of life.

The RNA World concept posits that there was a period of time in primitive Earth's history - about 4 billion years ago - when the primary living substance was RNA or something chemically similar. In the past 50 years, this idea has gone from speculation to a prevailing idea. In this Review, we summarize the key logic behind the RNA World and describe some of the most important recent advances that have been made to support and expand this logic.

The origin and spread of a cooperative replicase in a prebiotic chemical system.

The origin of life requires the emergence of a system of autocatalytic polymers such as RNA. We consider a trans-acting replicase that catalyses replication of a template (either a copy of itself or another sequence). Our model includes alternating plus/minus strand replication where only the plus strand is a catalyst.

Contributions of speed and accuracy to translational selection in bacteria.

Among bacteria, we have previously shown that species that are capable of rapid growth have stronger selection on codon usage than slow growing species, and possess higher numbers of rRNA and tRNA genes. This suggests that fast-growers are adapted for fast protein synthesis. There is also considerable evidence that codon usage is influenced by accuracy of translation, and some authors have argued that accuracy is more important than speed.

The origin of life is a spatially localized stochastic transition.

Background: Life depends on biopolymer sequences as catalysts and as genetic material. A key step in the Origin of Life is the emergence of an autocatalytic system of biopolymers. Here we study computational models that address the way a living autocatalytic system could have emerged from a non-living chemical system, as envisaged in the RNA World hypothesis.

The importance of stochastic transitions for the origin of life.

We discuss the origin of life in terms of an RNA World scenario in which the creation of autocatalytic sequences is the key step. Our computational models illustrate that life arises by a rare stochastic event that occurs due to spatially localized concentration fluctuations. This allows the chemical system to jump from a non-living state with very low ribozyme concentration to a living state that is controlled by ribozymes.

Autocatalytic replication and homochirality in biopolymers: is homochirality a requirement of life or a result of it?

A key step in the origin of life is the establishment of autocatalytic cycles controlled by biopolymer catalysts. These catalysts (either ribozymes or proteins) are composed of homochiral monomers. Homochirality in living systems is maintained because biopolymers are asymmetric in their catalysis and synthesize molecules of their own handedness.

Testing the infinitely many genes model for the evolution of the bacterial core genome and pangenome.

When groups of related bacterial genomes are compared, the number of core genes found in all genomes is usually much less than the mean genome size, whereas the size of the pangenome (the set of genes found on at least one of the genomes) is much larger than the mean size of one genome. We analyze 172 complete genomes of Bacilli and compare the properties of the pangenomes and core genomes of monophyletic subsets taken from this group. We then assess the capabilities of several evolutionary models to predict these properties.