The RNA-DNA world and the emergence of DNA-encoded heritable traits.

The RNA world hypothesis confers a central role to RNA molecules in information encoding and catalysis. Even though evidence in support of this hypothesis has accumulated from both experiments and computational modelling, the transition from an RNA world to a world where heritable genetic information is encoded in DNA remains an open question. Recent experiments show that both RNA and DNA templates can extend complementary primers using free RNA/DNA nucleotides, either non-enzymatically or in the presence of a replicase ribozyme. Guided by these experiments, we analyse protocellular evolution with an expanded set of reaction pathways made possible through the presence of DNA nucleotides. By encapsulating these reactions inside three different types of protocellular compartments, each subject to distinct modes of selection, we show how protocells containing DNA-encoded replicases in low copy numbers and replicases in high copy numbers can dominate the population. This is facilitated by a reaction that leads to auto-catalytic synthesis of replicase ribozymes from DNA templates encoding the replicase after the chance emergence of a replicase through non-enzymatic reactions. Our work unveils a pathway for the transition from an RNA world to a mixed RNA-DNA world characterized by Darwinian evolution, where DNA sequences encode heritable phenotypes.

The Effect of Environment on the Evolution and Proliferation of Protocells of Increasing Complexity.

The formation, growth, division and proliferation of protocells containing RNA strands is an important step in ensuring the viability of a mixed RNA-lipid world. Experiments and computer simulations indicate that RNA encapsulated inside protocells can favor the protocell, promoting its growth while protecting the system from being over-run by selfish RNA sequences. Recent work has also shown that the rolling-circle replication mechanism can be harnessed to ensure the rapid growth of RNA strands and the probabilistic emergence and proliferation of protocells with functionally diverse ribozymes. Despite these advances in our understanding of a primordial RNA-lipid world, key questions remain about the ideal environment for the formation of protocells and its role in regulating the proliferation of functionally complex protocells. The hot spring hypothesis suggests that mineral-rich regions near hot springs, subject to dry-wet cycles, provide an ideal environment for the origin of primitive protocells. We develop a computational model to study protocellular evolution in such environments that are distinguished by the occurrence of three distinct phases, a wet phase, followed by a gel phase, and subsequently by a dry phase. We determine the conditions under which protocells containing multiple types of ribozymes can evolve and proliferate in such regions. We find that diffusion in the gel phase can inhibit the proliferation of complex protocells with the extent of inhibition being most significant when a small fraction of protocells is eliminated during environmental cycling. Our work clarifies how the environment can shape the evolution and proliferation of complex protocells.

Evolution towards increasing complexity through functional diversification in a protocell model of the RNA world.

The encapsulation of genetic material inside compartments together with the creation and sustenance of functionally diverse internal components are likely to have been key steps in the formation of 'live', replicating protocells in an RNA world. Several experiments have shown that RNA encapsulated inside lipid vesicles can lead to vesicular growth and division through physical processes alone. Replication of RNA inside such vesicles can produce a large number of RNA strands. Yet, the impact of such replication processes on the emergence of the first ribozymes inside such protocells and on the subsequent evolution of the protocell population remains an open question. In this paper, we present a model for the evolution of protocells with functionally diverse ribozymes. Distinct ribozymes can be created with small probabilities during the error-prone RNA replication process via the rolling circle mechanism. We identify the conditions that can synergistically enhance the number of different ribozymes inside a protocell and allow functionally diverse protocells containing multiple ribozymes to dominate the population. Our work demonstrates the existence of an effective pathway towards increasing complexity of protocells that might have eventually led to the origin of life in an RNA world.

Emergence of ribozyme and tRNA-like structures from mineral-rich muddy pools on prebiotic earth.

The RNA world hypothesis, although a viable one regarding the origin of life on earth, has so far failed to provide a compelling explanation for the synthesis of RNA enzymes from free nucleotides via abiotic processes. To tackle this long-standing problem, we develop a realistic model for the onset of the RNA world, using experimentally determined rates for polymerization reactions. We start with minimal assumptions about the initial state that only requires the presence of short oligomers or just free nucleotides and consider the effects of environmental cycling by dividing a day into a dry, semi-wet and wet phases that are distinguished by the nature of reactions they support. Long polymers, with maximum lengths sometimes exceeding 100 nucleotides, spontaneously emerge due to a combination of non-enzymatic, non-templated polymer extension and template-directed primer extension processes. The former helps in increasing the lengths of RNA strands, whereas the later helps in producing complementary copies of the strands. Strands also undergo hydrolysis in a structure-dependent manner that favour breaking of bonds connecting unpaired nucleotides. We identify the most favourable conditions needed for the emergence of ribozyme and tRNA-like structures and double stranded RNA molecules, classify all RNA strands on the basis of their secondary structures and determine their abundance in the population. Our results indicate that under suitable environmental conditions, non-enzymatic processes would have been sufficient to lead to the emergence of a variety of ribozyme-like molecules with complex secondary structures and potential catalytic functions.