Spontaneous network formation among cooperative RNA replicators.

The origins of life on Earth required the establishment of self-replicating chemical systems capable of maintaining and evolving biological information. In an RNA world, single self-replicating RNAs would have faced the extreme challenge of possessing a mutation rate low enough both to sustain their own information and to compete successfully against molecular parasites with limited evolvability. Thus theoretical analyses suggest that networks of interacting molecules were more likely to develop and sustain life-like behaviour. Here we show that mixtures of RNA fragments that self-assemble into self-replicating ribozymes spontaneously form cooperative catalytic cycles and networks. We find that a specific three-membered network has highly cooperative growth dynamics. When such cooperative networks are competed directly against selfish autocatalytic cycles, the former grow faster, indicating an intrinsic ability of RNA populations to evolve greater complexity through cooperation. We can observe the evolvability of networks through in vitro selection. Our experiments highlight the advantages of cooperative behaviour even at the molecular stages of nascent life.

Stochastic evolutionary dynamics resolve the Traveler's Dilemma.

Behavior in social dilemmas is often inconsistent with the predictions of classical game theory: people (and a wide variety of other organisms) are more cooperative than might be expected. Here we consider behavior in one such social dilemma, the Traveler's Dilemma, that has received considerable attention in the economics literature but is little known among theoretical biologists. The rules of the game are as follows. Two players each choose a value between R and M, where 0

Prebiotically plausible mechanisms increase compositional diversity of nucleic acid sequences.

During the origin of life, the biological information of nucleic acid polymers must have increased to encode functional molecules (the RNA world). Ribozymes tend to be compositionally unbiased, as is the vast majority of possible sequence space. However, ribonucleotides vary greatly in synthetic yield, reactivity and degradation rate, and their non-enzymatic polymerization results in compositionally biased sequences. While natural selection could lead to complex sequences, molecules with some activity are required to begin this process. Was the emergence of compositionally diverse sequences a matter of chance, or could prebiotically plausible reactions counter chemical biases to increase the probability of finding a ribozyme? Our in silico simulations using a two-letter alphabet show that template-directed ligation and high concatenation rates counter compositional bias and shift the pool toward longer sequences, permitting greater exploration of sequence space and stable folding. We verified experimentally that unbiased DNA sequences are more efficient templates for ligation, thus increasing the compositional diversity of the pool. Our work suggests that prebiotically plausible chemical mechanisms of nucleic acid polymerization and ligation could predispose toward a diverse pool of longer, potentially structured molecules. Such mechanisms could have set the stage for the appearance of functional activity very early in the emergence of life.

Inhibition of bacterial conjugation by phage M13 and its protein g3p: quantitative analysis and model.

Conjugation is the main mode of horizontal gene transfer that spreads antibiotic resistance among bacteria. Strategies for inhibiting conjugation may be useful for preserving the effectiveness of antibiotics and preventing the emergence of bacterial strains with multiple resistances. Filamentous bacteriophages were first observed to inhibit conjugation several decades ago. Here we investigate the mechanism of inhibition and find that the primary effect on conjugation is occlusion of the conjugative pilus by phage particles. This interaction is mediated primarily by phage coat protein g3p, and exogenous addition of the soluble fragment of g3p inhibited conjugation at low nanomolar concentrations. Our data are quantitatively consistent with a simple model in which association between the pili and phage particles or g3p prevents transmission of an F plasmid encoding tetracycline resistance. We also observe a decrease in the donor ability of infected cells, which is quantitatively consistent with a reduction in pili elaboration. Since many antibiotic-resistance factors confer susceptibility to phage infection through expression of conjugative pili (the receptor for filamentous phage), these results suggest that phage may be a source of soluble proteins that slow the spread of antibiotic resistance genes.

The basic reproductive ratio of life.

Template-directed polymerization of nucleotides is believed to be a pathway for the replication of genetic material in the earliest cells. We assume that activated monomers are produced by prebiotic chemistry. These monomers can undergo spontaneous polymerization, a system that we call "prelife." Adding template-directed polymerization changes the equilibrium structure of prelife if the rate constants meet certain criteria. In particular, if the basic reproductive ratio of sequences of a certain length exceeds one, then those sequences can attain high abundance. Furthermore, if many sequences replicate, then the longest sequences can reach high abundance even if the basic reproductive ratios of all sequences are less than one. We call this phenomenon "subcritical life." Subcritical life suggests that sequences long enough to be ribozymes can become abundant even if replication is relatively inefficient. Our work on the evolution of replication has interesting parallels to infection dynamics. Life (replication) can be seen as an infection of prelife.