Ádám Kun

Real ribozymes suggest a relaxed error threshold

The error threshold for replication, the critical copying fidelity below which the fittest genotype deterministically disappears, limits the length of the genome that can be maintained by selection. Primordial replication must have been error-prone, and so early replicators are thought to have been necessarily short. The error threshold also depends on the fitness landscape. In an RNA world, many neutral and compensatory mutations can raise the threshold, below which the functional phenotype, rather than a particular sequence, is still present. Here we show, on the basis of comparative analysis of two extensively mutagenized ribozymes, that with a copying fidelity of 0.999 per digit per replication the phenotypic error threshold rises well above 7,000 nucleotides, which permits the selective maintenance of a functionally rich riboorganism with a genome of more than 100 different genes, the size of a tRNA. This requires an order of magnitude of improvement in the accuracy of in vitro–generated polymerase ribozymes. Incidentally, this genome size coincides with that estimated for a minimal cell achieved by top-down analysis, omitting the genes dealing with translation.

THE EFFECT OF CLONAL INTEGRATION ON PLANT COMPETITION FOR MOSAIC HABITAT SPACE

Physiological integration between ramets has been observed in several clonal plant species. But consequences of integration on the competitive ability and spatial de- velopment of genets have received little attention so far. This study is an attempt to examine the population- and community-level implications of integration in a spatially explicit model. We have simulated different resource patterns in a cellular automata, varying the pro- portion (p) and size (s) of resource-rich patches and the average resource level in the area (h). We compared the efficiency of integrator to splitter genets in exploring and utilizing the resource patches. In the integrator, ramets that belonged to the same genet were phys- iologically connected and shared the resource taken up by any part of the genet. In the splitter, all ramets were autonomous, i.e., survival and reproduction of each ramet only depended on the local resource conditions. Thus, the integrator sensed and responded to environmental heterogeneity on a larger spatial scale than the splitter. Integration can be interpreted as sharing the risk of genet mortality among interconnected ramets, while split- ting represents risk spreading among autonomous ramets. In each simulated habitat type, we followed the course of competition between splitter and integrator genets for 500 gen- erations. First, we examined the effect of environmental heterogeneity on the result of compe- tition. We fixed the average resource level in the area and changed the spatial distribution of the resource by varying p and s. We found that the smaller the proportion of favorable sites, the better it is to integrate. But already a small deviation from random to clumped resource distribution (i.e., relatively small s) made the integrator competitively inferior to the splitter. In the next step, we varied the overall resource richness in the area. High productivity of the habitat promoted the dominance of integrators. The simulations dem- onstrated that there were habitat types in which one of the strategies (the integrator or the splitter) rapidly excluded its competitor. But at the medium range of environmental param- eters, long-term coexistence of the strategies became possible. As integration proceeded simultaneously with horizontal growth and exploration of new patches, integrators re- markably differed from splitters in their pattern of space occupation. A spatial statistical analysis revealed that splitters maintained strong spatial association with the resource: splitting promoted habitat selection. Integration, on the other hand, led to gap-filling, fu- gitive spatial behavior. For a range of realistic habitat patterns, we need not expect the exclusion of any of the pure strategies—splitters and integrators can coexist.

Computational identification of obligatorily autocatalytic replicators embedded in metabolic networks

BackgroundIf chemical A is necessary for the synthesis of more chemical A, then A has the power of replication (such systems are known as autocatalytic systems). We provide the first systems-level analysis searching for small-molecular autocatalytic components in the metabolisms of diverse organisms, including an inferred minimal metabolism.ResultsWe find that intermediary metabolism is invariably autocatalytic for ATP. Furthermore, we provide evidence for the existence of additional, organism-specific autocatalytic metabolites in the forms of coenzymes (NAD+, coenzyme A, tetrahydrofolate, quinones) and sugars. Although the enzymatic reactions of a number of autocatalytic cycles are present in most of the studied organisms, they display obligatorily autocatalytic behavior in a few networks only, hence demonstrating the need for a systems-level approach to identify metabolic replicators embedded in large networks.ConclusionMetabolic replicators are apparently common and potentially both universal and ancestral: without their presence, kick-starting metabolic networks is impossible, even if all enzymes and genes are present in the same cell. Identification of metabolic replicators is also important for attempts to create synthetic cells, as some of these autocatalytic molecules will presumably be needed to be added to the system as, by definition, the system cannot synthesize them without their initial presence.

Fragmentation of clones: how does it influence dispersal and competitive ability?

We applied individual-based simulations to study the effect of physiological integration among ramets in clonal species that live in patchy habitats. Three strategies were compared: (1) Splitter, in which the genet was fragmented into independent ramets; (2) Transient Integrator, where only groups of ramets were connected; and (3) Permanent Integrator, in which fragmentation did not occur, and the whole genet was integrated. We studied the dynamics of spatial spreading and population growth in these strategies separately and in competition. Various habitat types were modeled by changing the density of favorable habitat patches. We found that the spatial pattern of good patches significantly influenced the growth of the populations. When the resource patches were scarce, a large proportion of the carrying capacity of the habitat was not utilized by any of the strategies. It was the Splitter that proved to be the most severely dispersal-limited. But at the same time, it could compete for the good patches most efficiently. The balance between these two contradictory effects was largely determined by the proportion of favorable to unfavorable areas. When this proportion was low or intermediate (up to ca. 50% good), integration was more advantageous. At higher proportions, fragmentation became beneficial. Fragmentation into groups of ramets (Transient Integration) was not sufficient, only radical splitting could ensure a significant selective advantage. Transient Integrators got fragmented according to the spatial pattern of ramet mortality. It was interesting that the enrichment of the area in good sites did not lead to larger fragment sizes. It merely raised the number of fragments. Nevertheless, these small fragments were more similar to integrated genets (in the Permanent Integrator) than to solitary ramets (in the Splitter) in terms of dispersal and competitive ability. This suggests that even a slightly integrated clonal species can be ecologically considered as an integrator.

Exploration and exploitation of resource patches by clonal growth: A spatial model on the effect of transport between modules

Abstract Modular development in plants facilitates to cope with environmental heterogeneity. Differential natality and mortality of the modules in resource-rich versus poor sites can lead to selective occupancy of favorable habitat patches (foraging for good sites). In some species, especially in clonal plants, the modules are quite autonomous, and perceive and respond to local habitat conditions individually (splitter strategy). In others, the modules are physiologically integrated, and exchange water, nutrients and assimilates. In the simplest case, the resource moves from rich to poor sites, thus, the contrast between habitat patches is evened out within the plant (integrator strategy). Integration can significantly rearrange the pattern of resources that are available to the modules. We studied the effect of integration on the efficiency of foraging. We applied a spatially explicit (cellular automata) model, in which we varied the size and proportion of resource-rich patches in the habitat. In each simulation, a splitter and an integrator species were competing for this patchy resource. We compared the dynamics of module populations. We studied the spatial association between the splitter, the integrator, and the resource by an information statistical method of pattern analysis. Thus, we gained a quantitative description of habitat structure, and a related measure for the efficiency of foraging. We found that splitting always promoted foraging, but at the expense of slower population growth. This became critical when the distribution of resource patches was sparse. In these cases, the characteristically fugitive spatial behavior of the integrator facilitated its quick spreading into the gaps that has been left vacant by the splitter. Better tolerance of the integrator to resource scarcity, and better chance for colonizing distant patches enabled its long-term persistence, occasionally even dominance over the area. Therefore, the adaptive advantage of splitting versus integration depended sensitively on the spatial pattern of resource patches.

Evolution of cooperation on dynamical graphs

There are two key characteristic of animal and human societies: (1) degree heterogeneity, meaning that not all individual have the same number of associates; and (2) the interaction topology is not static, i.e. either individuals interact with different set of individuals at different times of their life, or at least they have different associations than their parents. Earlier works have shown that population structure is one of the mechanisms promoting cooperation. However, most studies had assumed that the interaction network can be described by a regular graph (homogeneous degree distribution). Recently there are an increasing number of studies employing degree heterogeneous graphs to model interaction topology. But mostly the interaction topology was assumed to be static. Here we investigate the fixation probability of the cooperator strategy in the prisoners dilemma, when interaction network is a random regular graph, a random graph or a scale-free graph and the interaction network is allowed to change. We show that the fixation probability of the cooperator strategy is lower when the interaction topology is described by a dynamical graph compared to a static graph. Even a limited network dynamics significantly decreases the fixation probability of cooperation, an effect that is mitigated stronger by degree heterogeneous networks topology than by a degree homogeneous one. We have also found that from the considered graph topologies the decrease of fixation probabilities due to graph dynamics is the lowest on scale-free graphs.

The dynamics of the RNA world: insights and challenges

The RNA world hypothesis of the origin of life, in which RNA emerged as both enzyme and information carrier, is receiving solid experimental support. The prebiotic synthesis of biomolecules, the catalytic aid offered by mineral surfaces, and the vast enzymatic repertoire of ribozymes are only pieces of the origin of life puzzle; the full picture can only emerge if the pieces fit together by either following from one another or coexisting with each other. Here, we review the theory of the origin, maintenance, and enhancement of the RNA world as an evolving population of dynamical systems. The dynamical view of the origin of life allows us to pinpoint the missing and the not fitting pieces: (1) How can the first self‐replicating ribozyme emerge in the absence of template‐directed information replication? (2) How can nucleotide replicators avoid competitive exclusion despite utilizing the very same resources (nucleobases)? (3) How can the information catastrophe be avoided? (4) How can enough genes integrate into a cohesive system in order to transition to a cellular stage? (5) How can the way information is stored and metabolic complexity coevolve to pave to road leading out of the RNA world to the present protein–DNA world?

Resource heterogeneity can facilitate cooperation

Although social structure is known to promote cooperation, by locally exposing selfish agents to their own deeds, studies to date assumed that all agents have access to the same level of resources. This is clearly unrealistic. Here we find that cooperation can be maintained when some agents have access to more resources than others. Cooperation can then emerge even in populations in which the temptation to defect is so strong that players would act fully selfishly if their resources were distributed uniformly. Resource heterogeneity can thus be crucial for the emergence and maintenance of cooperation. We also show that resource heterogeneity can hinder cooperation once the temptation to defect is significantly lowered. In all cases, the level of cooperation can be maximized by managing resource heterogeneity.

Transient compartmentalization of RNA replicators prevents extinction due to parasites

Beating the curse of the parasite The evolution of molecular replicators was a critical step in the origin of life. Such replicators would have suffered from faster-replicating “molecular parasites” outcompeting the parental replicator. Compartmentalization of replicators inside protocells would have helped ameliorate the effect of parasites. Matsumura et al. show that transient compartmentalization in nonbiological materials is sufficient to tame the problem of parasite takeover. They analyzed viral replication in a droplet-based microfluidic system, which revealed that as long as there is selection for a functional replicator, the population is not overwhelmed by the faster-replicating parasite genomes. Science, this issue p. 1293 Temporary compartmentalization in water drops prevents molecular replicators from being swamped by faster-replicating parasitic mutants. The appearance of molecular replicators (molecules that can be copied) was probably a critical step in the origin of life. However, parasitic replicators would take over and would have prevented life from taking off unless the replicators were compartmentalized in reproducing protocells. Paradoxically, control of protocell reproduction would seem to require evolved replicators. We show here that a simpler population structure, based on cycles of transient compartmentalization (TC) and mixing of RNA replicators, is sufficient to prevent takeover by parasitic mutants. TC tends to select for ensembles of replicators that replicate at a similar rate, including a diversity of parasites that could serve as a source of opportunistic functionality. Thus, TC in natural, abiological compartments could have allowed life to take hold.

Intermediate landscape disturbance maximizes metapopulation density

The viability of metapopulations in fragmented landscapes has become a central theme in conservation biology. Landscape fragmentation is increasingly recognized as a dynamical process: in many situations, the quality of local habitats must be expected to undergo continual changes. Here we assess the implications of such recurrent local disturbances for the equilibrium density of metapopulations. Using a spatially explicit lattice model in which the considered metapopulation as well as the underlying landscape pattern change dynamically, we show that equilibrium metapopulation density is maximized at intermediate frequencies of local landscape disturbance. On both sides around this maximum, the metapopulation may go extinct. We show how the position and shape of the intermediate viability maximum is responding to changes in the landscape’s overall habitat quality and the population’s propensity for local extinction. We interpret our findings in terms of a dual effect of intensified landscape disturbances, which on the one hand exterminate local populations and on the other hand enhance a metapopulation’s capacity for spreading between habitat clusters.