Conceptualizing the origin of life in terms of evolution.

In this opinion piece, we discuss how to place evolution in the context of origin-of-life research. Our discussion starts with a popular definition: 'life is a self-sustained chemical system capable of undergoing Darwinian evolution'. According to this definition, the origin of life is the same as the origin of evolution: evolution is the 'end' of the origin of life. This perspective, however, has a limitation, in that the ability of evolution in and of itself is insufficient to explain the origin of life as we know it, as indicated by Spiegelman's and Lincoln and Joyce's experiments. This limitation provokes a crucial question: What conditions are required for replicating systems to evolve into life? From this perspective, the origin of life includes the emergence of life through evolution: evolution is a 'means' of the origin of life. After reviewing Eigen's pioneering work on this question, we mention our ongoing work suggesting that a key condition might be conflicting multi-level evolution. Taken together, there are thus two questions regarding the origin of life: how evolution gets started, and how evolution produces life. Evolution is, therefore, at the centre of the origin of life, where the two lines of enquiry must meet.This article is part of the themed issue 'Reconceptualizing the origins of life'.

Large changes in regulome size herald the main prokaryotic lineages.

Using a large-scale reconstruction of ancestral gene content, we show that radical changes in regulome size occur at the origins of major prokaryotic lineages. Subsequently, the duplication and deletion of regulators slows down in most lineages, except proteobacteria, significantly reducing the scaling of regulators and keeping their average proportion lineage-specific. Our results also suggest that major transitions in prokaryote evolution are related to changes in regulatory capacity rather than proteome innovations.

In silico evolved lac operons exhibit bistability for artificial inducers, but not for lactose.

Bistability in the lac operon of Escherichia coli has been widely studied, both experimentally and theoretically. Experimentally, bistability has been observed when E. coli is induced by an artificial, nonmetabolizable, inducer. However, if the lac operon is induced with lactose, the natural inducer, bistability has not been demonstrated. We derive an analytical expression that can predict the occurrence of bistability both for artificial inducers and lactose. We find very different conditions for bistability in the two cases. Indeed, for artificial inducers bistability is predicted, but for lactose the condition for bistability is much more difficult to satisfy. Moreover, we demonstrate that in silico evolution of the lac operon generates an operon that avoids bistability with respect to lactose, but does exhibit bistability with respect to artificial inducers. The activity of this evolved operon strikingly resembles the experimentally observed activity of the operon. Thus our computational experiments suggest that the wild-type lac operon, which regulates lactose metabolism, is not a bistable switch. Nevertheless, for engineering purposes, this operon can be used as a bistable switch with artificial inducers.

How amoeboids self-organize into a fruiting body: multicellular coordination in Dictyostelium discoideum.

When individual amoebae of the cellular slime mold Dictyostelium discoideum are starving, they aggregate to form a multicellular migrating slug, which moves toward a region suitable for culmination. The culmination of the morphogenesis involves complex cell movements that transform a mound of cells into a globule of spores on a slender stalk. The movement has been likened to a "reverse fountain," whereby prestalk cells in the upper part form a stalk that moves downwards and anchors to the substratum, while prespore cells in the lower part move upwards to form the spore head. So far, however, no satisfactory explanation has been produced for this process. Using a computer simulation that we developed, we now demonstrate that the processes that are essential during the earlier stages of the morphogenesis are in fact sufficient to produce the dynamics of the culmination stage. These processes are cAMP signaling, differential adhesion, cell differentiation, and production of extracellular matrix. Our model clarifies the processes that generate the observed cell movements. More specifically, we show that periodic upward movements, caused by chemotactic motion, are essential for successful culmination, because the pressure waves they induce squeeze the stalk downwards through the cell mass. The mechanisms revealed by our model have a number of self-organizing and self-correcting properties and can account for many previously unconnected and unexplained experimental observations.

Individual- and population-based diversity in restriction-modification systems.

Restriction-modification (RM) systems are cognate gene complexes that code for an endonuclease and a methylase. They are often thought to have developed in bacteria as protection against invading genetic material, e.g., phage DNA. The high diversity of RM systems, as observed in nature, is often ascribed to the coevolution of RM systems (which 'invent' novel types) and phages. However, the extent to which phages are insensitive to RM systems casts doubts on the effectiveness of RM systems as protection against infection and thereby on the reason for the diversity of RM systems. We present an eco-evolutionary model in order to study the evolution of the diversity of RM systems. The model predicts that in general diversity of RM systems is high. More importantly, the diversity of the RM systems is expressed either at the individual level or at the population level. In the first case all individuals carry RM systems of all sequence specificities, whereas in the second case they carry only one RM system or no RM systems at all. Nevertheless, in the second case the same number of sequence specificities are present in the population.

Shapes in the shadow: evolutionary dynamics of morphogenesis.

This article investigates the evolutionary dynamics of morphogenesis. In this study, morphogenesis arises as a side-effect of maximization of number of cell types. Thus, it investigates the evolutionary dynamics of side-effects. Morphogenesis is governed by the interplay between differential cell adhesion, gene-regulation, and intercellular signaling. Thus, it investigates the potential to generate complex behavior by entanglement of relatively "boring" processes, and the (automatic) coordination between these processes. The evolutionary dynamics shows all the hallmarks of evolutionary dynamics governed by nonlinear genotype phenotype mapping: for example, punctuated equilibria and diffusion on neutral paths. More striking is the result that interesting, complex morphogenesis occurs mainly in the "shadow" of neutral paths which preserve cell differentiation, that is, the interesting morphologies arise as mutants of the fittest individuals. Characteristics of the evolution of such side-effects in the shadow appear to be the following: (1) The specific complex morphologies are unique (or at least very rare) among the set of de novo initiated evolutionary histories. (2) Similar morphologies are reinvented at large temporal distances during one evolutionary history and also when evolution is restarted after the main cell differentiation pattern has been established. (3) A mosaic-like evolution at the morphological level, where different morphological features occur in many combinations, while at the genotypic level recombination is not implemented and genotypes diverge linearly and at a constant rate.

Evolving mechanisms of morphogenesis: on the interplay between differential adhesion and cell differentiation.

Differential cell adhesion, mediated by e.g. integrin and cadherins/catenines, plays an important role in morphogenesis and it has been shown that there is intimate cross-talk between their expression and modification, and inter-cellular signalling, cell differentiation, cell growth and apoptosis. In this paper, we introduce and use a formal model to explore the morphogenetic potential of the interplay between these processes. We demonstrate the formation of interesting morphologies. Initiated by cell differentiation, differential cell adhesion leads to a long transient of cell migrations, e.g. engulfing and intercalation of cells and cell layers. This transient can be sustained dynamically by further cell differentiation, and by cell growth/division and cell death which are triggered by the (also long range) forces (stretching and squeezing) generated by the cell adhesion. We study the interrelation between modes of cell differentiation and modes of morphogenesis. We use an evolutionary process to zoom in on gene-regulation networks which lead to cell differentiation. Morphogenesis is not selected for but appears as a side-effect. The evolutionary dynamics shows the hallmarks of evolution on a rugged landscape, including long neutral paths. We show that a combinatorially large set of morphologies occurs in the vicinity of a neutral path which sustains cell differentiation. Thus, an almost linear molecular phylogeny gives rise to mosaic evolution on the morphological level.

Competition and dispersal in predator-prey waves.

Dispersing predators and prey can exhibit complex spatio-temporal wave-like patterns if the interactions between them cause oscillatory dynamics. We study the effect of these predator-prey density waves on the competition between prey populations and between predator populations with different dispersal strategies. We first describe 1- and 2-dimensional simulations of both discrete and continuous predator-prey models. The results suggest that any population that diffuses faster, disperses farther, or is more likely to disperse will exclude slower diffusing, shorter dispersing, or less likely dispersing populations, everything else being equal. It also appears that it does not matter whether time, space, or state are discrete or continuous, nor what the exact interactions between the predators and prey are. So long as waves exist the competition between populations occurs in a similar fashion. We derive a theory that qualitatively explains the observed behaviour and calculate approximate analytical solutions that describe, to a reasonable extent, these behaviours. Predictions about the cost of dispersal are tested. If strong enough, cost can reverse the populations' relative competitive strengths or lead to coexistence because of the effect of spiral wave cores. The theory is also able to explain previous results of simulations of coexistence in host-parasitoid models (Comins, H. N., and Massell, M. P., 1996, J. Theor. Biol. 183, 19-28).

Migration and thermotaxis of dictyostelium discoideum slugs, a model study

Dictyostelium discoideum slugs show a pronounced thermotaxis. We have modelled the motion of the D. discoideum slug in the absence and in the presence of a thermal gradient. Our model is an extension of the hybrid cellular automata/partial differential equation model, as formulated by Savill and Hogeweg [J. theor. Biol., (1997) 184, 229-235]. The modelled slugs maintain their shape and crawl, with a velocity depending on slug size, as found in experiments. Moreover, they show thermotactic behaviour: independent of the initial orientation, after some transient process, the slugs start moving along the temperature gradient. The slug behaviour in our model is due to the collective behaviour of the amoebae. Individual amoebae can neither respond to a shallow temperature gradient, nor show differentiation in motion velocity. The behaviour is achieved by a modification of the cyclic AMP waves: differences in temperature alter the excitability of the cell, and thereby the shape of the cyclic AMP wave. Chemotaxis towards cyclic AMP causes the slug to turn. We show that the mechanism still functions at very low signal-to-noise ratios. Copyright 1999 Academic Press.

Colicin diversity: a result of eco-evolutionary dynamics.

Colicins are plasmids that are carried in Escherichia coli. They code for a toxic protein and for proteins that confer on the host immunity against this toxin. When bacteria carry plasmids their growth rate is reduced. At the same time, the production of toxins makes it possible for colicinogenic bacteria to invade bacterium strains that are not immune. In natural bacterium populations there is a high diversity of colicin types. The reason for the maintenance of this diversity has been the subject of much recent debate. We have studied a simple eco-evolutionary model of the interaction of bacteria with colicins and show that high diversity of colicins is to be expected. We find two different dynamical modes each with a high diversity: a hyperimmunity mode and a multitoxicity mode. Bacteria are immune to most toxins in the first mode but in fact produce very few toxins. In the second mode bacteria are immune only to those toxins that they actually produce. In the second mode toxin levels per bacterium are much higher, whereas immunity levels per bacterium are lower.

Evolution of the immune repertoire with and without somatic DNA recombination.

Repertoire of an immune system is a set of antigen receptors each having a unique specificity to bind an antigen. In many vertebrate species, antigen receptors are produced via combinatorial arrangements of DNA segments in specialized immune cells. Due to this molecular mechanism, repertoire of vertebrate species is potentially very large. The diversity of repertoire is thought to guarantee recognition of most ill-causing micro-organisms. In vertebrate species however, similar editing of DNA segments has not been demonstrated to take place. Immune system of invertebrate species therefore seems to operate in a distinct manner from that of vertebrate species. Using an evolutionary model in which organisms struggle to fight infections, we attempt to understand why some species use a more diverse set of antigen receptors than others. Individuals in our model either use somatic DNA recombination to produce antigen receptors (as in vertebrates) or do not use such a mechanism (as in vertebrates). We found that individuals having an invertebrate-like immune system came to employ only a few antigen receptors to recognize a set of pathogens whereas those with a vertebrate-like immune system use a larger set of more specific antigen receptors to recognize the same set of pathogens. Our interpretation of this finding is that because the genetics of the immune system imposed different constraints on the evolutionary process, two distinct recognition strategies have been adapted by these species.

Spatially induced speciation prevents extinction: the evolution of dispersal distance in oscillatory predator-prey models.

In a discrete-generation, individual-oriented model of predator-prey interactions that exhibits oscillations, we show that the self-structuring of the populations into spiral waves induces a selection pressure for ever-increasing dispersal distances in both populations. As the dispersal distances increase, the sizes of the spatial patterns increase, until they are too large to fit into the limited space. The patterns are then lost and the predators go extinct. This scenario, is, however, not the only outcome. A second selection pressure induced by the spatial boundary can cause reduction of the dispersal distances. Depending on the relative strengths of the two selection pressures, the predators and prey may speciate to give coexistence between short-dispersing boundary quasi-species and far-dispersing spiral quasi-species. Now, when pattern loss occurs, the predators switch to predating on the boundary prey quasi-species and do not go extinct. Also, if the populations reproduce sexually, local gene flow can inhibit the evolution of increasing dispersal distances, and hence the spatial patterns are not lost. Speciation and coexistence can also occur in the sexually reproducing species.

Self-reinforcing spatial patterns enslave evolution in a host-parasitoid system.

Spatially structured models of host-parasitoid interactions exhibit self-structuring into spatial patterns such as spiral waves and turbulence. We discuss the consequences of these patterns in an eco-evolutionary model of host-parasitoid interactions with evolution of the parasitoids' ability to disperse towards dense populations of hosts (termed the aggregation strength). It turns out that the direction of, and the time-scale over which the evolutionary selection pressure acts depends on the type of spatial pattern a parasitoid finds itself in. Evolution tends to reinforce the existence of the prevalent local pattern. Moreover, there is also competition between the patterns that ultimately determines the eco-evolutionary attractor. It is the interaction between multiple processes across spatial and temporal scales that leads to the rich meso-scale behaviour. Predicting the evolutionary outcome from statistical measures and subprocesses is shown to give incorrect and conflicting answers. Comparison with the behaviours of the complex Ginzburg-Landau equation shows striking similarities on which we comment.

Evolutionary stagnation due to pattern-pattern interactions in a coevolutionary predator-prey model.

We consider a spatially structured model of a coevolutionary predator-prey system with interactions in a one-dimensional phenotype space. We show that in phenotype space predators and prey organize themselves into distinct clusters of phenotypes called quasi-species. The prey quasi-species also cluster in patches in real space. As the prey quasi-species evolve away from the predator quasi-species (in phenotype space) the prey patch size reduces and the single predator quasi-species is inhibited from evolving toward either of the two prey species. We show that it is the interaction between the phenotype space patterns (quasi-species) and the real space patterns (patches) that inhibit the predators from evolving.

Evolutionary consequences of coevolving targets

Most evolutionary optimization models incorporate a fitness evaluation that is based on a predefined static set of test cases or problems. In the natural evolutionary process, selection is of course not based on a static fitness evaluation. Organisms do not have to combat every existing disease during their lifespan; organisms of one species may live in different or changing environments; different species coevolve. This leads to the question of how information is integrated over many generations. This study focuses on the effects of different fitness evaluation schemes on the types of genotypes and phenotypes that evolve. The evolutionary target is a simple numerical function. The genetic representation is in the form of a program (i.e., a functional representation, as in genetic programming). Many different programs can code for the same numerical function. In other words, there is a many-to-one mapping between "genotypes" (the programs) and "phenotypes". We compare fitness evaluation based on a large static set of problems and fitness evaluation based on small coevolving sets of problems. In the latter model very little information is presented to the evolving programs regarding the evolutionary target per evolutionary time step. In other words, the fitness evaluation is very sparse. Nevertheless the model produces correct solutions to the complete evolutionary target in about half of the simulations. The complete evaluation model, on the other hand, does not find correct solutions to the target in any of the simulations. More important, we find that sparse evaluated programs are better generalizable compared to the complete evaluated programs when they are evaluated on a much denser set of problems. In addition, the two evaluation schemes lead to programs that differ with respect to mutational stability; sparse evaluated programs are less stable than complete evaluated programs.

Spatial pattern formation during aggregation of the slime mould Dictyostelium discoideum.

Stream formation and spiral wave behaviour during the aggregation of Dictyostelium discoideum (Dd) are studied in a model based on the Martiel-Goldbeter equations for cAMP relay, combined with chemotactic motion of Dd cells. The results show that stream formation occurs if the turnover rate of intracellular cAMP is increased. This increase in the turnover rate of cAMP[in] leads to a dependence of the speed of the cAMP wave on the cell density. We propose that this dependence of wave speed on cell density is the underlying mechanism for stream formation. Besides stream formation, increasing the turnover rate of cAMP[in] also results in a spiral wave period that decreases during aggregation, a phenomenon that is commonly observed in situ. Furthermore, the dependence of wave speed on cell density is measured empirically. The speed of the cAMP wave is found to decrease as the wave travels from high to low cell density. This indicates that in situ, wave speed does depend on cell density.

Pattern generation in molecular evolution: exploitation of the variation in RNA landscapes.

Evolution of RNA secondary structure is studied using simulation techniques and statistical analysis of fitness landscapes. The transition from RNA sequence to RNA secondary structure leads to fitness landscapes that have local variations in their "ruggedness." Evolution exploits these variations. In stable environments it moves the quasispecies toward relatively "flat" peaks, where not only the master sequence but also its mutants have a high fitness. In a rapidly changing environment, the situation is reversed; evolution moves the quasispecies to a region where the correlation between secondary structures of "neighboring" RNA sequences is relatively low. In selection for simple secondary structures the movement toward flat peaks leads to pattern generation in the RNA sequences. Patterns are generated at the level of polynucleotide frequencies and the distribution of purines and pyrimidines. The patterns increase the modularity of the sequence. They thereby prevent the formation of alternative secondary structures after mutations. The movement of the quasispecies toward relatively rugged parts of the landscape results in pattern generation at the level of the RNA secondary structure. The base-pairing frequency of the sequences increases. The patterns that are generated in the RNA sequences and the RNA secondary structures are not directly selected for and can be regarded as a side effect of the evolutionary dynamics of the system.