BackgroundMalaria parasites of the genus Plasmodium possess large hyper-variable families of antigen-encoding genes. These are often variantly-expressed and are major virulence factors for immune evasion and the maintenance of chronic infections. Recombination and diversification of these gene families occurs readily, and may be promoted by G-quadruplex (G4) DNA motifs within and close to the variant genes. G4s have been shown to cause replication fork stalling, DNA breakage and recombination in model systems, but these motifs remain largely unstudied in Plasmodium.ResultsWe examined the nature and distribution of putative G4-forming sequences in multiple Plasmodium genomes, finding that their co-distribution with variant gene families is conserved across different Plasmodium species that have different types of variant gene families. In P. falciparum, where a large set of recombination events that occurred over time in cultured parasites has been mapped, we found a strong spatial association between these recombination events and putative G4-forming sequences. Finally, we searched Plasmodium genomes for the three classes of helicase that can unwind G4s: Plasmodium spp. have no identifiable homologue of the highly efficient G4 helicase PIF1, but they do encode two putative RecQ helicases and one homologue of the RAD3-family helicase FANCJ.ConclusionsOur analyses, conducted at the whole-genome level in multiple species of Plasmodium, support the concept that G4s are likely to be involved in recombination and diversification of antigen-encoding gene families in this important protozoan pathogen.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3183-3) contains supplementary material, which is available to authorized users.
We describe the content and outcomes of the First Workshop on Open-Ended Evolution: Recent Progress and Future Milestones (OEE1), held during the ECAL 2015 conference at the University of York, UK, in July 2015. We briefly summarize the content of the workshopʼs talks, and identify the main themes that emerged from the open discussions. Two important conclusions from the discussions are: (1) the idea of pluralism about OEE-it seems clear that there is more than one interesting and important kind of OEE; and (2) the importance of distinguishing observable behavioral hallmarks of systems undergoing OEE from hypothesized underlying mechanisms that explain why a system exhibits those hallmarks. We summarize the different hallmarks and mechanisms discussed during the workshop, and list the specific systems that were highlighted with respect to particular hallmarks and mechanisms. We conclude by identifying some of the most important open research questions about OEE that are apparent in light of the discussions. The York workshop provides a foundation for a follow-up OEE2 workshop taking place at the ALIFE XV conference in Cancún, Mexico, in July 2016. Additional materials from the York workshop, including talk abstracts, presentation slides, and videos of each talk, are available at http://alife.org/ws/oee1.
The malaria parasite Plasmodium falciparum has evolved an unusual genome structure. The majority of the genome is relatively stable, with mutation rates similar to most eukaryotic species. However, some regions are very unstable with high recombination rates, driving the generation of new immune evasion-associated var genes. The molecular factors controlling the inconsistent stability of this genome are not known. Here we studied the roles of the two putative RecQ helicases in P. falciparum, PfBLM and PfWRN. When PfWRN was knocked down, recombination rates increased four-fold, generating chromosomal abnormalities, a high rate of chimeric var genes and many microindels, particularly in known ‘fragile sites’. This is the first identification of a gene involved in suppressing recombination and maintaining genome stability in Plasmodium. By contrast, no change in mutation rate appeared when the second RecQ helicase, PfBLM, was mutated. At the transcriptional level, however, both helicases evidently modulate the transcription of large cohorts of genes, with several hundred genes—including a large proportion of vars—showing deregulated expression in each RecQ mutant. Aberrant processing of stalled replication forks is a possible mechanism underlying elevated mutation rates and this was assessed by measuring DNA replication dynamics in the RecQ mutant lines. Replication forks moved slowly and stalled at elevated rates in both mutants, confirming that RecQ helicases are required for efficient DNA replication. Overall, this work identifies the Plasmodium RecQ helicases as major players in DNA replication, antigenic diversification and genome stability in the most lethal human malaria parasite, with important implications for genome evolution in this pathogen.
The presence of bottlenecks in the transmission cycle of many RNA viruses leads to a severe reduction of number of virus particles and this occurs multiple times throughout the viral transmission cycle. Viral replication is then necessary for regeneration of a diverse mutant swarm. It is now understood that any perturbation of the mutation frequency either by increasing or decreasing the accumulation of mutations in an RNA virus results in attenuation of the virus. To determine if altering the rate at which a virus accumulates mutations decreases the probability of a successful virus infection due to issues traversing host bottlenecks, a series of mutations in the RNA-dependent RNA polymerase of Venezuelan equine encephalitis virus (VEEV), strain 68U201, were tested for mutation rate changes. All RdRp mutants were attenuated in both the mosquito and vertebrate hosts, while showing no attenuation during in vitro infections. The rescued viruses containing these mutations showed some evidence of change in fidelity, but the phenotype was not sustained following passaging. However, these mutants did exhibit changes in the frequency of specific types of mutations. Using a model of mutation production, these changes were shown to decrease the number of stop codons generated during virus replication. This suggests that the observed mutant attenuation in vivo may be due to an increase in the number of unfit genomes, which may be normally selected against by the accumulation of stop codons. Lastly, the ability of these attenuated viruses to transition through a bottleneck in vivo was measured using marked virus clones. The attenuated viruses showed an overall reduction in the number of marked clones for both the mosquito and vertebrate hosts, as well as a reduced ability to overcome the known bottlenecks in the mosquito. This study demonstrates that any perturbation of the optimal mutation frequency whether through changes in fidelity or by alterations in the mutation frequency of specific nucleotides, has significant deleterious effects on the virus, especially in the presence of host bottlenecks.
Evolving robust behaviors for robots has proven to be a challenging problem. Determining how to optimize behavior for a specific instance, while also realizing behaviors that generalize to variations on the problem often requires highly customized algorithms and problem-specific tuning of the evolutionary platform. Algorithms that can realize robust, generalized behavior without this customization are therefore highly desirable. In this paper, we examine the Lexicase selection algorithm as a possible general algorithm for a wall crossing robot task. Previous work has resulted in specialized strategies to evolve robust behaviors for this task. Here, we show that Lexicase selection is not only competitive with these strategies but after parameter tuning, actually exceeds the performance of the specialized algorithms.
The evolution of naturalistic, embodied agents and behaviours has been a long-standing goal of Artificial Life since the initial, impressive work of Karl Sims. Incremental evolution has been used extensively to improve the quality of evolutionary search in many complex, non-linear problem spaces. This work sets out to disambiguate the lexicon around incremental evolution, advocating the term environmental complexification to represent the complexification of the problem domain. We then go on to analyse various complexification strategies in a structured, complexifiable and yet simple environment: a 3D agent-based obstacle task. We divide the strategies conceptually into homogeneous and heterogeneous; homogeneous strategies expose successive generations of the population to a single or tightly clustered range of objective functions while heterogeneous strategies present many, covering the range of complexity. It was found that widely-used homogeneous complexification techniques, for example direct presentation of difficult tasks or linearly-increased difficulty, fail due to either loss-ofgradient or temporally-local over-fitting (analogous to catastrophic forgetting in neural systems). Heterogeneous methods of complexification (including oscillatory strategies) that eliminate these issues are devised and tested. The heterogeneous category outperforms the homogeneous in all metrics, establishing a much more robust approach to the evolution of naturalistic embodied agents.
Following earlier work on the neuroevolution of deliberative behaviour to solve increasingly challenging tasks in a twodimensional dynamic world, this paper presents the results of extending the original system to a three-dimensional rigid body simulation. The 3D physically based setting requires that a successful agent continually and deliberately adjust its gait, turning and other motor control over the many stages and sub-stages of these tasks, within its individual evaluation. Achieving such complex interplay between motor control and deliberative control, within a neuroevolutionary framework, is the focus of this work. To this end, a novel neural architecture is presented and an incremental evolutionary approach used to bootstrap the locomotive behaviour of the agents. Agent morphology is fixed as a quadruped with three degrees of freedom per limb. Agent populations have no initial knowledge of the problem domain, and evolve to move around and then solve progressively more difficult challenges in the environment using a tournament-based co-evolutionary algorithm. The results demonstrate not only success at the tasks but also a variety of intricate lifelike behaviours being used, separately and in combination, to achieve this success. Given the problem-agnostic controller architecture, these results indicate a potential for discovering yet more advanced behaviours in yet more complex environments.
This paper investigates the hypothesis that noise in the genotype-phenotype mapping, here called stochastic ontogenesis (SO), is an important consideration in Evolutionary Robotics. This is examined in two ways: first, in the context of seeking to generalise controller performance in an incremental task domain in simulation, and second, in a preliminary study of its effectiveness as a mechanism for crossing the "reality gap" from simulation to physical robots. The performance of evolved neurocontrollers for a fixed-morphology simulated robot is evaluated in both the presence and absence of ontogenic noise, in a task requiring the development of a walking gait that accommodates a varying environment. When SO is applied, evolution of controllers is more effective (replicates achieve higher fitness) and more robust (fewer replicates fail) than evolution using a deterministic mapping. This result is found in a variety of incremental scenarios. For the preliminary study of the utility of SO for moving between simulation and reality, the capacity of evolved controllers to handle unforeseen environmental noise is tested by introducing a stochastic coefficient of friction and evaluating previous populations in the new problem domain. Controllers evolved with deterministic ontogenesis fail to accommodate the new source of noise and show reduced fitness. In contrast, those which experienced ontogenic noise during evolution are not significantly disrupted by the additional noise in the environment. It is argued that SO is a catch-all mechanism for increasing performance of Evolutionary Robotics designs and may have further more general implications for Evolutionary Computation.
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