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.
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 workshop's talks, and identify the main themes that emerged from the open discussions. Two important conclusions from the discussions are: (1) the idea of
about OEE—it seems clear that there is more than one interesting and important kind of OEE; and (2) the importance of distinguishing observable
of systems undergoing OEE from hypothesized
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
.
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.
•Successful populations originate from rugged areas close to high-fertility lands.•We use simulations and geographical data to show this relationship objectively.•Our analysis predicts places where ...successful populations may have originated from.
In order to understand the dynamics of emergence and spreading of socio-technical innovations and population moves it is important to determine the place of origin of these populations. Here we focus on the role of geographical factors, such as land fertility and mountains in the context of human population evolution and distribution dynamics. We use a constrained diffusion-based computational model, computer simulations and the analysis of geographical and land-quality data. Our analysis shows that successful human populations, i.e. those which become dominant in their socio – geographical environment, originate from lands of many valleys with relatively low land fertility, which are close to areas of high land fertility. Many of the homelands predicted by our analysis match the assumed homelands of known successful populations (e.g. Bantus, Turkic, Maya). We also predict other likely homelands as well, where further archaeological, linguistic or genetic exploration may confirm the place of origin for populations with no currently identified urheimat. Our work is significant because it advances the understanding of human population dynamics by guiding the identification of the origin locations of successful populations.
In Evolutionary Robotics, Lexicase selection has proven effective when a single task is broken down into many individual parameterizations. Evolved individuals have generalized across unique ...configurations of an overarching task. Here, we investigate the ability of Lexicase selection to generalize across multiple tasks, with each task again broken down into many instances. There are three objectives: to determine the feasibility of introducing additional tasks to the existing platform; to investigate any consequential effects of introducing these additional tasks during evolutionary adaptation; and to explore whether the schedule of presentation of the additional tasks over evolutionary time affects the final outcome. To address these aims we use a quadruped animat controlled by a feed-forward neural network with joint-angle, bearing-to-target, and spontaneous sinusoidal inputs. Weights in this network are trained using evolution with Lexicase-based parent selection. Simultaneous adaptation in a wall crossing task (labelled
) is explored when one of two different alternative tasks is also present:
or
. Each task is parameterized into 100 distinct variants, and these variants are used as environments for evaluation and selection with Lexicase. We use performance in a single-task
environment as a baseline against which to examine the multi-task configurations. In addition, the objective sampling strategy (the manner in which tasks are presented over evolutionary time) is varied, and so data for treatments implementing uniform sampling, even sampling, or degrees of generational sampling are also presented. The Lexicase mechanism successfully integrates evolution of both
and
with
, though there is a performance penalty compared to single task evolution. The size of the penalty depends on the similarity of the tasks. Complementary tasks (
/
) show better performance than antagonistic tasks (
/
). In complementary tasks performance is not affected by the sampling strategy. Where tasks are antagonistic, uniform and even sampling strategies yield significantly better performance than generational sampling. In all cases the generational sampling requires more evaluations and consequently more computational resources. The results indicate that Lexicase is a viable mechanism for multitask evolution of animat neurocontrollers, though the degree of interference between tasks is a key consideration. The results also support the conclusion that the naive, uniform random sampling strategy is the best choice when considering final task performance, simplicity of implementation, and computational efficiency.
Malaria 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.
We 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.
Our 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.
There have been numerous attempts to develop 3D virtual agents by applying evolutionary processes to populations that exist in a realistic physical simulation. Whilst often contributing useful ...knowledge, no previous work has demonstrated the capacity to evolve a sequence of increasingly complex behaviours in a single, unified system. This thesis has this demonstration as its primary aim. A rigorous exploration of one aspect of incremental artificial evolution was carried out to understand how subtask presentations affect the whole-task generalisation performance of evolved, fixed-morphology 3D agents. Results from this work led to the design of an environment–body–control architecture that can be used as a base for evolving multiple behaviours incrementally. A simulation based on this architecture with a more complex environment was then developed and explored. This system was then adapted to include elements of physical manipulation as a first step toward a fully physical virtual creature environment demonstrating advanced evolved behaviours. The thesis demonstrates that incremental evolutionary systems can be subject to problems of forgetting and loss of gradient, and that different complexification strategies have a strong bearing on the management of these issues. Presenting successive generations of the population to a full range of objective functions (covering and revisiting the range of complexity) outperforms straightforward linear or direct presentations, establishing a more robust approach to the evolution of naturalistic embodied agents. When combining this approach with a bespoke control architecture in a problem requiring reactive and deliberative behaviours, we see results that not only demonstrate success at the tasks, but also show a variety of intricate behaviours being used. This is the first ever example of the simultaneous incremental evolution in 3D of composite behaviours more complex than simple locomotion. Finally, the architecture demonstrably supports extension to manipulation in a feedback control task. Given the problem-agnostic controller architecture, these results indicate a system with potential for discovering yet more advanced behaviours in yet more complex environments.
There have been numerous attempts to develop 3D virtual agents by applying evolutionary processes to populations that exist in a realistic physical simulation. Whilst often contributing useful ...knowledge, no previous work has demonstrated the capacity to evolve a sequence of increasingly complex behaviours in a single, unified system. This thesis has this demonstration as its primary aim. A rigorous exploration of one aspect of incremental artificial evolution was carried out to understand how subtask presentations affect the whole-task generalisation performance of evolved, fixed-morphology 3D agents. Results from this work led to the design of an environment–body–control architecture that can be used as a base for evolving multiple behaviours incrementally. A simulation based on this architecture with a more complex environment was then developed and explored. This system was then adapted to include elements of physical manipulation as a first step toward a fully physical virtual creature environment demonstrating advanced evolved behaviours. The thesis demonstrates that incremental evolutionary systems can be subject to problems of forgetting and loss of gradient, and that different complexification strategies have a strong bearing on the management of these issues. Presenting successive generations of the population to a full range of objective functions (covering and revisiting the range of complexity) outperforms straightforward linear or direct presentations, establishing a more robust approach to the evolution of naturalistic embodied agents. When combining this approach with a bespoke control architecture in a problem requiring reactive and deliberative behaviours, we see results that not only demonstrate success at the tasks, but also show a variety of intricate behaviours being used. This is the first ever example of the simultaneous incremental evolution in 3D of composite behaviours more complex than simple locomotion. Finally, the architecture demonstrably supports extension to manipulation in a feedback control task. Given the problem-agnostic controller architecture, these results indicate a system with potential for discovering yet more advanced behaviours in yet more complex environments.
During the course of any sporting event, critical cognitive and physical tasks are performed within a dynamic, complex, collaborative system comprising multiple humans and artifacts, under ...pressurized, complex, and rapidly changing conditions. Highly skilled, well-trained individuals walk a fine line between task success and failure, with only slig
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