Self-adaptation of Mutation Rates in Non-elitist Populations

The runtime of evolutionary algorithms (EAs) depends critically on their parameter settings, which are often problem-specific. Automated schemes for parameter tuning have been developed to alleviate the high costs of manual parameter tuning. Experimental results indicate that self-adaptation, where parameter settings are encoded in the genomes of individuals, can be effective in continuous optimisation. However, results in discrete optimisation have been less conclusive. Furthermore, a rigorous runtime analysis that explains how self-adaptation can lead to asymptotic speedups has been missing. This paper provides the first such analysis for discrete, population-based EAs. We apply level-based analysis to show how a self-adaptive EA is capable of fine-tuning its mutation rate, leading to exponential speedups over EAs using fixed mutation rates.Comment: To appear in the Proceedings of the 14th International Conference on Parallel Problem Solving from Nature (PPSN

Interplay between pleiotropy and secondary selection determines rise and fall of mutators in stress response

Dramatic rise of mutators has been found to accompany adaptation of bacteria in response to many kinds of stress. Two views on the evolutionary origin of this phenomenon emerged: the pleiotropic hypothesis positing that it is a byproduct of environmental stress or other specific stress response mechanisms and the second order selection which states that mutators hitchhike to fixation with unrelated beneficial alleles. Conventional population genetics models could not fully resolve this controversy because they are based on certain assumptions about fitness landscape. Here we address this problem using a microscopic multiscale model, which couples physically realistic molecular descriptions of proteins and their interactions with population genetics of carrier organisms without assuming any a priori fitness landscape. We found that both pleiotropy and second order selection play a crucial role at different stages of adaptation: the supply of mutators is provided through destabilization of error correction complexes or fluctuations of production levels of prototypic mismatch repair proteins (pleiotropic effects), while rise and fixation of mutators occur when there is a sufficient supply of beneficial mutations in replication-controlling genes. This general mechanism assures a robust and reliable adaptation of organisms to unforeseen challenges. This study highlights physical principles underlying physical biological mechanisms of stress response and adaptation

The Distribution of Fitness Effects of Beneficial Mutations in Pseudomonas aeruginosa

Understanding how beneficial mutations affect fitness is crucial to our understanding of adaptation by natural selection. Here, using adaptation to the antibiotic rifampicin in the opportunistic pathogen Pseudomonas aeruginosa as a model system, we investigate the underlying distribution of fitness effects of beneficial mutations on which natural selection acts. Consistent with theory, the effects of beneficial mutations are exponentially distributed where the fitness of the wild type is moderate to high. However, when the fitness of the wild type is low, the data no longer follow an exponential distribution, because many beneficial mutations have large effects on fitness. There is no existing population genetic theory to explain this bias towards mutations of large effects, but it can be readily explained by the underlying biochemistry of rifampicin–RNA polymerase interactions. These results demonstrate the limitations of current population genetic theory for predicting adaptation to severe sources of stress, such as antibiotics, and they highlight the utility of integrating statistical and biophysical approaches to adaptation

Mutator dynamics in sexual and asexual experimental populations of yeast

<p>Abstract</p> <p>Background</p> <p>In asexual populations, mutators may be expected to hitchhike with associated beneficial mutations. In sexual populations, recombination is predicted to erode such associations, inhibiting mutator hitchhiking. To investigate the effect of recombination on mutators experimentally, we compared the frequency dynamics of a mutator allele (<it>msh2</it>Δ) in sexual and asexual populations of <it>Saccharomyces cerevisiae</it>.</p> <p>Results</p> <p>Mutator strains increased in frequency at the expense of wild-type strains in all asexual diploid populations, with some approaching fixation in 150 generations of propagation. Over the same period of time, mutators declined toward loss in all corresponding sexual diploid populations as well as in haploid populations propagated asexually.</p> <p>Conclusions</p> <p>We report the first experimental investigation of mutator dynamics in sexual populations. We show that a strong mutator quickly declines in sexual populations while hitchhiking to high frequency in asexual diploid populations, as predicted by theory. We also show that the <it>msh2Δ </it>mutator has a high and immediate realized cost that is alone sufficient to explain its decline in sexual populations. We postulate that this cost is indirect; namely, that it is due to a very high rate of recessive lethal or strongly deleterious mutation. However, we cannot rule out the possibility that <it>msh2</it>Δ also has unknown directly deleterious effects on fitness, and that these effects may differ between haploid asexual and sexual populations. Despite these reservations, our results prompt us to speculate that the short-term cost of highly deleterious recessive mutations can be as important as recombination in preventing mutator hitchhiking in sexual populations.</p

No evidence for association between polymorphisms in GRM3 and schizophrenia

BACKGROUND: Three studies have previously reported data that were interpreted by the authors as supportive of association between schizophrenia and polymorphisms in the gene encoding the metabotropic glutamate receptor GRM3. METHODS: In a bid to examine this hypothesis, we examined seven SNPs spanning GRM3 in a UK case-control sample (schizophrenic cases n = 674, controls n = 716). These included all SNPs previously reported to be associated, alone or in haplotypes, with schizophrenia in European or European American samples. RESULTS: Our data showed no evidence for association with single markers, or 2, 3, 4 and 5 marker haplotypes, nor did any specific haplotypes show evidence for association according to previously observed patterns. CONCLUSION: Examination of our own data and those of other groups leads us to conclude that at present, GRM3 should not be viewed as a gene for which there is replicated evidence for association with schizophrenia

Horizontal gene transfer dynamics and distribution of fitness effects during microbial in silico evolution

<p>Abstract</p> <p>Background</p> <p>Horizontal gene transfer (HGT) is a process that facilitates the transfer of genetic material between organisms that are not directly related, and thus can affect both the rate of evolution and emergence of traits. Recent phylogenetic studies reveal HGT events are likely ubiquitous in the Tree of Life. However, our knowledge of HGT's role in evolution and biological organization is very limited, mainly due to the lack of ancestral evolutionary signatures and the difficulty to observe complex evolutionary dynamics in a laboratory setting. Here, we utilize a multi-scale microbial evolution model to comprehensively study the effect of HGT on the evolution of complex traits and organization of gene regulatory networks.</p> <p>Results</p> <p>Large-scale simulations reveal a distinct signature of the Distribution of Fitness Effect (DFE) for HGT events: during evolution, while mutation fitness effects become more negative and neutral, HGT events result in a balanced effect distribution. In either case, lethal events are significantly decreased during evolution (33.0% to 3.2%), a clear indication of mutational robustness. Interestingly, evolution was accelerated when populations were exposed to correlated environments of increasing complexity, especially in the presence of HGT, a phenomenon that warrants further investigation. High HGT rates were found to be disruptive, while the average transferred fragment size was linked to functional module size in the underlying biological network. Network analysis reveals that HGT results in larger regulatory networks, but with the same sparsity level as those evolved in its absence. Observed phenotypic variability and co-existing solutions were traced to individual gain/loss of function events, while subsequent re-wiring after fragment integration was necessary for complex traits to emerge.</p

Analysis of genetic systems using experimental evolution and whole-genome sequencing

The application of whole-genome sequencing to the study of microbial evolution promises to reveal the complex functional networks of mutations that underlie adaptation. A recent study of parallel evolution in populations of Escherichia coli shows how adaptation involves both functional changes to specific proteins as well as global changes in regulation

Natural Selection Fails to Optimize Mutation Rates for Long-Term Adaptation on Rugged Fitness Landscapes

The rate of mutation is central to evolution. Mutations are required for adaptation, yet most mutations with phenotypic effects are deleterious. As a consequence, the mutation rate that maximizes adaptation will be some intermediate value. Here, we used digital organisms to investigate the ability of natural selection to adjust and optimize mutation rates. We assessed the optimal mutation rate by empirically determining what mutation rate produced the highest rate of adaptation. Then, we allowed mutation rates to evolve, and we evaluated the proximity to the optimum. Although we chose conditions favorable for mutation rate optimization, the evolved rates were invariably far below the optimum across a wide range of experimental parameter settings. We hypothesized that the reason that mutation rates evolved to be suboptimal was the ruggedness of fitness landscapes. To test this hypothesis, we created a simplified landscape without any fitness valleys and found that, in such conditions, populations evolved near-optimal mutation rates. In contrast, when fitness valleys were added to this simple landscape, the ability of evolving populations to find the optimal mutation rate was lost. We conclude that rugged fitness landscapes can prevent the evolution of mutation rates that are optimal for long-term adaptation. This finding has important implications for applied evolutionary research in both biological and computational realms

Learning to Eat Vegetables in Early Life: The Role of Timing, Age and Individual Eating Traits

Vegetable intake is generally low among children, who appear to be especially fussy during the pre-school years. Repeated exposure is known to enhance intake of a novel vegetable in early life but individual differences in response to familiarisation have emerged from recent studies. In order to understand the factors which predict different responses to repeated exposure, data from the same experiment conducted in three groups of children from three countries (n = 332) aged 4–38 m (18.9±9.9 m) were combined and modelled. During the intervention period each child was given between 5 and 10 exposures to a novel vegetable (artichoke puree) in one of three versions (basic, sweet or added energy). Intake of basic artichoke puree was measured both before and after the exposure period. Overall, younger children consumed more artichoke than older children. Four distinct patterns of eating behaviour during the exposure period were defined. Most children were “learners” (40%) who increased intake over time. 21% consumed more than 75% of what was offered each time and were labelled “plate-clearers”. 16% were considered “non-eaters” eating less than 10 g by the 5th exposure and the remainder were classified as “others” (23%) since their pattern was highly variable. Age was a significant predictor of eating pattern, with older pre-school children more likely to be non-eaters. Plate-clearers had higher enjoyment of food and lower satiety responsiveness than non-eaters who scored highest on food fussiness. Children in the added energy condition showed the smallest change in intake over time, compared to those in the basic or sweetened artichoke condition. Clearly whilst repeated exposure familiarises children with a novel food, alternative strategies that focus on encouraging initial tastes of the target food might be needed for the fussier and older pre-school children