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55 results for “mutation accumulation”
An estimate of fitness reduction from mutation accumulation in a mammal allows assessment of the consequences of relaxed selection: Dataset
<p>Supplementary files (data and analysis) for "An estimate of fitness reduction from mutation accumulation in a mammal allows assessment of the consequences of relaxed selection"</p> <p>Supplementary File 1: C3H_pheno_fix_Jun7_2023_nolowmut.csv</p> <p>Data for all mice in MA experiment including: mouse ID, sire, dam, generation, mating ID, sex, weight at 3 weeks, weight at 6 weeks, tail length, litter size, litter ID, line ID</p> <p> </p> <p>Supplementary File 2: C3H_pheno_Kontrol_June2023.csv</p> <p>Data for all control mice including: mouse ID, sire, dam, generation, mating ID, sex, weight at 3 weeks, weight at 6 weeks, tail length, litter size, litter ID, line ID</p> <p> </p> <p>Supplementary File 3: C3H_birthdates.csv</p> <p>Data for all C3H mice including: mouse ID, birthdate</p> <p> </p> <p>Supplementary File 4: MA_pheno.R</p> <p>R code for visualising trait data, running linear regressions, and comparing control and MA experiment data</p> <p> </p> <p>Supplementary File 5: C3H_pheno_burnin20_Jun7_2023_nolowmut.csv</p> <p>Data for all mice in MA experiment including a 20 generation burn-in to simulate mutation-drift balance for Animal model analyses: mouse ID, sire, dam, generation, mating ID, sex, weight at 3 weeks, weight at 6 weeks, tail length, litter size, litter ID, line ID</p> <p> </p> <p>Supplementary File 6: asreml_C3H_ALL.R</p> <p>R code for estimating mutational heritabilities using mixed model analysis</p> <p> </p> <p>Supplementary File 7: C3H_ped_rekey_Jun2023.csv</p> <p>Pedigree data for all mice in MA experiment</p> <p> </p> <p>Supplementary File 8: C3H_ped_rekey_KEY.csv</p> <p>Key for pedigree data file</p> <p> </p> <p>Supplementary File 9: plot_pedigree_tree_MS_final.R</p> <p>R code for visualising pedigree of mice in MA experiment</p>
Drosophila serrata mutation accumulation lines: Phenotypic data on survival following infection with Drosophila C virus and reproduction
<p>The impact of selection on host immune function genes has been widely documented. However, it remains essentially unknown how mutation influences the quantitative immune traits that selection acts on. Applying a classical mutation accumulation (MA) experimental design in <em>Drosophila serrata</em>, we found the mutational variation in susceptibility (median time of death, LT50) to Drosophila C virus (DCV) was of similar magnitude to that reported for intrinsic survival traits. Mean LT50 did not change as mutations accumulated, suggesting no directional bias in mutational effects. Maintenance of genetic variance in immune function is hypothesised to be influenced by pleiotropic effects on immunity and other traits that contribute to fitness. To investigate this, we assayed female reproductive output for a subset of MA lines with relatively long or short survival times under DCV infection. Longer survival time tended to be associated with lower reproductive output, suggesting that mutations affecting susceptibility to DCV had pleiotropic effects on investment in reproductive fitness. Further studies are needed to uncover the general patterns of mutational effect on immune responses and other fitness traits, and to determine how selection might typically act on new mutations via their direct and pleiotropic effects.</p>
Drosophila serrata mutation accumulation lines: Phenotypic data on survival following infection with Drosophila C virus and reproduction
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Conditionally deleterious mutation load accumulates in genomic islands but can be purged with sufficient genotypic redundancy
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Fitness effects of mutations: An assessment of PROVEAN predictions using mutation accumulation data
<p><span><span><span><span>Predicting fitness in natural populations is a major challenge in biology. It may be possible to leverage fast-accumulating genomic datasets to infer the fitness effects of mutant alleles, allowing evolutionary questions to be addressed in any organism. In this paper, we investigate the utility of one such tool, called PROVEAN. This program compares a query sequence with existing data to provide an alignment-based score for any protein variant, with scores categorized as neutral or deleterious based on a preset threshold. PROVEAN has been used widely in evolutionary studies, e.g., to estimate mutation load in natural populations, but has not been formally tested as a predictor of aggregate mutational effects on fitness. Using three large, published datasets on the genome sequences of laboratory mutation accumulation lines, we assessed how well PROVEAN predicted the actual fitness patterns observed, relative to other metrics. In most cases, we find that a simple count of the total number of mutant proteins is a better predictor of fitness than the number of variants scored as deleterious by PROVEAN. We also find that the sum of all mutant protein scores explains variation in fitness better than the number of mutant proteins in one of the datasets. We discuss the implications of these results for studies of populations in the wild.</span></span></span></span></p>
A computational method for predicting the most likely evolutionary trajectories in the stepwise accumulation of resistance mutations
<p>Supporting information dataset for <em>A computational method for predicting the most likely evolutionary trajectories in the stepwise accumulation of resistance mutations, </em>including Flex ddG binding free energy predictions, epistasis calculations, pathway probabilities, Rosetta files and structural files. </p>
Fitness effects of mutations: An assessment of PROVEAN predictions using mutation accumulation data
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French (F) and Swedish (S) Founder (P) and Mutation Accumulation Line (MA) performance in France and Sweden
<p>Little is empirically known about the contribution of mutations to fitness in natural environments. However, Fisher's Geometric Model (FGM) provides a conceptual foundation to consider the influence of the environment on mutational effects. To quantify mutational properties in the field, we established eight sets of MA lines (7-10 generations) derived from eight founders collected from natural populations of <i>Arabidopsis thaliana</i> from French and Swedish sites, representing the range margins of the species in Europe. We reciprocally planted the MA lines and their founders at French and Swedish sites, allowing us to test predictions of FGM under naturally occurring environmental conditions. The performance of the MA lines relative to each other and to their respective founders confirmed some and contradicted other predictions of the FGM: the contribution of mutation to fitness variance increased when the genotype was in an environment where its fitness was low, i.e., in the away environment, but mutations were more likely to be beneficial when the genotype was in its home environment. Consequently, environmental context plays a large role in the contribution of mutations to evolutionary process and local adaptation does not guarantee that a genotype is at or close to its optimum.</p>
Data from: The accumulation of deleterious mutations as a consequence of domestication and improvement in sunflowers and other Compositae crops
For populations to maintain optimal fitness, harmful mutations must be efficiently purged from the genome. Yet, under circumstances that diminish the effectiveness of natural selection, such as the process of plant and animal domestication, deleterious mutations are predicted to accumulate. Here, we compared the load of deleterious mutations in 21 accessions from natural populations and 19 domesticated accessions of the common sunflower using whole-transcriptome single nucleotide polymorphism data. Although we find that genetic diversity has been greatly reduced during domestication, the remaining mutations were disproportionally biased toward nonsynonymous substitutions. Bioinformatically predicted deleterious mutations affecting protein function were especially strongly over-represented. We also identify similar patterns in two other domesticated species of the sunflower family (globe artichoke and cardoon), indicating that this phenomenon is not due to idiosyncrasies of sunflower domestication or the sunflower genome. Finally, we provide unequivocal evidence that deleterious mutations accumulate in low recombining regions of the genome, due to the reduced efficacy of purifying selection. These results represent a conundrum for crop improvement efforts. Although the elimination of harmful mutations should be a long-term goal of plant and animal breeding programs, it will be difficult to weed them out because of limited recombination.
Data from: Do genetic drift and accumulation of deleterious mutations preclude adaptation? Empirical investigation using RADseq in a northern lacustrine fish
Understanding genomic signatures of divergent selection underlying long-term adaptation in populations located in heterogeneous environments is a key goal in evolutionary biology. In this study, we investigated neutral, adaptive and deleterious genetic variation using 7,192 SNPs in 31 Lake Trout (Salvelinus namaycush) populations (n = 673) from Québec, Canada. Average genetic diversity was low, weakly shared among lakes, and positively correlated to lake size, indicating a major role for genetic drift subsequent to lake isolation. Putatively deleterious mutations were on average at lower frequencies than the other SNPs, and their abundance relative to the entire polymorphism in each population was positively correlated to inbreeding, suggesting that the effectiveness of purifying selection was negatively correlated to inbreeding, as predicted from theory. Despite evidence for pronounced genetic drift and inbreeding, several outlier loci were associated with temperature and found in or close to genes with biologically relevant functions notably related to heat-stress and immune responses. Outcomes of gene-temperature associations were influenced by the inclusion of the most inbred populations, in which allele frequencies deviated the most from model predictions. This result illustrates challenge in identifying gene-environment associations in cases of high genetic drift and restricted gene flow and suggests limited adaptation in populations experiencing higher inbreeding. We discuss the relevance of these findings for the conservation and management, notably regarding stocking and genetic rescue, of Lake Trout populations and other species inhabiting highly fragmented habitats.
Accumulation of deleterious mutations in landlocked threespine stickleback populations
<p></p><p>Colonization of new habitats often reduces population sizes and may result in the accumulation of deleterious mutations by genetic drift. Compared to the genomic basis for adaptation to new environments, genome-wide analysis of deleterious mutations in isolated populations remains limited. In the present study, we investigated the accumulation of deleterious mutations in five endangered freshwater populations of threespine stickleback (Gasterosteus aculeatus) in the central part of the mainland of Japan. Using whole genome resequencing data, we first conducted phylogenomic analysis and confirmed at least two independent freshwater colonization events in the central mainland from ancestral marine ecotypes. Next, analyses of single nucleotide polymorphisms (SNPs) showed a substantial reduction of heterozygosity in freshwater populations compared to marine populations. Reduction in heterozygosity was more apparent at the center of each chromosome than the peripheries and on X-chromosomes compared to autosomes. Third, bioinformatic analysis of deleterious mutations showed increased accumulation of putatively deleterious mutations in the landlocked freshwater populations compared to marine populations. For the majority of populations examined, the frequencies of putatively deleterious mutations were higher on X-chromosomes than on autosomes. The inter-population comparison indicated that the majority of putatively deleterious mutations may have accumulated independently. Thus, whole genome resequencing of endangered populations can help to estimate the accumulation of deleterious mutations and inform us of which populations are the most severely endangered. Furthermore, analysis of variation among chromosomes can give insights into whether any particular chromosomes are likely to accumulate deleterious mutations.</p><p></p>
Data from: Selection bias in mutation accumulation
<p>Mutation accumulation (MA) experiments, in which de novo mutations are sampled and subsequently characterized, are an essential tool in understanding the processes underlying evolution. In microbial populations, MA protocols typically involve a period of population growth between severe bottlenecks, such that a single individual can form a visible colony. While it has long been appreciated that the action of positive selection during this growth phase cannot be eliminated, it is typically assumed to be negligible. Here, we quantify the effect of both positive and negative selection in MA studies, demonstrating that selective effects can substantially bias the distribution of fitness effects (DFE) and mutation rates estimated from typical MA protocols in microbes. We then present a simple correction for this bias which applies to both beneficial and deleterious mutations, and can be used to correct the observed DFE in multiple environments. We use simulated MA experiments to illustrate the extent to which the MA-inferred DFE differs from the underlying true DFE, and demonstrate that the proposed correction accurately reconstructs the true DFE over a wide range of scenarios; we also provide an example of these corrections applied to experimental data. These results highlight that positive selection during microbial MA experiments is in fact not negligible, but can be corrected to gain a more accurate understanding of fundamental evolutionary parameters.</p>
FIG. 1 in OPINION Testing for the accumulation of deleterious mutations in asexual eukaryote genomes using molecular sequences
FIG. 1. Phylogeny of representative sexual and asexual Lachnidae with estimates of the numbers of replacement and silent substitutions for EF1a and CO2 on each branch. See text for description of estimation of the numbers of substitutions in each category. Phylogeny is from Normark (2000).
French (F) and Swedish (S) Founder (P) and Mutation Accumulation Line (MA) performance in France and Sweden
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Data from: Do genetic drift and accumulation of deleterious mutations preclude adaptation? Empirical investigation using RADseq in a northern lacustrine fish
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Data from: The accumulation of deleterious mutations as a consequence of domestication and improvement in sunflowers and other Compositae crops
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Data from: Fitness decline under osmotic stress in Caenorhabditis elegans populations subjected to spontaneous mutation accumulation at varying population sizes
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Accumulation of deleterious mutations in landlocked threespine stickleback populations
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Data from: Selection bias in mutation accumulation
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Data from: Fitness of Arabidopsis thaliana mutation accumulation lines whose spontaneous mutations are known
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