Mutation accumulation in a selfing population: consequences of different mutation rates between selfers and outcrossers.
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ABSTRACT:
SUBMITTER: Nakayama S
PROVIDER: S-EPMC3308984 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:We present a Bayesian method for characterizing the mating system of populations reproducing through a mixture of self-fertilization and random outcrossing. Our method uses patterns of genetic variation across the genome as a basis for inference about reproduction under pure hermaphroditism, gynodioecy, and a model developed to describe the self-fertilizing killifish Kryptolebias marmoratus. We extend the standard coalescence model to accommodate these mating systems, accounting explicitly for multilocus identity disequilibrium, inbreeding depression, and variation in fertility among mating types. We incorporate the Ewens sampling formula (ESF) under the infinite-alleles model of mutation to obtain a novel expression for the likelihood of mating system parameters. Our Markov chain Monte Carlo (MCMC) algorithm assigns locus-specific mutation rates, drawn from a common mutation rate distribution that is itself estimated from the data using a Dirichlet process prior model. Our sampler is designed to accommodate additional information, including observations pertaining to the sex ratio, the intensity of inbreeding depression, and other aspects of reproduction. It can provide joint posterior distributions for the population-wide proportion of uniparental individuals, locus-specific mutation rates, and the number of generations since the most recent outcrossing event for each sampled individual. Further, estimation of all basic parameters of a given model permits estimation of functions of those parameters, including the proportion of the gene pool contributed by each sex and relative effective numbers.
| S-EPMC4649643 | biostudies-literature
Project description:Inbreeding depression, that is the decrease in fitness of inbred relative to outbred individuals, was shown to increase strongly as life expectancy increases in plants. Because plants are thought to not have a separated germline, it was proposed that this pattern could be generated by somatic mutations accumulating during growth, since larger and more long-lived species have more opportunities for mutations to accumulate. A key determinant of the role of somatic mutations is the rate at which they occur, which probably differs between species because mutation rates may evolve differently in species with constrasting life histories. In this paper, I study the evolution of the mutation rates in plants, and consider the population-level consequences of inheritable somatic mutations given this evolution. I show that despite substantially lower somatic and meiotic mutation rates, more long-lived species still tend to accumulate larger amounts of deleterious mutations because of the increased number of opportunities they have to acquire mutations during growth, leading to higher levels of inbreeding depression in these species. However, the magnitude of this increase depends strongly on how mutagenic meiosis is relative to growth, to the point of being close to non-existent in some situations.
| S-EPMC8424331 | biostudies-literature
Project description:Until recently, the two predominant ways to estimate mutation rates were the specific-locus method and the mutation-accumulation (Bateman-Mukai) method. Both involve seeding a number of parallel lines from a small, genetically uniform population, growing as long as is feasible but not so long as to allow selection to perturb mutant frequencies, and sometimes using extreme bottlenecks to facilitate the retention of deleterious mutations. In the specific-locus method, mutations are selected according to their specific phenotypes and are confirmed by sequencing. In older versions of the mutation-accumulation method, the increase in variance of a quantitative fitness trait is measured and converted into a mutation rate. More recently, a variation on the mutation-accumulation method has become possible based on phenotype-blind genomic sequencing, which might (or might not) provide improved sampling breadth, usually at the expense of sample size. In a recent study, genomic sequencing was applied to Escherichia coli lines propagated for 40,000 generations and passaged daily via 5,000,000 cells. To mitigate the impact of selection, the only targets employed for rate calculations were putatively neutral synonymous mutations. The mutation rate estimate was about 6-fold lower than obtained previously with a robust specific-locus method. Here I argue that purifying selection acting to shape the strong codon preferences of E. coli is the probable cause of the lower estimate, rather than, for instance, a lower mutation rate in nature than in the laboratory.
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Project description:Plant mating system determines, to a great extent, the demographic and genetic properties of populations, hence their potential for adaptive evolution. Variation in plant mating system has been documented between phylogenetically related species as well between populations of a species. A common evolutionary transition, from outcrossing to selfing, is likely to occur under environmental spatial variation in the service of pollinators. Here, we studied two phenotypically (in floral traits) and genetically (in neutral molecular markers) differentiated populations of the annual, insect-pollinated, plant Datura inoxia in Mexico, that differ in the service of pollinators (Mapimí and Cañada Moreno). First, we determined the populations' parameters of phenotypic in herkogamy, outcrossing and selfing rates with microsatellite loci, and assessed between generation (adults and seedlings) inbreeding, and inbreeding depression. Second, we compared the relationships between parameters in each population. Results point strong differences between populations: plants in Mapimí have, on average, approach herkogamy, higher outcrossing rate (t m = 0.68), lower primary selfing rate (r = 0.35), and lower inbreeding at equilibrium (F e = 0.24) and higher inbreeding depression (δ = 0.25), than the populations of Cañada. Outcrossing seems to be favored in Mapimí while selfing in Cañada. The relationship between r and F e were negatively associated with herkogamy in Mapimí; here, progenies derived from plants with no herkogamy or reverse herkogamy had higher selfing rate and inbreeding coefficient than plants with approach herkogamy. The difference F e-F is positively related to primary selfing rate (r) only in Cañada Moreno which suggests inbreeding depression in selfing individuals and then genetic purging. In conclusion, mating system evolution may occur differentially among maternal lineages within populations of Datura inoxia, in which approach herkogamy favors higher outcrossing rates and low levels of inbreeding and inbreeding depression, while no herkogamy or reverse herkogamy lead to the evolution of the "selfing syndrome" following the purge of deleterious alleles despite high inbreeding among individuals.
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Project description:Cancer is believed to be a result of accumulated mutations. However, this concept has not been fully confirmed owing to the impossibility of tracking down the ancestral somatic cell. We sought to verify the concept by exploring the correlation between cancer risk and mutation accumulation among different tissues. We hypothesized that the detected mutations through bulk tumor sequencing are commonly shared in majority, if not all, of tumor cells and are therefore largely a reflection of the mutations accumulated in the ancestral cell that gives rise to tumor. We collected a comprehensive list of mutation frequencies revealed by bulk tumor sequencing, and investigated its correlation with cancer risk to mirror the correlation between mutation accumulation and cancer risk. This revealed an approximate 1:1 relationship between mutation frequency and cancer risk in 41 different cancer types based on the sequencing data of 5,542 patients. The correlation strongly suggests that variation in cancer risk among tissues is mainly attributable to distinct mutation accumulation rates. Moreover, the correlation establishes a baseline to evaluate the effect of non-mutagenic carcinogens on cancer risk. Finally, our mathematic modeling provides a reasonable explanation to reinforce that cancer risk is predominantly determined by the first rate-limiting mutation.
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Project description:Biochar-different rates Raw sequence reads
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Project description:Evolution at high mutation rates is minimally affected by six processes: mutation-selection balance, error catastrophes, Muller's Ratchet, robustness and compensatory evolution, and clonal interference. Including all of these processes in a tractable, analytical model is difficult, but they can be captured in simulations that utilize realistic genotype-phenotype-fitness maps, as done here by modeling RNA folding. Subjecting finite, asexual populations to a range of mutation rates revealed simple criteria that predict when particular evolutionary processes are important. Populations were initiated with a genotype encoding the most fit phenotype. When purifying selection was strong relative to mutation, the initial genotype was replaced by one more mutationally robust, and the maximally fit phenotype was maintained in a mutation-selection balance where the deleterious mutation rate determined mean fitness. With weaker purifying selection, the most fit genotypes were lost. Although loss of the best genotype was ongoing and might have led to a progressive fitness decline, continual compensatory evolution led to an approximate fitness equilibration. Per total genomic mutation rate, mean fitness was similar for strong and weak purifying selection. These results represent a first step at separating interactions between evolutionary processes at high mutation rate, but additional theory is needed to interpret some outcomes.
| S-EPMC3389706 | biostudies-literature
Project description:In fragmented populations, genetic drift and selection reduce genetic diversity, which in turn results in a loss of fitness or in a loss of evolvability. Genetic rescue, that is, controlled input of diversity from distant populations, may restore evolutionary potential, whereas outbreeding depression might counteract the positive effect of this strategy. We carried out self-pollination and crosses within and between populations in an experimental subdivided population of a selfing species, Triticum aestivum L., to estimate the magnitude of these two phenomena. Surprisingly, for a self-fertilizing species, we found significant inbreeding depression within each population for four of the six traits studied, indicating that mildly deleterious mutations were still segregating in these populations. The progeny of within- and between-population crosses was very similar, indicating low between-population heterosis and little outbreeding depression. We conclude that relatively large population effective sizes prevented fixation of a high genetic load and that local adaptation was limited in these recently diverged populations. The kinship coefficient estimated between the parents using 20 neutral markers was a poor predictor of the progeny phenotypic values, indicating that there was a weak link between neutral diversity and genes controlling fitness-related traits. These results show that when assessing the viability of natural populations and the need for genetic rescue, the use of neutral markers should be complemented with information about the presence of local adaptation in the subdivided population.
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Project description:Great Ape Trio de novo Mutation Rate estimation
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