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B Charlesworth

Publications and source records attributed to B Charlesworth.

At least 73 records · Page 4Linked to original sources
PubMed1996

Recombination load associated with selection for increased recombination.

Experiments on Drosophila suggest that genetic recombination may result in lowered fitness of progeny (a 'recombination load'). This has been interpreted as evidence either for a direct effect of recombination on fitness, or for the maintenance of linkage disequilibria by epistatic selection. Here we show that such a recombination load is to be expected even if selection favours increased genetic recombination. This is because of the fact that, although a modifier may suffer an immediate loss of fitness if it increases recombination, it eventually becomes associated with a higher additive genetic variance in fitness, which allows a faster response to direction selection. This argument applies to mutation-selection balance with synergistic epistasis, directional selection on quantitative traits, and ectopic exchange among transposable elements. Further experiments are needed to determine whether the selection against recombination due to the immediate load is outweighed by the increased additive variance in fitness produced by recombination.

Animals↗
PubMed1996

The effect of recombination on background selection.

An approximate equation is derived, which predicts the effect on variability at a neutral locus of background selection due to a set of partly linked deleterious mutations. Random mating, multiplicative fitnesses, and sufficiently large population size that the selected loci are in mutation/selection equilibrium are assumed. Given these assumptions, the equation is valid for an arbitrary genetic map, and for an arbitrary distribution of selection coefficients across loci. Monte Carlo computer simulations show that the formula performs well for small population sizes under a wide range of conditions, and even seems to apply when there are epistatic fitness interactions among the selected loci. Failure occurred only with very weak selection and tight linkage. The formula is shown to imply that weakly selected mutations are more likely than strongly selected mutations to produce regional patterning of variability along a chromosome in response to local variation in recombination rates. Loci at the extreme tip of a chromosome experience a smaller effect of background selection than loci closer to the centre. It is shown that background selection can produce a considerable overall reduction in variation in organisms with small numbers of chromosomes and short maps, such as Drosophila. Large overall effects are less likely in species with higher levels of genetic recombination, such as mammals, although local reductions in regions of reduced recombination might be detectable.

Animals↗
PubMed1996

Background selection and patterns of genetic diversity in Drosophila melanogaster.

Theoretical models of the effects of selection against deleterious mutations on variation at linked neutral sites (background selection) are used to predict the relations between chromosomal location and genetic variability at the DNA level, in Drosophila melanogaster. The sensitivity of the predictions to variation in the mutation, selection and recombination parameters on which they are based is examined. It is shown that many features of the observed relations between chromosomal location and level of genetic diversity in D. melanogaster can be explained by background selection, especially if the weak selective forces acting on transposable elements are taken into account. In particular, the gradient in diversity in the distal portion of the X chromosome, and the lack of diversity on chromosome 4 and at the bases of the major chromosomes, can be fully accounted for. There are, however, discrepancies between predicted and observed values for some loci in D. melanogaster, which may reflect the effects of forces other than background selection.

Animals↗
PubMed1995

Speciation. Down the bottleneck?

Experiments in which laboratory populations of fruitflies have been repeatedly passed through bottlenecks fail to support 'founder-effect' models of speciation.

Animals↗
PubMed1995

The pattern of neutral molecular variation under the background selection model.

Stochastic simulations of the infinite sites model were used to study the behavior of genetic diversity at a neutral locus in a genomic region without recombination, but subject to selection against deleterious alleles maintained by recurrent mutation (background selection). In large populations, the effect of background selection on the number of segregating sites approaches the effect on nucleotide site diversity, i.e., the reduction in genetic variability caused by background selection resembles that caused by a simple reduction in effective population size. We examined, by coalescence-based methods, the power of several tests for the departure from neutral expectation of the frequency spectra of alleles in samples from randomly mating populations (Tajima's, Fu and Li's, and Watterson's tests). All of the tests have low power unless the selection against mutant alleles is extremely weak. In Drosophila, significant Tajima's tests are usually not obtained with empirical data sets from loci in genomic regions with restricted recombination frequencies and that exhibit low genetic diversity. This is consistent with the operation of background selection as opposed to selective sweeps. It remains to be decided whether background selection is sufficient to explain the observed extent of reduction in diversity in regions of restricted recombination.

Animals↗
PubMed1994

Evolution. How does increased fitness evolve?

Populations of bacteria exposed to a new environment have undergone adaptive evolutionary change over 10,000 generations. These populations provide a testing ground for alternative models of long-term evolution.

Adaptation, Biological↗
PubMed1994

The evolution of lethals in the t-haplotype system of the mouse.

The evolution of lethal haplotypes in the t-haplotype segregation distortion system of Mus is examined by mathematical and computer models. The models assume that there is reproductive compensation for the loss of lethal embryos, such that the net reproductive success of a females is not reduced in proportion to the frequency of lethal offspring which she produces. The initial population consists of a mixture of wild-type and homozygous male-sterile t-haplotypes. The failure of sterile males to reproduce may cause a higher fitness cost to mothers heterozygous for t-haplotypes than does elimination of a recessive lethal. Under certain conditions, a recessive lethal will spread and come to a polymorphic equilibrium. Wild-type, lethal and non-lethal haplotypes are all present at this equilibrium. If a second lethal mutation arises on a non-lethal t-haplotype in such an equilibrium population, it will increase in frequency and eventually displace the non-lethal t-haplotypes. A third lethal t-haplotype introduced at a low frequency into an equilibrium with two lethals can sometimes be selected for, although this is less likely if compensation is strong. The theoretical predictions are compared with data on natural populations.

Animals↗
PubMed1994

The evolutionary dynamics of repetitive DNA in eukaryotes.

Repetitive DNA sequences form a large portion of the genomes of eukaryotes. The 'selfish DNA' hypothesis proposes that they are maintained by their ability to replicate within the genome. The behaviour of repetitive sequences can result in mutations that cause genetic diseases, and confer significant fitness losses on the organism. Features of the organization of repetitive sequences in eukaryotic genomes, and their distribution in natural populations, reflect the evolutionary forces acting on selfish DNA.

Animals↗
PubMed1994

Genetic recombination. Patterns in the genome.

Recent analyses suggest that the GC content of gene sequences is related to the local frequency of genetic recombination; this may reflect the greater efficacy of natural selection when recombination is frequent.

Animals↗
PubMed1994

A genetic analysis of senescence in Drosophila.

Two attractive theories for the evolution of senescence are based on the principle that the force of natural selection decreases with age. The theories differ in the type of age-specific gene action that they assume. Antagonistic pleiotropy postulates that pleiotropic genes with positive effects early in life and negative effects of comparable magnitude late in life are favoured by selection, whereas genes with the reverse pattern of action are selected against. Mutation accumulation assumes that deleterious mutant alleles with age-specific effects will equilibrate at a lower frequency if their effects are expressed early rather than late in life. Explicit models demonstrate that both mechanisms can lead to the evolution of senescent life histories under reasonable conditions. Antagonistic pleiotropy has gained considerable empirical support, but the evidence in support of mutation accumulation is more sparse. Here we report that the genetic variability of mortality in male Drosophila melanogaster increases greatly at very late ages, as predicted by the mutation accumulation hypothesis. The rate of increase in mortality with age exhibits substantial genetic and environmental variability. This result provides a possible explanation for recent observations of non-increasing mortality rates in very old flies.

Aging↗
PubMed1994

The effect of background selection against deleterious mutations on weakly selected, linked variants.

This paper analyses the effects of selection against deleterious alleles maintained by mutation ('background selection') on rates of evolution and levels of genetic diversity at weakly selected, completely linked, loci. General formulae are derived for the expected rates of gene substitution and genetic diversity, relative to the neutral case, as a function of selection and dominance coefficients at the loci in question, and of the frequency of gametes that are free of deleterious mutations with respect to the loci responsible for background selection. As in the neutral case, most effects of background selection can be predicted by considering the effective size of the population to be multiplied by the frequency of mutation-free gametes. Levels of genetic diversity can be sharply reduced by background selection, with the result that values for sites under selection approach those for neutral variants subject to the same regime of background selection. Rates of fixation of slightly deleterious mutations are increased by background selection, and rates of fixation of advantageous mutations are reduced. The properties of sex-linked and autosomal loci in random-mating populations are compared, and the effects of background selection on asexual and self-fertilizing populations are considered. The implications of these results for the interpretation of studies of molecular evolution and variation are discussed.

Animals↗
PubMed1994

The distribution of transposable elements within and between chromosomes in a population of Drosophila melanogaster. III. Element abundances in heterochromatin.

The total genomic copy numbers of ten families of transposable elements of Drosophila melanogaster in a set of ten isogenic lines derived from a natural population were estimated by slot-blotting. The numbers of euchromatic copies of members of each family were determined for each line by in situ hybridization of element probes to polytene chromosomes. Heterochromatic numbers were estimated by subtraction of the euchromatic counts from the total numbers. There was considerable variation between element families and lines in heterochromatic abundances, and the variance between lines for many elements was much greater for the heterochromatin than for the euchromatin. The data are consistent with the view that much of the beta-heterochromatin consists of sequences derived from transposable elements. They are also consistent with the hypothesis that similar evolutionary forces control element abundances in both the euchromatin and heterochromatin, although amplification of inert sequences derived from transposable elements may be in part responsible for their accumulation in heterochromatin.

Animals↗
PubMed1994

Transposable element numbers in cosmopolitan inversions from a natural population of Drosophila melanogaster.

Population studies of the distribution of transposable elements (TEs) on the chromosomes of Drosophila melanogaster have suggested that their copy number increase due to transposition is balanced by some form of natural selection. Theory suggests that, as a consequence of deleterious ectopic meiotic exchange between TEs, selection can favor genomes with lower TE copy numbers. This predicts that TEs should be less deleterious, and hence more abundant, in chromosomal regions in which recombination is reduced. To test this, we surveyed the abundance and locations of 10 families of TEs in recombination-suppressing chromosomal inversions from a natural population. The sample of 49 chromosomes included multiple independent isolates of seven different inversions and a corresponding set of standard chromosomes. For all 10 TE families pooled, copy numbers were significantly higher overall within low frequency inversions than within corresponding regions of standard chromosomes. TEs occupied chromosomal sites at significantly higher frequencies within the In(3R)Mo and In(3R)K inversions than within the corresponding regions of standard 3R chromosomes. These results are consistent with the predictions of the ectopic exchange model.

Animals↗
PubMed1994

The effects of spontaneous mutation on quantitative traits. I. Variances and covariances of life history traits.

We have accumulated spontaneous mutations in the absence of natural selection in Drosophila melanogaster by backcrossing 200 heterozygous replicates of a single high fitness second chromosome to a balancer stock for 44 generations. At generations 33 and 44 of accumulation, we extracted samples of chromosomes and assayed their homozygous performance for female fecundity early and late in adult life, male and female longevity, male mating ability early and late in adult life, productivity (a measure of fecundity times viability) and body weight. The variance among lines increased significantly for all traits except male mating ability and weight. The rate of increase in variance was similar to that found in previous studies of egg-to-adult viability, when calculated relative to trait means. The mutational correlations among traits were all strongly positive. Many correlations were significantly different from 0, while none was significantly different from 1. These data suggest that the mutation-accumulation hypothesis is not a sufficient explanation for the evolution of senescence in D. melanogaster. Mutation-selection balance does seem adequate to explain a substantial proportion of the additive genetic variance for fecundity and longevity.

Animals↗
PubMed1993

Natural selection on multivariate traits in age-structured populations.

The theory of selection on multivariate traits in age-structured populations has important implications for empirical and theoretical studies of life-history evolution. A model of natural selection on a set of correlated quantitative traits with age structure is derived here, using an extension of previous work on selection at a single locus. This formulation provides an equation for the change of the mean of a vector of traits that is accurate is selection is weak, and does not require the population always to be in demographic equilibrium as selection proceeds. The treatment is extended to density-dependent populations, and to equilibrium populations under frequency-dependent selection. In addition, further approximations are derived that produce evolutionary equilibria equivalent to those predicted by optimization and evolutionarily stable strategy (ESS) theory. It is shown that the conditions for equilibrium are valid even if selection is strong.

Aging↗