Search PubMedSearch

Biomedical subjects

B Charlesworth

Publications and source records attributed to B Charlesworth.

At least 19 recordsLinked to original sources

The genomic mutation rate for fitness in Drosophila.

The mutation rate per genome for local affecting fitness is crucial in theories of the evolution of sex and recombination and of outbreeding mechanisms. Mutational variation in fitness may also be important in the evolution of mate choice in animals. No information is available on the rate at which spontaneous mutations with small effects on fitness arise, although viability (probability of survival to adulthood) has been studied in Drosophila melanogaster. These experiments involved the accumulation of spontaneous mutations in the virtual absence of natural selection, in a set of independently maintained lines with a common origin. The rates of decline in mean and increase in variance among lines permit estimation of limits to the mean number of new mutations arising per generation (U) and the average homozygous effect of a new mutation of minor effect(s). For the second chromosome of D. melanogaster, the value of U is at least 0.17 (ref. 7), and (1-h)s is less than 0.02, where hs is the average decline in fitness of heterozygotes. As the second chromosome is about 40% of the genome, these data indicate a mutation rate per haploid genome of at least 0.42 for viability. Here we present similar data on the effects of homozygous spontaneous mutations on a measure of fitness in D. melanogaster.

Animals

Accumulation of P elements in minority inversions in natural populations of Drosophila melanogaster.

The accumulation of a transposable element inside chromosomal inversions is examined theoretically by a mathematical model, and empirically by counts of P elements associated with inversion polymorphisms in natural populations of Drosophila melanogaster. The model demonstrates that, if heterozygosity for an inversion effectively reduces element associated production of detrimental chromosome rearrangements, a differential accumulation of elements is expected, with increased copy number inside the minority inversion. Several-fold differential accumulations are possible with certain parameter values. We present data on P element counts for inversion polymorphisms on all five chromosome arms of 157 haploid genomes from two African populations. Our observations show significantly increased numbers of elements within the regions associated with the least common, or minority arrangements, in natural inversion polymorphisms.

Animals

The effect of linkage and population size on inbreeding depression due to mutational load.

Using a stochastic model of a finite population in which there is mutation to partially recessive detrimental alleles at many loci, we study the effects of population size and linkage between the loci on the population mean fitness and inbreeding depression values. Although linkage between the selected loci decreases the amount of inbreeding depression, neither population size nor recombination rate have strong effects on these quantities, unless extremely small values are assumed. We also investigate how partial linkage between the loci that determine fitness affects the invasion of populations by alleles at a modifier locus that controls the selfing rate. In most of the cases studied, the direction of selection on modifiers was consistent with that found in our previous deterministic calculations. However, there was some evidence that linkage between the modifier locus and the selected loci makes outcrossing less likely to evolve; more losses of alleles promoting outcrossing occurred in runs with linkage than in runs with free recombination. We also studied the fate of neutral alleles introduced into populations carrying detrimental mutations. The times to loss of neutral alleles introduced at low frequency were shorter than those predicted for alleles in the absence of selected loci, taking into account the reduction of the effective population size due to inbreeding. Previous studies have been confined to outbreeding populations, and to alleles at frequencies close to one-half, and have found an effect in the opposite direction. It therefore appears that associations between neutral and selected loci may produce effects that differ according to the initial frequencies of the neutral alleles.

Genetic Linkage

The distribution of transposable elements within and between chromosomes in a population of Drosophila melanogaster. I. Element frequencies and distribution.

Data were collected on the distribution of nine families of transposable elements among second and third chromosomes isolated from a natural population of Drosophila melanogaster, by means of in situ hybridization of element probes to polytene chromosomes. It was found that the copy numbers per chromosome in the distal sections of the chromosome arms followed a Poisson distribution. Elements appeared to be distributed randomly along the distal sections of the chromosome arms. There was no evidence for linkage disequilibrium in the distal sections of the chromosomes, but some significant disequilibrium was detected in proximal regions. There were many significant correlations between different element families with respect to the identity of the sites that were occupied in the sample. There were also significant correlations between families with respect to sites at which elements achieved relatively high frequencies. Element frequencies per chromosome band were generally low in the distal sections, but were higher proximally. These results are discussed in the light of models of the population dynamics of transposable elements. It is concluded that they provide strong evidence for the operation of a force or forces opposing transpositional increase in copy number. The data suggest that the rate of transposition per element per generation is of the order of 10(-4), for the elements included in this study.

Animals

The distribution of transposable elements within and between chromosomes in a population of Drosophila melanogaster. II. Inferences on the nature of selection against elements.

Data were collected on the distribution of nine families of transposable elements among a sample of autosomes isolated from a natural population of Drosophila melanogaster, by means of in situ hybridization of biotinylated probes to polytene chromosomes. There is no general tendency for elements to accumulate at the tips of chromosomes. Elements tend to be present in excess of random expectation in the euchromatin proximal to the centromeres of the major autosomes, and on chromosome four. There is considerable heterogeneity between different families in the extent of this excess. The overall abundance of element families is inversely related to the extent to which they accumulate proximally. The level of proximal accumulation for the major autosomes is similar to that on the fourth chromosome, but less than that for the X chromosome. There is an overall deficiency of elements in the mid-section of the X compared with the mid-sections of the major autosomes, with considerable heterogeneity between families. The magnitude of this deficiency is positively related to the extent to which elements accumulate proximally. No such deficiency is seen if the proximal regions of the X and autosomes are compared. There is a small and non-significant excess of elements in third chromosomes carrying inversions. There is some between-year heterogeneity in element abundance. The implications of these findings are discussed, and it is concluded that they generally support the hypothesis that transposable element abundance is regulated primarily by the deleterious fitness consequences of meiotic ectopic exchange between elements. If this is the case, such exchange must be very infrequent in the proximal euchromatin, and the elements detected in population surveys of this kind must be inserted into sites where they have negligible mutational effects on fitness.

Animals

The evolution of sex chromosomes.

Structurally distinct sex chromosomes (X and Y) are the most familiar mode of genetic sex determination and have evolved independently in many different taxa. The evolutionary paths by which their characteristic properties may have evolved are reviewed. These properties include the failure of X and Y to recombine through much or all of their length, the genetic inertness of much of the Y chromosome, dosage compensation of the activity of X chromosomal loci, and the accumulation of repeated DNA sequences on the Y chromosome.

Animals

Transposable elements in natural populations with a mixture of selected and neutral insertion sites.

This paper examines models of the population dynamics of transposable elements when chromosomal sites vary with respect to the effect on fitness of mutations caused by element insertions. Element abundance is assumed to be stabilised solely by the joint results of transposition, excision, and selection against insertional mutations. When there are only two classes of site, selected and neutral, it is hard to find parameter values for which numbers of elements are maintained that match the findings from surveys of Drosophila populations, as elements tend to accumulate at high frequencies at the neutral sites. It is similarly hard to produce realistic equilibria with three classes of site (strongly selected, weakly selected, and neutral), when elements can transpose out of the neutral sites. If transposition from neutral sites is impossible, as might be the case for elements inserted into centric heterochromatin, then realistic equilibria can be generated if there is very weak selection against elements inserted into the majority of non-neutral sites. This model predicts a modest over-representation of elements at the neutral sites. It also predicts that elements should be under-represented on the X chromosome compared with the autosomes, but this is not generally found to be the case. It is concluded that selection against insertional mutations is unlikely to be the major factor involved in the containment of element abundance.

Animals

Mutation-selection balance and the evolutionary advantage of sex and recombination.

Mutation-selection balance in a multi-locus system is investigated theoretically, using a modification of Bulmer's infinitesimal model of selection on a normally-distributed quantitative character, taking the number of mutations per individual (n) to represent the character value. The logarithm of the fitness of an individual with n mutations is assumed to be a quadratic, decreasing function of n. The equilibrium properties of infinitely large asexual populations, random-mating populations lacking genetic recombination, and random-mating populations with arbitrary recombination frequencies are investigated. With 'synergistic' epistasis on the scale of log fitness, such that log fitness declines more steeply as n increases, it is shown that equilibrium mean fitness is least for asexual populations. In sexual populations, mean fitness increases with the number of chromosomes and with the map length per chromosome. With 'diminishing returns' epistasis, such that log fitness declines less steeply as n increases, mean fitness behaves in the opposite way. Selection on asexual variants and genes affecting the rate of genetic recombination in random-mating populations was also studied. With synergistic epistasis, zero recombination always appears to be disfavoured, but free recombination is disfavoured when the mutation rate per genome is sufficiently small, leading to evolutionary stability of maps of intermediate length. With synergistic epistasis, an asexual mutant is unlikely to invade a sexual population if the mutation rate per diploid genome greatly exceeds unity. Recombination is selectively disadvantageous when there is diminishing returns epistasis. These results are compared with the results of previous theoretical studies of this problem, and with experimental data.

Animals

A study of ten families of transposable elements on X chromosomes from a population of Drosophila melanogaster.

Data were collected on the distribution of ten families of transposable elements among fourteen X chromosomes isolated from a natural population of Drosophila melanogaster, by means of in situ hybridization to polytene chromosomes. It was found that, with the exception of roo, the copy number per chromosome followed a Poisson distribution. There was no evidence for linkage disequilibrium, either within or between families. Some pairs of families of elements were correlated with respect to the identity of the sites that were occupied in the sample, although there was no evidence for a correlation with respect to the sites at which elements attained relatively high frequencies. Elements appeared to be distributed randomly along the distal part of the X chromosome. There was, however, a strong tendency for elements to accumulate at the base of the chromosome. Element frequencies per chromosome band were generally low, except at the base of the chromosome where bands in subdivisions 19E and 20A sometimes had high frequencies of occupation. These results are discussed in the light of models of the population dynamics of transposable elements. It is concluded that they provide strong evidence for the operation of a force or forces opposing transpositional increase in copy number. The accumulation of elements at the base of the chromosome is consistent with the idea that unequal exchange between elements at non-homologous sites is such a force, although other possibilities cannot be excluded at present. The data suggest that the rate of transposition per element per generation is of the order of 10(-4), for the elements included in this study.

Animals

Genetic analysis of X-linked sterility in hybrids between three sibling species of Drosophila.

Three morphological markers (yellow, miniature, and forked) are used to map the location of X-chromosome segments causing male sterility in Drosophila simulans/D. mauritiana and D. simulans/D. sechellia hybrids. In both hybridizations at least three sections of the chromosome contain genes with substantial effects on sterility. This represents the maximum genetic divergence detectable with the three markers, suggesting that the X chromosome contains many loci affecting postzygotic reproductive isolation. The tight linkage between some markers and "sterility loci" may be useful in localizing and later cloning genes important in speciation.

Animals

The evolution of mate choice in a fluctuating environment.

This paper analyzes the evolutionary dynamics of a locus controlling the degree of female mating preference in a temporally fluctuating environment. Preference for mating with males with respect to their genotypes at a locus that is subject to temporally varying natural selection pressure is considered first. With weak selection and free recombination between the choice locus and the selected locus, preference for mating with heterozygotes appears to be favored. With strong selection, preference for homozygous mates may be favored. In each case, choice alleles may increase from very low initial frequencies to near fixation, in contrast to previous models of mate choice in varying environments. Linkages between the two loci has complex effects on the strength and direction of selection for mate choice. Preference for mating with males with the currently fitter genotypes at the locus under natural selection is also modelled. Provided that the environmental period is not too short, a rare allele conferring such preference may be favored and spread to fixation. Strong natural selection, tight linkage and a short environmental period may produce polymorphism for the level of mate choice.

Alleles

The maintenance of transposable elements in natural populations.

Models of the maintenance of transposable elements in randomly mating host populations are reviewed. It is shown that the data on the distribution of copy numbers between individuals are largely concordant with what is expected on the basis of the Mendelian transmission of elements. The role of regulation of rates of transposition, and of various modes of natural selection, in maintaining an equilibrium in copy numbers in the face of transpositional increase in copy number is discussed. Tests for the role of selection against insertional mutations and against chromosome rearrangements induced by exchange between homologous elements located at nonhomologous chromosome locations are discussed. Reasons for expecting elements to accumulate in chromosome regions where crossing over is restricted are discussed, and data suggesting the existence of such an effect are described. Theory and data on the probability distribution of element frequencies at individual chromosomal sites are described. It is concluded that the available population data are consistent with the notion that element abundances are largely controlled by the interaction of transpositional increase in copy number with opposing forces.

Animals