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B Charlesworth

Publications and source records attributed to B Charlesworth.

At least 19 recordsLinked to original sources
PubMed2005

Steps in the evolution of heteromorphic sex chromosomes.

We review some recently published results on sex chromosomes in a diversity of species. We focus on several fish and some plants whose sex chromosomes appear to be 'young', as only parts of the chromosome are nonrecombining, while the rest is pseudoautosomal. However, the age of these systems is not yet very clear. Even without knowing what proportions of their genes are genetically degenerate, these cases are of great interest, as they may offer opportunities to study in detail how sex chromosomes evolve. In particular, we review evidence that recombination suppression occurs progressively in evolutionarily independent cases, suggesting that selection drives loss of recombination over increasingly large regions. We discuss how selection during the period when a chromosome is adapting to its role as a Y chromosome might drive such a process.

Animals↗
PubMed2004

Recombination and base composition: the case of the highly self-fertilizing plant Arabidopsis thaliana.

BACKGROUND: Rates of recombination can vary among genomic regions in eukaryotes, and this is believed to have major effects on their genome organization in terms of base composition, DNA repeat density, intron size, evolutionary rates and gene order. In highly self-fertilizing species such as Arabidopsis thaliana, however, heterozygosity is expected to be strongly reduced and recombination will be much less effective, so that its influence on genome organization should be greatly reduced. RESULTS: Here we investigated theoretically the joint effects of recombination and self-fertilization on base composition, and tested the predictions with genomic data from the complete A. thaliana genome. We show that, in this species, both codon-usage bias and GC content do not correlate with the local rates of crossing over, in agreement with our theoretical results. CONCLUSIONS: We conclude that levels of inbreeding modulate the effect of recombination on base composition, and possibly other genomic features (for example, transposable element dynamics). We argue that inbreeding should be considered when interpreting patterns of molecular evolution.

Arabidopsis↗
PubMed2004

Benefits of treating highly disabled migraine patients with zolmitriptan while pain is mild.

Clinical trials of migraine therapy often require treatment when migraine pain intensity is moderate or severe, but many physicians find this practice artificial and patients often prefer to treat while pain is mild. This randomized, placebo-controlled study assessed the efficacy of zolmitriptan 2.5 mg in treating migraine while pain is mild, in patients who typically experience migraine attacks that are initially mild, but progress to moderate or severe. The intent-to-treat population comprised 280 patients (138 zolmitriptan; 148 placebo), with mean MIDAS grades of 29.6 (zolmitriptan) and 27.6 (placebo). Zolmitriptan 2.5 mg provided a significantly higher pain-free rate at 2 h (43.4% vs. 18.4% placebo; P < 0.0001). Significantly fewer zolmitriptan patients reported progression of headache pain to moderate or severe intensity 2 h postdose (53.7% vs. 70.4% placebo; P < 0.01), or required further medication within 24 h (46.4% vs. 71.1% placebo; P < 0.0001). The efficacy of zolmitriptan was more pronounced in patients treating during the first 15 min following pain onset. Adverse events were reported in 31.2% of patients treated with zolmitriptan (vs. 11.3% for placebo), and the incidence was lower in patients who treated early after attack onset. Zolmitriptan provides high efficacy when treating migraine while pain is mild, with the clinical benefits being more pronounced when treating early after migraine onset.

Activities of Daily Living↗
PubMed2001

Patterns of age-specific means and genetic variances of mortality rates predicted by the mutation-accumulation theory of ageing.

A general quantitative genetic model of mutations with age-specific deleterious effects is developed. It is shown that, for the simplest case of a species with age-independent reproductive rates and extrinsic adult mortality rates, and no pleiotropic effects of age-specific mutations, exponential increases with age of both the mean and additive genetic variance of age-specific mortality rates are expected. Models where age-specific mutations have pleiotropic effects on mortality that extend either throughout adult life, or are confined to juvenile stages, produce equilibria with exponential increases in the mean and additive variance of mortality rates during much of adult life. However, the rates of increase diminish late in life, and can even become zero. Predictions concerning the additive genetic correlations in mortality rates between different ages are also developed. The predictions of the models are compared with data on humans and Drosophila.

Aging↗
PubMed2001

Genome sequences and evolutionary biology, a two-way interaction.

Complete genome sequences are accumulating rapidly, culminating with the announcement of the human genome sequence in February 2001. In addition to cataloguing the diversity of genes and other sequences, genome sequences will provide the first detailed and complete data on gene families and genome organization, including data on evolutionary changes. Reciprocally, evolutionary biology will make important contributions to the efforts to understand functions of genes and other sequences in genomes. Large-scale, detailed and unbiased comparisons between species will illuminate the evolution of genes and genomes, and population genetics methods will enable detection of functionally important genes or sequences, including sequences that have been involved in adaptive changes.

Journal Article↗
PubMed2001

Towards a complete sequence of the human Y chromosome.

A few dozen genes are known on the human Y chromosome. The completion of the human genome sequence will allow identification of the remaining loci, which should shed further light on the function and evolution of this peculiar chromosome.

Animals↗
PubMed2001

Genome analysis: More Drosophila Y chromosome genes.

The Drosophila melanogaster Y chromosome has long been known to contain few functional genes other than several required for male fertility. The D. melanogaster genome sequence has now allowed characterization of two more male fertility genes, shedding light on the function and evolution of Y chromosomes.

Animals↗
PubMed2001

The effect of life-history and mode of inheritance on neutral genetic variability.

Formulae for the effective population sizes of autosomal, X-linked, Y-linked and maternally transmitted loci in age-structured populations are developed. The approximations used here predict both asymptotic rates of increase in probabilities of identity, and equilibrium levels of neutral nucleotide site diversity under the infinite-sites model. The applications of the results to the interpretation of data on DNA sequence variation in Drosophila, plant, and human populations are discussed. It is concluded that sex differences in demographic parameters such as adult mortality rates generally have small effects on the relative effective population sizes of loci with different modes of inheritance, whereas differences between the sexes in variance in reproductive success can have major effects, either increasing or reducing the effective population size for X-linked loci relative to autosomal or Y-linked loci. These effects need to be accounted for when trying to understand data on patterns of sequence variation for genes with different transmission modes.

Animals↗
PubMed2001

Rates of movement and distribution of transposable elements in Drosophila melanogaster: in situ hybridization vs Southern blotting data.

Genomic copy numbers and the rates of movement of nine families of transposable elements (TEs) of Drosophila melanogaster were estimated in two sets of mutation accumulation lines: Beltsville and Madrid. Southern blotting was used to screen a large number of samples from both genetic backgrounds for TEs. The Madrid lines were also screened by in situ hybridization of TEs to polytene chromosomes, in order to obtain more detailed information about the behaviour of TEs in the euchromatin. Southern blotting data provided evidence of insertions and excision events in both genetic backgrounds, occurring at rates of approximately 10(-5) and 10(-6) per element copy per generation, respectively. In contrast, in situ data from the Madrid background presented a completely different picture, with no evidence for excisions, and a significantly higher rate of transposition (1.01 x 10(-4)). Direct comparison of the two data sets suggests that the Southern blotting technique had serious deficiencies: (i) it underestimated element abundance; (ii) it revealed less than 30% of the new insertions detected by in situ hybridization; and (iii) changes in the size of restriction fragments from any source were spuriously identified as simultaneous insertion-excision events. Our in situ data are consistent with previous studies, and suggest that selection is the main force controlling element spread by transposition.

Animals↗
PubMed2001

The speed of Muller's ratchet with background selection, and the degeneration of Y chromosomes.

The rate of accumulation of deleterious mutations by Muller's ratchet is investigated in large asexual haploid populations, for a range of parameters with potential biological relevance. The rate of this process is studied by considering a very simple model in which mutations can have two types of effect: either strongly deleterious or mildly deleterious. It is shown that the rate of accumulation of mildly deleterious mutations can be greatly increased by the presence of strongly deleterious mutations, and that this can be predicted from the associated reduction in effective population size (the background selection effect). We also examine the rate of the ratchet when there are two classes of mutation of similar but unequal effects on fitness. The accuracy of analytical approximations for the rate of this process is analysed. Its possible role in causing the degeneration of Y and neo-Y chromosomes is discussed in the light of our present knowledge of deleterious mutation rates and selection coefficients.

Animals↗
PubMed2001

A model of the evolution of the unusual sex chromosome system of Microtus oregoni.

In the creeping vole, Microtus oregoni, females are X0 and males are XY. In the female germ line, mitotic nondisjunction ensures that the products of meiosis all carry the X chromosome. Similarly, mitotic nondisjunction in the male germ line leads to the production of 0 and Y sperm. We propose that the present situation in M. oregoni has evolved by invasion of a normal XX/XY system by a mutant X chromosome, X', with a complete transmission advantage in X'X females, and a complete transmission disadvantage in X'Y males. X' is at best initially nearly neutral, but can gain a transmission advantage if it reaches a high enough frequency. This is due to the production of X0 females in matings between XX females and X'Y males; low fertility and embryo loss of such females reduce the fitness of the X chromosome in females, relative to that of X'. Under some conditions, however, the enhanced reproductive value of males, caused by the production of inviable Y0 embryos in X0 x X'Y matings, can outweigh any advantage to X'. Inbreeding also reduces any advantage to X'.

Animals↗
PubMed2001

Evidence for selection at the fused1 locus of Drosophila americana.

We analyze genetic variation at fused1, a locus that is close to the centromere of the X chromosome-autosome (X/4) fusion in Drosophila americana. In contrast to other X-linked and autosomal genes, for which a lack of population subdivision in D. americana has been observed at the DNA level, we find strong haplotype structure associated with the alternative chromosomal arrangements. There are several derived fixed differences at fused1 (including one amino acid replacement) between two haplotype classes of this locus. From these results, we obtain an estimate of an age of approximately 0.61 million years for the origin of the two haplotypes of the fused1 gene. Haplotypes associated with the X/4 fusion have less DNA sequence variation at fused1 than haplotypes associated with the ancestral chromosome arrangement. The X/4 haplotypes also exhibit clinal variation for the allele frequencies of the three most common amino acid replacement polymorphisms, but not for adjacent silent polymorphisms. These patterns of variation are best explained as a result of selection acting on amino acid substitutions, with geographic variation in selection pressures.

Animals↗
PubMed2000

Effects of metapopulation processes on measures of genetic diversity.

Many species persist as a metapopulation under a balance between the local extinction of subpopulations or demes and their recolonization through dispersal from occupied patches. Here we review the growing body of literature dealing with the genetic consequences of such population turnover. We focus our attention principally on theoretical studies of a classical metapopulation with a 'finite-island' model of population structure, rather than on 'continent-island' models or 'source-sink' models. In particular, we concern ourselves with the subset of geographically subdivided population models in which it is assumed that all demes are liable to extinction from time to time and that all demes receive immigrants. Early studies of the genetic effects of population turnover focused on population differentiation, such as measured by F(ST). A key advantage of F(ST) over absolute measures of diversity is its relative independence of the mutation process, so that different genes in the same species may be compared. Another advantage is that F(ST) will usually equilibrate more quickly following perturbations than will absolute levels of diversity. However, because F(ST) is a ratio of between-population differentiation to total diversity, the genetic effects of metapopulation processes may be difficult to interpret in terms of F(ST) on its own, so that the analysis of absolute measures of diversity in addition is likely to be informative. While population turnover may either increase or decrease F(ST), depending on the mode of colonization, recurrent extinction and recolonization is expected always to reduce levels of both within-population and species-wide diversity (piS and piT, respectively). One corollary of this is that piS cannot be used as an unbiased estimate of the scaled mutation rate, theta, as it can, with some assumptions about the migration process, in species whose demes do not fluctuate in size. The reduction of piT in response to population turnover reflects shortened mean coalescent times, although the distribution of coalescence times under extinction colonization equilibrium is not yet known. Finally, we review current understanding of the effect of metapopulation dynamics on the effective population size.

Genetic Techniques↗
PubMed2000

The degeneration of Y chromosomes.

Y chromosomes are genetically degenerate, having lost most of the active genes that were present in their ancestors. The causes of this degeneration have attracted much attention from evolutionary theorists. Four major theories are reviewed here: Muller's ratchet, background selection, the Hill Robertson effect with weak selection, and the 'hitchhiking' of deleterious alleles by favourable mutations. All of these involve a reduction in effective population size as a result of selective events occurring in a non-recombining genome, and the consequent weakening of the efficacy of selection. We review the consequences of these processes for patterns of molecular evolution and variation at loci on Y chromosomes, and discuss the results of empirical studies of these patterns for some evolving Y-chromosome and neo-Y-chromosome systems. These results suggest that the effective population sizes of evolving Y or neo-Y chromosomes are severely reduced, as expected if some or all of the hypothesized processes leading to degeneration are operative. It is, however, currently unclear which of the various processes is most important; some directions for future work to help to resolve this question are discussed.

Animals↗
PubMed2000

Reduced levels of microsatellite variability on the neo-Y chromosome of Drosophila miranda.

BACKGROUND: In many species, sex is determined by a system involving X and Y chromosomes, the latter having lost much of their genetic activity. Sex chromosomes have evolved independently many times, and several different mechanisms responsible for the degeneration of the Y chromosome have been proposed. Here, we have taken advantage of the secondary sex chromosome pair in Drosophila miranda to test for the effects of evolutionary forces involved in the early stages of Y-chromosome degeneration. Because of a fusion of one of the autosomes to the Y chromosome, a neo-Y chromosome and a neo-X chromosome have been formed, resulting in the transmission of formerly autosomal genes in association with the sex chromosomes. RESULTS: We found a 25-fold lower level of variation at microsatellites located on the neo-Y chromosome compared with homologous loci on the neo-X chromosome, or with autosomal and X-linked microsatellites. Sequence analyses of the region flanking the microsatellites suggested that the neo-sex chromosomes originated about 1 million years ago. CONCLUSIONS: Variability of the neo-Y chromosome of D. miranda is substantially reduced below expectations at mutation-drift equilibrium. Such a reduction is predicted by theories of the degeneration of the Y chromosome. Another possibility is that there is little or no mutation at microsatellite loci on a non-recombining chromosome such as the neo-Y, but this seems inconsistent with other data.

Animals↗
PubMed2000

Natural selection at work.

Although much is known about the genetic basis of reproductive isolation between species, little is understood about its underlying evolutionary causes. A study of two very closely related, but reproductively isolated, plant species has provided some valuable insights.

Plant Physiological Phenomena↗