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D Charlesworth

Publications and source records attributed to D Charlesworth.

At least 55 records · Page 3Linked to original sources
PubMed1998

Rates of spontaneous mutation.

Rates of spontaneous mutation per genome as measured in the laboratory are remarkably similar within broad groups of organisms but differ strikingly among groups. Mutation rates in RNA viruses, whose genomes contain ca. 10(4) bases, are roughly 1 per genome per replication for lytic viruses and roughly 0.1 per genome per replication for retroviruses and a retrotransposon. Mutation rates in microbes with DNA-based chromosomes are close to 1/300 per genome per replication; in this group, therefore, rates per base pair vary inversely and hugely as genome sizes vary from 6 x 10(3) to 4 x 10(7) bases or base pairs. Mutation rates in higher eukaryotes are roughly 0.1-100 per genome per sexual generation but are currently indistinguishable from 1/300 per cell division per effective genome (which excludes the fraction of the genome in which most mutations are neutral). It is now possible to specify some of the evolutionary forces that shape these diverse mutation rates.

Animals↗
PubMed1998

The male-sterility polymorphism of Silene vulgaris: analysis of genetic dat from two populations and comparison with Thymus vulgaris.

Results are given of genetic studies of male sterility using plants from two natural populations from Sussex, England. Both populations have substantial frequencies of females, approximately 0.25 in population 1 and 0.60 in population 3. As in the few other gynodioecious populations studied in detail, many genetic factors are present. In population 1, there are at least two, and more likely three, different cytoplasmic types, one of which appears to produce male sterility in progeny from any hermaphrodite pollen donor; in other words restorer alleles for this cytoplasm are rare or absent from the population. The other two populations can be carried in hermaphrodites that have the dominant restorers. In population 1, there are also probably three restorer loci with complementary recessive male-sterility alleles, as well as a locus with duplicate action, which cannot produce male sterility unless the plant is also homozygous for the recessive allele at another locus. The results from population 3 are quite similar, though there was no evidence in this population for an unrestored sterility cytoplasm. A similar joint nucleocytoplasmic model with multiple restorers fits data from Thymus vulgaris.

Genes, Plant↗
PubMed1998

The evolution of the alcohol dehydrogenase gene family by loss of introns in plants of the genus Leavenworthia (Brassicaceae).

We present results showing that several species in the plant genus Leavenworthia, in the Brassica family, have three alcohol dehydrogenase loci, unlike Arabidopsis thaliana, which has only a single classical (class P) alcohol dehydrogenase locus. Based on a portion of the sequence, the alcohol dehydrogenase loci of Leavenworthia show about 92%-93% amino acid sequence identity to that of the A. thaliana alcohol dehydrogenase. The great majority of the sequence differences from the A. thaliana Adh-coding sequence, and also between three different Leavenworthia species, are synonymous, suggesting that all are currently functional (or have been in the recent evolutionary past). The loci differ in the numbers of introns present, with one locus (Adh-3) having no introns present. RT-PCR tests detect expression of all three loci. Linkage data using variant alleles identified by single-strand conformation polymorphism analysis show that the three Leavenworthia loci are not closely linked. The results therefore suggest that the Adh-3 locus may have arisen via an mRNA intermediate but, despite loss of the introns, is expressed.

Alcohol Dehydrogenase↗
PubMed1998

Some evolutionary consequences of deleterious mutations.

Most mutations with observable phenotypic effects are deleterious. Studies of Drosophila and inbred plant populations suggest that a new individual may have a mean number of new deleterious mutations that exceeds one-half. Most of these have relatively small homozygous effects and reduce fitness by 1-2% when heterozygous. Several striking features of present-day organisms have apparently evolved in response to the constant input of deleterious alleles by recurrent mutation. For example, the adaptations of hermaphroditic organisms for outcrossing have been widely interpreted in terms of the benefits of avoiding the reduced fitness of inbred progeny, which is partly due to deleterious mutations. Population genetic models of modifiers of the breeding system in the presence of genome-wide deleterious mutation are reviewed and their predictions related to genetic and comparative data. The evolution of degenerate Y chromosomes is a phenomenon that may be caused by the accumulation of deleterious mutations. The population genetic mechanisms that can drive this degenerations are reviewed and their significance assessed in the light of available data.

Animals↗
PubMed1997

Seeing selection in S allele sequences.

New data on allelic sequence diversity in natural populations provide evidence for natural selection acting on the self-incompatibility loci of two plant species; there are interesting parallels with, and differences from, other polymorphic systems such as mammalian MHC loci.

Alleles↗
PubMed1997

Rapid fixation of deleterious alleles can be caused by Muller's ratchet.

Theoretical arguments are presented which suggest that each advance of Muller's ratchet in a haploid asexual population causes the fixation of a deleterious mutation at a single locus. A similar process operates in a diploid, fully asexual population under a wide range of parameter values, with respect to fixation within one of the two haploid genomes. Fixations of deleterious mutations in asexual species can thus be greatly accelerated in comparison with a freely recombining genome, if the ratchet is operating. In a diploid with segregation of a single chromosome, but no crossing over within the chromosome, the advance of the ratchet can be decoupled from fixation if mutations are sufficiently close to recessivity. A new analytical approximation for the rate of advance of the ratchet is proposed. Simulation results are presented that validate the assertions about fixation. The simulations show that none of the analytical approximations for the rate of advance of the ratchet are satisfactory when population size is large. The relevance of these results for evolutionary processes such as Y chromosome degeneration is discussed.

Alleles↗
PubMed1997

The effects of local selection, balanced polymorphism and background selection on equilibrium patterns of genetic diversity in subdivided populations.

Levels of neutral genetic diversity in populations subdivided into two demes were studied by multilocus stochastic simulations. The model includes deleterious mutations at loci throughout the genome, causing 'background selection', as well as a single locus at which a polymorphism is maintained, either by frequency-dependent selection or by local selective differences. These balanced polymorphisms induce long coalescence times at linked neutral loci, so that sequence diversity at these loci is enhanced at statistical equilibrium. We study how equilibrium neutral diversity levels are affected by the degree of population subdivision, the presence or absence of background selection, and the level of inbreeding of the population. The simulation results are compared with approximate analytical formulae, assuming the infinite sites neutral model. We discuss how balancing selection can be distinguished from local selection, by determining whether peaks of diversity in the region of the polymorphic locus are seen within or between demes. The width of such diversity peaks is shown to depend on the total species population size, rather than local deme sizes. We show that, with population subdivision, local selection enhances between-deme diversity even at neutral sites distant from the polymorphic locus, producing higher FST values than with no selection; very high values can be generated at sites close to a selected locus. Background selection also increases FST, mainly because of decreased diversity within populations, which implies that its effects may be distinguishable from those of local selection. Both effects are stronger in selfing than outcrossing populations. Linkage disequilibrium between neutral sites is generated by both balancing and local selection, especially in selfing populations, because of linkage disequilibrium between the neutral sites and the selectively maintained alleles. We discuss how these theoretical results can be related to data on genetic diversity within and between local populations of a species.

Alleles↗
PubMed1997

Point estimation and graphical inference of marginal dominance for two viability loci controlling inbreeding depression.

A deterministic analysis is conducted to examine marginal dominance for two linked viability loci influencing inbreeding depression and its graphical inferences. Four estimators of marginal dominance are derived, assuming a biallelic marker locus completely linked to one of the viability loci, and the biases in expected estimates due to the other deleterious locus are discussed. Three conditions under which apparent partial dominance or underdominance could occur are found, i.e. when two multiplicative, partially recessive loci are linked in coupling phase and when two synergistic, highly overdominant loci are linked in coupling or repulsion phases. Expected frequencies of the three marker genotypes in selfed progeny are derived, considering two linkage phases, two types of marker locus position with respect to the viability loci, and the multiplicative and synergistic fitness models. Segregation ratios are generated for the marker locus linked to either two overdominant or partially recessive loci and plotted in gene action graphs to examine the robustness of the graphical inferences of gene action due to the presence of an additional linked viability locus. Under a multiplicative fitness model, the presence of an additional partially recessive or overdominant locus in the vicinity of the marker locus does not greatly affect the graphical inferences of the relative role of partially recessive or overdominant genes in expression of inbreeding depression. A marker linked to two synergistic, highly overdominant loci can behave as though linked to a partially recessive, partially dominant or underdominant locus, even with relatively weak synergism.

Genes, Dominant↗
PubMed1997

Lack of degeneration of loci on the neo-Y chromosome of Drosophila americana americana.

The extent of genetic degeneration of the neo-Y chromosome of Drosophila americana americana has been investigated. Three loci, coding for the enzymes enolase, phosphoglycerate kinase and alcohol dehydrogenase, have been localized to chromosome 4 of D. a. americana, which forms the neo-Y and neo-X chromosomes. Crosses between D.a. americana and D. virilis or D. montana showed that the loci coding for these enzymes carry active alleles on the neo-Y chromosome in all wild-derived strains of americana that were tested. Intercrosses between a genetically marked stock of virilis and strains of americana were carried out, creating F3 males that were homozygous for sections of the neo-Y chromosome. The sex ratios in the F3 generation of the intercrosses showed that no lethal alleles have accumulated on any of the neo-Y chromosomes tested. There was evidence for more minor reductions in fitness, but this seems to be mainly caused by deleterious alleles that are specific to each strain. A similar picture was provided by examination of the segregation ratios of two marker genes among the F3 progeny. Overall, the data suggest that the neo-Y chromosome has undergone very little degeneration, certainly not to the extent of having lost the functions of vital genes. This is consistent with the recent origin of the neo-Y and neo-X chromosomes, and the slow rates at which the forces that cause Y chromosome degeneration are likely to work.

Animals↗
PubMed1996

Albumin-coated vascular prostheses: A five-year follow-up.

In June 1989, we set out to implant 200 albumin-coated aortic bifurcation grafts and to track the patients for a period of 5 years to determine whether coating the prosthesis with albumin affected the patency or the incidence of complication. Two hundred and one prostheses were implanted between June 1989 and July 1991. The primary and secondary patency at 5 years was 95% and 98%, respectively. No relation between gender and patency or between the state of the runoff and patency was found, but there was a statistically significant relation between age and patency (p = 0.00). Graft infection was recorded in three patients (1.5%). There were no instances of bleeding through the graft at the time of implantation. The mean intra- and postoperative blood requirement was 2 units. There have been no incidences of false aneurysm in the groin. We conclude that there are no disadvantages of coating the prosthesis with albumin, and a trial of coated versus uncoated prostheses would be impractical.

Adult↗
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↗
PubMed1995

Hybrid speciation. Evolution under the microscope.

Detailed genetic maps of three related sunflower species support the view that one species originated relatively recently from the other two by hybrid speciation, providing the first good evidence for this theory of speciation.

Biological Evolution↗
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

Plant self-incompatibility. The key to specificity.

Experiments with transgenic plants provide strong evidence that the locus controlling the female side of recognition in self-incompatibility has been correctly identified, and supoort the view that a ribonuclease is involved.

Alleles↗
PubMed1994

Comparison of measurement of stump pressure and transcranial measurement of flow velocity in the middle cerebral artery in carotid surgery.

Transcranial Doppler ultrasound measurement of the velocity of blood flow in the middle cerebral artery (MCA) was performed in 24 consecutive patients undergoing carotid endarterectomy. Measurements were performed preoperatively at rest, following common carotid artery compression, and continuously during surgery. In addition, internal carotid artery stump pressures were measured and a subjective assessment of back flow was made. No relationship between MCA flow velocity and stump pressure following carotid clamping was demonstrated. Peak and mean MCA flow velocity was significantly lower in patients with stump pressures < 30 mm Hg (p < 0.03) and those with poor back flow (p < 0.02).

Blood Flow Velocity↗
PubMed1994

Elective rather than emergency intervention for acute renal artery occlusion with anuria.

We describe a case in which surgical revascularisation was electively delayed until 27 days after acute renal artery occlusion, allowing surgery to be performed after a period of haemodialysis and pre-operative cardiac assessment. Owing to the collateral blood supply to the kidney, emergency surgery in cases of acute renal artery occlusion may not be necessary, and may be hazardous.

Acute Disease↗
PubMed1994

An evaluation of patients with severe intermittent claudication and the effect of treatment with naftidrofuryl.

A randomized placebo-controlled study was undertaken in 188 patients with severe intermittent claudication attending two vascular clinics in Manchester and Liverpool. After a 4-week run-in period, patients received active or placebo treatment for 24 weeks. Patients were assessed on a treadmill prior to the 4-week run-in period, at randomization, and at 8, 16, and 24 weeks. Outcome was measured in terms of change in pain-free walking distance, maximum walking distance, and pressure indices. In this severe claudication population, in which the patients presented with a mean pain-free walking distance of 60 m, an intention-to-treat analysis demonstrated that the outcome in the naftidrofuryl-treated group was significantly better than in the group receiving placebo (p = 0.045). Additionally, 7% of patients in the naftidrofuryl group deteriorated compared with 22% in the placebo group (p = 0.005). Of the various risk factors that were recorded during the study--smoking habits, the presence of hypertension, diabetes, obesity, and duration of illness--only duration of illness had a significant influence on outcome. Maximum walking distances alone were not significantly influenced by treatment, but the use of a combined index of pain-free walking distance, maximum walking distance, and pressure indices to record success or failure confirmed a significant treatment effect (p = 0.047). A higher incidence of minor gastrointestinal symptoms was recorded in the naftidrofuryl-treated group. Treatment with naftidrofuryl was shown to prevent or slow the deterioration observed in a group of patients with severe claudication over a 24-week period.

Adult↗