Biomedical subjects

L Partridge

Publications and source records attributed to L Partridge.

At least 37 records · Page 2Linked to original sources

PubMed2000

The identification of endothelial cell autoantigens.

The identity of many endothelial cell autoantigens remains unclear. This study has used human monoclonal anti-endothelial cell autoantibodies isolated from patients with SLE to identify endothelial autoantigens. Thirteen antibodies reactive with endothelial cell membrane preparations were isolated and cloned, one of which has previously been demonstrated to be pro-inflammatory. Western blotting demonstrates that these antibodies recognize a variety of proteins in endothelial cell membrane preparations. Further characterization of five antibodies by cDNA library screening, immunofluorescence and Western blotting proves that two of these antibodies recognized the cytoskeletal proteins tubulin and vimentin. A further antibody identified a clone derived from human collagenase, an identification supported by Western blotting. The multiple clones selected by other antibodies are not compatible with the molecular weight of the antigen recognized in Western blotting studies. This study has clearly identified two endothelial cell autoantigens present in membrane preparations and provides strong evidence as to the identity of a third.

Antibodies, Monoclonal↗

PubMed2000

Measuring fitness by means of balancer chromosomes.

We present the theoretical background to a new method for measuring genetic variation for total fitness in Drosophila. The method allows heterozygous effects on total fitness of whole wild-type chromosomes to be measured under normal demography with overlapping generations. The wild-type chromosomes are competed against two balancer chromosomes (B1, B2, say), providing a standard genotype B1/B2 against which variation in the fitness effects of the wild-type chromosomes can be assessed. Fitness can be assessed in two ways: (i) at equilibrium of all three chromosomes under heterozygote advantage, and (ii) during displacement of one balancer by the other. Equilibrium with all three chromosomes present will be achieved only if the wild-type homozygote is not too fit, and if the fitnesses of the three heterozygotes are not too unequal. These conditions were not satisfied for any of a sample of 12 lethal-bearing chromosomes isolated from a random-bred laboratory population of Drosophila. At equilibrium, genotypic frequencies show low sensitivity to changes in genotypic fitness. Furthermore, where all four genotypes are viable and fertile, supplementary information from cages with only two chromosomes present and from direct measurements of pre-adult viability are required to estimate fitnesses from frequencies. The invasion method has the advantages of a greater sensitivity and of not requiring further data to estimate fitnesses if the wild-type homozygote is fertile. However, it requires that multiple samples be taken as the invasion progresses. In a discrete generation model, generation time influences fitness estimates from this method and is difficult to estimate accurately from the data. A full age-structured model can also be applied to the data from both types of experiment. For the invasion method, this gives fitness estimates close to those from the discrete generation model.

Adaptation, Physiological↗

PubMed2000

Cellular basis of wing size variation in Drosophila melanogaster: a comparison of latitudinal clines on two continents.

We investigated the cellular basis of two extensive, continuous, latitudinal, genetic, body size clines of Drosophila melanogaster by measuring wing area and cell size in the wing blade of adult flies reared under standard, laboratory conditions. We report that the contribution of cell size to an Australian cline is much smaller than that to a South American cline. The data suggest that neither cell size nor cell number were the targets of selection, but rather wing area itself, or a trait closely related to it. We hypothesize that the differences between the continents were caused by differences in the initial pattern of genetic variation for the cell traits and/or by the direction of selection on the source populations of the clines. Despite large differences between continents in the cellular basis of the latitudinal variation, multiple regression analysis, using the individual variation within populations, showed that the relationship between cell size and cell number was changed with latitude in the same way in the two clines. The relative contribution of cell number to wing area variation increased with latitude, probably because of compensatory interactions with cell size as a consequence of the latitudinal increase in cell number. Our findings are discussed in relation to the cellular basis of evolutionary change in laboratory thermal selection lines and natural populations along latitudinal clines.

Analysis of Variance↗

PubMed2000

Why it is difficult to model sperm displacement in Drosophila melanogaster: the relation between sperm transfer and copulation duration.

We have investigated the effects of experimental manipulation of copulation duration on sperm displacement in Drosophila melanogaster. Both spermless and normal males were used as second (displacing) males in the experiments. Displacement induced in the absence of sperm, that is, by males that pass accessory gland fluid alone, was a relatively inefficient process and produced much lower levels of displacement than normal males. Therefore, the presence of second-male sperm is necessary (but unlikely sufficient) for the high levels of displacement commonly observed in D. melanogaster. Furthermore, when second matings were interrupted at various times after the initiation of copulation, the distribution of displacement was strongly bimodal. We conclude that sperm transfer is relatively rapid, beginning shortly after the initiation of copulation, and is essentially complete before the midpoint of copulation. Therefore, sperm transfer bears no simple relation to copulation duration. Because it would be difficult to manipulate the numbers of sperm transferred by manipulating copulation duration, methods used to study sperm displacement in other insect species are unlikely to be appropriate for D. melanogaster. We also investigated why males mate for more than twice the duration that appears to be necessary to complete sperm transfer. Experimental interruption of first matings indicated that the extra copulation time serves to delay female remating, rather than to increase that rate at which of offspring are sired before remating.

Animals↗

PubMed2000

Starvation resistance and adult body composition in a latitudinal cline of Drosophila melanogaster.

Latitudinal geographic variation in Drosophila melanogaster is pervasive. Parallel clines in traits such as body size, egg size, ovariole number, and development time have been found on several continents throughout the world. However, a cline in starvation resistance and fat content in D. melanogaster has so far been found only in India. Here we investigate starvation resistance and fat content in 10 populations from South America, in which clines in body size, egg size, and development time have previously been found. We find no evidence for a cline in starvation resistance or fat content in South America. We therefore suggest that the cline in starvation resistance in India may have evolved in response to specific climatic variation found only in India.

Animals↗

PubMed2000

Selection on age at reproduction in Drosophila melanogaster: female mating frequency as a correlated response.

We examined the effect of selection for age at reproduction on female mating frequency and fertility in female Drosophila melanogaster. Selection for increased age at reproduction (and hence increased lifespan) resulted in higher late life female mating frequencies, while females selected for younger ages at reproduction showed increased early life mating frequencies. These results indicate that the response to selection on age at reproduction has involved changes in the scheduling of female reproductive behavior.

Aging↗

PubMed1999

A delayed wave of death from reproduction in Drosophila.

Mortality rates typically increase rapidly at the onset of aging but can decelerate at later ages. Reproduction increases the death rate in many organisms. To test the idea that a delayed impact of earlier reproduction contributes to both an increase in death rates and a later deceleration in mortality, the timing of the surplus mortality produced by an increased level of egg production was measured in female Drosophila. Reproduction produced a delayed wave of mortality, coincident with the sharp increase in death rates at the onset of aging and the subsequent deceleration of mortality. These results suggest that aging has evolved primarily because of the damaging effects of reproduction earlier in life, rather than because of mutations that have detrimental effects only at late ages.

Aging↗

PubMed1999

Another set of responses and correlated responses to selection on age at reproduction in Drosophila melanogaster.

Ageing is the decline in survival probability and fertility later in adult life. It can evolve through mutation accumulation and pleiotropy. Artificial selection by age at reproduction is a useful method for detecting the effects of pleiotropy, and for producing lines that differ in their rate of ageing for further analysis. However, the approach has encountered difficulties from gene-environment interaction and inadvertent selection. We have produced a new set of selection lines in Drosophila melanogaster, breeding from either 'young' or 'old' adults, and avoiding some of the difficulties present in previous studies. Breeding from older adults resulted in an evolutionary increase in survival but, contrary to all previous studies using this method, in no increase in late-life fertility. The increase in survival was accompanied by an evolutionary decline in fertility early in adult life, confirming the importance of pleiotropy in the evolution of ageing. Contrary to previous studies, there were no correlated responses to selection in the pre-adult period; development time, larval competitive ability and adult size achieved did not differ between the lines from the two selection regimes.

Aging↗

PubMed1999

Mating-induced inhibition of remating in female Mediterranean fruit flies Ceratitis capitata.

Mechanisms producing inhibition of remating in mated female Mediterranean fruit flies Ceratitis capitata, were investigated by matings with surgically altered males. Comparison of remating by females mated with either intact control males or males with a shortened penis, showed that ejaculate or a physical stimulus of penis insertion caused remating inhibition for at least 10 days after first mating. Remating frequency at two days after mating was significantly higher in females mated to castrated (spermless) males than in females mated to sham-operated control males. This difference disappeared by day four after mating, indicating that sperm cause a shorter-term inhibition of remating than does a normal first mating. Other factors in addition to sperm must therefore play a role in inhibition of remating.

Journal Article↗

PubMed1999

Messages from mortality: the evolution of death rates in the old.

Ageing is an increase in mortality and/or decline in fertility with advancing age. Evolutionary theories predict that ageing will evolve in response to the pattern of externally imposed hazards to survival and fertility; a prediction confirmed in new empirical studies. Recent studies of large cohorts of experimental animals and of humans have revealed that mortality rates do not continue to accelerate at very advanced ages. It has been suggested that evolutionary theories cannot account for these mortality patterns; however, this challenge is more apparent than real. Heterogeneity between individuals can shape mortality trajectories for populations, and recent evolutionary theory can both account for such heterogeneity and accommodate late-age mortality patterns.

Journal Article↗

PubMed1999

Correlated responses to selection on body size in Drosophila melanogaster.

Correlated responses to artificial selection on body size in Drosophila melanogaster were investigated, to determine how the changes in size were produced during development. Selection for increased thorax length was associated with an increase in larval development time, an extended growth period, no change in growth rate, and an increased critical larval weight for pupariation. Selection for reduced thorax length was associated with reduced growth rate, no change in duration of larval development and a reduced critical larval weight for pupariation. In both lines selected for thorax length and lines selected for wing area, total body size changed in the same direction as the artificially selected trait. In large selection lines of both types, the increase in size was achieved almost entirely by an increase in cell number, while in the small lines the decrease in size was achieved predominantly by reduced cell size, and also by a reduction in cell number. The implications of the results for evolutionary-genetic change in body size in nature are discussed.

Animals↗

PubMed1999

A comparison of the genetic basis of wing size divergence in three parallel body size clines of Drosophila melanogaster.

Body size clines in Drosophila melanogaster have been documented in both Australia and South America, and may exist in Southern Africa. We crossed flies from the northern and southern ends of each of these clines to produce F(1), F(2), and first backcross generations. Our analysis of generation means for wing area and wing length produced estimates of the additive, dominance, epistatic, and maternal effects underlying divergence within each cline. For both females and males of all three clines, the generation means were adequately described by these parameters, indicating that linkage and higher order interactions did not contribute significantly to wing size divergence. Marked differences were apparent between the clines in the occurrence and magnitude of the significant genetic parameters. No cline was adequately described by a simple additive-dominance model, and significant epistatic and maternal effects occurred in most, but not all, of the clines. Generation variances were also analyzed. Only one cline was described sufficiently by a simple additive variance model, indicating significant epistatic, maternal, or linkage effects in the remaining two clines. The diversity in genetic architecture of the clines suggests that natural selection has produced similar phenotypic divergence by different combinations of gene action and interaction.

Animals↗

PubMed1998

Interactions of mating, egg production and death rates in females of the Mediterranean fruit fly, Ceratitis capitata.

Costs of reproduction include costs of producing eggs and of mating itself. In the present study, we made an experimental investigation of costs of reproduction in the Mediterranean fruit fly (medfly, Ceratitis capitata). We demonstrated that virgins live longer than non-virgin females. However, in strong contrast to most findings within the Diptera, non-virginity had no detectable effect on egg production. Therefore the increased longevity of the virgin females cannot be attributed to an increase in egg production in non-virgin females, and instead indicates a cost of mating. A comparison of the life spans of normal females and those sterilized by low doses of X-irradiation, revealed an additional cost of egg production. There were no significant differences in remating levels between females that did and did not lay eggs, showing that the cost of producing eggs is independent of mating frequency. Medfly females therefore suffer a decrease in survival as a result of egg production and of mating, and these costs are independent of one another. To put our results into context, we reviewed the existing literature on the effects of mating on longevity, egg production and sexual receptivity for 64 species of Diptera, and examined the pattern of mating effects that emerged.

Animals↗

PubMed1998

Sex and conflict.

Evolutionary conflict occurs when the deterministic spread of an allele lowers the fitness either of its bearer or of other individuals in the population, leading to selection for suppressors. Sex promotes conflict because associations between alleles are temporary. Differing selection on males and females, sexual selection, and differences in transmission patterns between classes of nuclear and cytoplasmic genes can all give rise to conflict. Inert Y chromosomes, uniparental inheritance of cytoplasmic genes, mating strains and sexes, and many features of sexual behavior may have evolved in part as a result of evolutionary conflict. Estimates of its quantitative importance, however, are still needed.

Alleles↗

PubMed1998

Regulation of gene expression is preserved in aging Drosophila melanogaster.

Aging, and the deterioration of biological performance that characterizes it, are routinely assumed to be due to a progressive global loss of homeostasis and a general increase in dysregulation [1-4] . We tested this hypothesis directly by measuring age-specific variability in gene expression. Analysis of the transcriptional activity of six genes in various inbred lines of Drosophila melanogaster unexpectedly failed to show an increase in variability among individuals as they age and die. Although regulation of gene expression is a central feature of life, a global decline in the control of gene expression does not appear to be either a cause or a consequence of the process of aging.

Aging↗

PubMed1998

Sexual conflict and speciation.

We review the significance of two forms of sexual conflict (different evolutionary interests of the two sexes) for genetic differentiation of populations and the evolution of reproductive isolation. Conflicting selection on the alleles at a single locus can occur in males and females if the sexes have different optima for a trait, and there are pleiotropic genetic correlations between the sexes for it. There will then be selection for sex limitation and hence sexual dimorphism. This sex limitation could break down in hybrids and reduce their fitness. Pleiotropic genetic correlations between the sexes could also affect the likelihood of mating in interpopulation encounters. Conflict can also occur between (sex-limited) loci that determine behaviour in males and those that determine behaviour in females. Reproductive isolation may occur by rapid coevolution of male trait and female mating preference. This would tend to generate assortative mating on secondary contact, hence promoting speciation. Sexual conflict resulting from sensory exploitation, polyspermy and the cost of mating could result in high levels of interpopulation mating. If females evolve resistance to make pre- and postmating manipulation, males from one population could be more successful with females from the other, because females would have evolved resistance to their own (but not to the allopatric) males. Between-locus sexual conflict could also occur as a result of conflict between males and females of different populations over the production of unfit hybrids. We develop models which show that females are in general selected to resist such matings and males to persist, and this could have a bearing on both the initial level of interpopulation matings and the likelihood that reinforcement will occur. In effect, selection on males usually acts to promote gene flow and to restrict premating isolation, whereas selection on females usually acts in the reverse direction. We review theoretical models relevant to resolution of this conflict. The winning role depends on a balance between the 'value of winning' and 'power' (relating to contest or armament costs): the winning role is likely to correlate with high value of winning and low costs. Sperm-ovum (or sperm-female tract) conflicts (and their plant parallels) are likely to obey the same principles. Males may typically have higher values of winning, but it is difficult to quantify 'power', and females may often be able to resist mating more cheaply than males can force it. We tentatively predict that sexual conflict will typically result in a higher rate of speciation in 'female-win' clades, that females will be responsible for premating isolation through reinforcement, and that 'female-win' populations will be less genetically diverse.

Alleles↗

PubMed1998

Behavioural genetics: molecular genetics meets feeding ecology.

Fruit fly larvae occur as either 'rovers', which move a long way to find food, or 'sitters', which stay within a more restricted area. This polymorphism is determined by alleles of a cyclic GMP-dependent protein kinase gene; rovers are at an advantage in crowded populations, while sitters have the edge at low population density.

Alleles↗

PubMed1998

Sex-specific selection on time to remate in Drosophila melanogaster.

Female Drosophila melanogaster were artificially selected for fast and slow time to remate (denoted 'high' and 'low' selection regimes, respectively). Both selection regimes and a control were replicated three times. Correlated responses to selection in females and in males were measured. A significant direct response to selection for time to remating was found in females from both selection regimes. Remating frequency of females showed a correlated response only in the females from the lines selected for faster time to remating. Time to first mating of virgin females showed no correlated response in either selection regime. No correlated response was found in males for time to remate, remating frequency or time to first mating of virgins, indicating that genetic correlations between the sexes do not influence the evolution of these traits in this population of D. melanogaster. There was no direct response to artificial selection for the ability of first males to deter females from remating. However, we found that the genotype of the first male to mate with a female could influence her time to remate; base stock males were better at deterring females from remating than were males from any of the selection lines. Copyright 1998 The Association for the Study of Animal Behaviour.

Journal Article↗