The phenomenon of transposition induction by heavy heat shock (HHS) was studied. Males of a Drosophila isogenic line with a mutation in the major gene radius incompletus (ri) were treated by HHS (37 °C for 1 h followed by 4 °C for 1 h, with the cycle repeated three times) and crossed to untreated females of the same line. The males were crossed 5 d after heat shock, and also 9 d after HHS. Many transpositions were seen in the F1 larvae by in situ hybridization. The rate of induced transposition was at least 2 orders of magnitude greater than that of the control sample, and was estimated to be 0·11 events per transposable element copy per sperm. Two ‘hot’ subdivisions for transpositions, induced probably during the post-meiotic stage of spermiogenesis, were found: 43B and 97DE. Three-quarters of all transpositions were localized in these positions. In other sites the rates of induced transpositions were (1·3–3·2)×10−2 events per occupied segment per sperm, 1 order of magnitude greater than those of the control.

Heart rate in pre-pupae of Drosophila melanogaster is shown to vary over a wide range from 2·5 to 3·7 beats per second. Quantitative genetic analysis of a sample of 11 highly inbred lines indicates that approaching one-quarter of the total variance in natural populations can be attributed to genetic differences between flies. A hypomorphic allele of the potassium channel gene ether-a-gogo, which is homologous to a human long-QT syndrome susceptibility gene (HERG), has a heart rate at the low end of the wild-type range, but this effect can be suppressed in certain wild-type genetic backgrounds. This study provides a baseline for investigation of pharmacological and other physiological influences on heart rate in the model organism, and implies that quantitative genetic dissection will provide insight into the molecular basis for variation in normal and arrhythmic heart function.

In Drosophila melanogaster, male courtship behaviour is genetically controlled and is influenced by sex pheromones. 7-tricosene (7-T) induces a dose-dependent inhibition of male–male courtship, whereas 7,11-dienes stimulate male courtship of females. There is a geographical quantitative variation in the production of two predominant male hydrocarbons, 7-T and 7-pentacosene (7-P). We have previously found that 7-P, the main hydrocarbon from males of West African strains, stimulates males that mainly produce 7-T. Using both ‘natural’ and genetically engineered strains, we find that genetic factors coding for low levels of 7-P in males have co-evolved with factor(s) coding for male responses to high levels of 7-P. These two phenotypes are coded by factors on different chromosomes: the intraspecific polymorphism for the production of 7-T and 7-P is largely controlled by chromosome 2, whereas the variation in courtship towards 7-P-rich males is largely controlled by chromosome 3. The polymorphism of male courtship towards 7-P-rich males shows no correlation with the variation in male responses to female flies.

The murine t complex on chromosome 17 contains a number of homozygous lethal and semi-lethal mutations that disrupt development of the mouse embryo. We recently characterized an embryonic lethality in the rat that results from a germ-line mutation in the tuberous sclerosis 2 (Tsc-2) tumour suppressor gene (the Eker mutation). Remarkably, mouse embryos homozygous for tw8 mutation display cranial defects reminiscent of those observed in rat embryos homozygous for the Eker mutation. To determine whether the Tsc-2 gene, which is in the t complex, is mutated in tw8 or other t haplotypes, we characterized this gene in a series of t haplotype mice. Four Tsc-2 polymorphisms were identified: three in the coding region and one intronic that appeared to be common to all t haplotypes analysed. No evidence was found to argue that the Tsc-2 gene is altered in tw8 haplotype mice. However, in the tw5 haplotype we found a G to T mutation in Tsc-2 that was present only in this t haplotype. In contrast to other polymorphisms within the Tsc-2 coding region which did not result in amino acid changes in Tsc-2 gene product tuberin, this mutation substituted a phenylalanine for a conserved cysteine in tw5 tuberin. Within the t complex, the Tsc-2 gene and the putative tw5 locus appeared to map to different positions, complicating identification of Tsc-2 as a candidate for the tw5 locus and suggesting that the G to T mutation in the Tsc-2 gene may have arisen independently of the tw5 functional mutation.

Patterns of synonymous codon usage are determined by the forces of mutation, selection and drift. We elaborate on previous population genetic models of codon usage to incorporate parameters of population polymorphism, and demonstrate that the degree of codon bias expected in a single sequence picked at random from the population is accurately predicted by previous models, irrespective of population polymorphism. This new model is used to explore the relationships between synonymous codon usage, nucleotide site diversity and the rate of substitution. We derive the equilibrium frequency distribution of weakly selected segregating sites under the infinite-sites model, and the expected nucleotide site diversity. Contrary to intuition, levels of silent-site diversity can increase with the strength of selection acting on codon usage. We also predict the effects of background selection on statistics of synonymous codon usage and derive simple formulae to predict patterns of codon usage at amino acids with more than two synonymous codons, and the effects of variation in selection coefficient between sites within a gene. We show that patterns of silent-site variation and synonymous codon usage on the X chromosome and autosomes in Drosophila are compatible with recessivity of the fitness effects of unpreferred codons. Finally, we suggest that there still exist considerable discrepancies between current models and data.

We examine an analytical model of selection against the deleterious effects of transposable element (TE) insertions in Drosophila, focusing attention on the asymptotic and dynamic characteristics. With strong selection the only asymptotically stable equilibrium point corresponds to extinction of the TEs. With very weak selection a stable and realistic equilibrium point can be obtained. The dynamics of the system is fast for strong selection and slow, on the human time scale, for weak selection. Hence weak selection acts as a force that contributes to the stabilization of mean TE copy number. The consequence is that under weak selection, and ‘out-of-equilibrium’ situation can be maintained for a long time in populations, with mean TE copy number appearing stabilized.

A multilocus stochastic model is developed to simulate the dynamics of mutational load in small populations of various sizes. Old mutations sampled from a large ancestral population at mutation–selection balance and new mutations arising each generation are considered jointly, using biologically plausible lethal and deleterious mutation parameters. The results show that inbreeding depression and the number of lethal equivalents due to partially recessive mutations can be partly purged from the population by inbreeding, and that this purging mainly involves lethals or detrimentals of large effect. However, fitness decreases continuously with inbreeding, due to increased fixation and homozygosity of mildly deleterious mutants, resulting in extinctions of very small populations with low reproductive rates. No optimum inbreeding rate or population size exists for purging with respect to fitness (viability) changes, but there is an optimum inbreeding rate at a given final level of inbreeding for reducing inbreeding depression or the number of lethal equivalents. The interaction between selection against partially recessive mutations and genetic drift in small populations also influences the rate of decay of neutral variation. Weak selection against mutants relative to genetic drift results in apparent overdominance and thus an increase in effective size (Ne) at neutral loci, and strong selection relative to drift leads to a decrease in Ne due to the increased variance in family size. The simulation results and their implications are discussed in the context of biological conservation and tests for purging.

Estimation of variance components with the finite polygenic model (FPM) was evaluated. Phenotypic data for a 6300-pedigree simulated under a wide range of additive genetic models were analysed with constant homozygote difference across loci using deterministic Maximum Likelihood (DML) and a Bayesian method implemented via Gibbs sampling (BGS). Results indicate that under no selection, both DML and BGS accurately estimated the variance components, with a FPM of 5 loci or more. When both analysis methods were applied to equivalent data sets on populations that had undergone selection, the DML method produced upward biased estimates of additive genetic variation and heritability due to its use of pedigree loop cutting, while BGS provided more accurate estimation. BGS was extended to non-additive FPMs with variable homozygote differences and dominance effect across loci. This method was used to analyse data simulated under two genetic models with positive, completely dominant gene action at all loci. Results indicate that the estimates of additive and dominance variances slowly increase as the number of loci in the FPM for analysis increases, while accuracy of predicting individual breeding values and dominance deviations remains unaffected. For the simulated pedigree structure, a FPM with 10 loci or slightly fewer appears to be appropriate for variance component estimation in the presence of dominance.

In dairy cattle, quantitative trait loci (QTL) are usually mapped using the grand-daughter design (GDD), i.e. sets of progeny-tested paternal half-brothers. Linkage information is typically extracted from the segregation of the sire chromosomes amongst their sons. We herein propose to increase the power of a GDD by exploiting the frequently occurring relationship between sires and grandsons which has so far been ignored in most methods of analysis. The proposed approach is a multipoint interval mapping method based on the Wilcoxon sum-of-rank test. Three alternative approaches to combine information from sons and grandsons are evaluated by simulation. In these either (i) sons and grandsons are ranked separately, (ii) sons and grandsons are ranked separately but the sign of the QTL effect is constrained to be the same in both generations, or (iii) sons and grandsons are ranked jointly. The proposed methods have been applied on a real data-set in which a GDD including 907 sons is analysed with a marker map comprising nine microsatellites spanning 46 cM on bovine chromosome 6.