There are several instances in which quantitative trait locus (QTL) mapping experiments have been independently carried out for similar traits in different laboratories. We develop a permutation test of the correspondence between the test statistics obtained from genome-wide QTL scans in two such experiments to test whether the same QTLs are segregating in the experimental pair. In simulations, we show that the permutation test has the desired properties if chromosomes are of equal length, but bias can occur if chromosomes are of unequal length, a problem connected with autocorrelation of test statistic values. We apply the test to data from three recent mouse body weight QTL mapping experiments. The results from the test are non-significant, and imply a lack of overall concordance between the QTLs that were segregating in these experiments.

Recent mutation accumulation results from invertebrate species suggest that mild deleterious mutation is far less frequent than previously thought, implying smaller expressed mutational loads. Although the rate (λ) and effect (s) of very slight deleterious mutation remain unknown, most mutational fitness decline would come from moderately deleterious mutation (s ≈ 0·2, λ ≈ 0·03), and this situation would not qualitatively change in harsh environments. Estimates of the average coefficient of dominance (h¯) of non-severe deleterious mutations are controversial. The typical value of h¯ = 0·4 can be questioned, and a lower estimate (about 0·1) is suggested. Estimated mutational parameters are remarkably alike for morphological and fitness component traits (excluding lethals), indicating low mutation rates and moderate mutational effects, with a distribution generally showing strong negative asymmetry and little leptokurtosis. New mutations showed considerable genotype–environment interaction. However, the mutational variance of fitness-component traits due to non-severe detrimental mutations did not increase with environmental harshness. For morphological traits, a class of predominantly additive mutations with no detectable effect on fitness and relatively small effect on the trait was identified. This should be close to that responsible for standing variation in natural populations.

To elucidate the involvement of growth hormone (GH) in the genetic change produced by long-term selection in growth and fatness, a ‘GH knock-out study’ on over 900 mice was undertaken. Lines used had been selected for more than 50 generations for high (PH) and low (PL) body weight (initially protein mass) at 70 d(ays) and for high (F) and low fat content (L) at 98 d, producing a 3-fold difference in body weight and a 5-fold difference in fat content. GH deficiency was achieved by repeated backcrossing into each line a recessive mutant gene (lit) which has a defective GH releasing factor receptor. In the absence of GH, the P lines still differ in body weight (21 d to 98 d): e.g. at 98 d homozygous lit/lit: PH = 24·2 g, PL = 10·0 g; wild-type (wt): PH = 57·4 g, PL = 18·7 g. The effect of the GH deficiency on body weight (untransformed) was very much larger in the PH than in the PL line, but the interaction was much smaller, although still significant, on the log scale. This indicates that changes in the GH system contribute only a small part of the selection response in growth. GH deficiency increased fat percentage in all lines (including P), especially in males (99 d, males lit/lit: F = 26·4%, L = 6·9%; wt: F = 22·0%, L = 4·8%; females: 20·2%, 5·2%, 20·7%, 3·0%) with significant genotype×line and genotype×sex interactions. The interactions between the effects of the lit gene and the genetic background were, however, relatively small compared with these main effects and again indicate that other systems contributed most of the selection response.

Hypertrophied sexually dimorphic eye stalks have evolved independently in several families of Diptera, with the eyespan of males exceeding their total body length in some species. These structures function in intermale contests for territories and in mate attraction, the classical mechanisms of sexual selection. In the family Diopsidae, species with extremely exaggerated eye stalks and marked sexual dimorphism in relative eyespan also usually have strongly female-biased sex ratios in nature caused by X-linked meiotic drive, whereas species with relatively small eye stalks have little or no sexual dimorphism, often lack meiotic drive and have even sex ratios. We investigate the possible connection between sexual selection and sex-ratio meiotic drive by analysing a three-locus model for the evolution of female choice for a male character associated with meiotic drive. Both meiotic drive and the male character are X-linked and the female preference is autosomal. Our model shows that suppressed recombination between meiotic drive and the male character, e.g. by inversion of the X chromosome, is necessary for sex-ratio selection to promote the origin of female mating preferences and exaggerated secondary sexual characters. With complete suppression of recombination, sexual selection reduces the frequency of meiotic drive, and may eliminate it. Very rare recombination, gene conversion or mutation, at rates characteristic of chromosome inversions in Drosophila, restores the meiotic drive polymorphism to its original equilibrium. Sex-ratio meiotic drive may thus act as a catalyst accelerating the origin of female mating preference and exaggerated male traits.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Two new test statistics were constructed to detect departures from the equilibrium neutral theory that tend to produce genealogies with longer internal branches (e.g. population subdivision or balancing selection). The new statistics are based on a measure of linkage disequilibrium between adjacent pairs of segregating sites. Simulations were run to determine the power of these and previously proposed test statistics to reject an island model of geographic subdivision. Unlike previous power studies, this one uses a coalescent model with recombination. It is found that recombination rates on the order of the mutation rate substantially reduce the power of most test statistics, and that one of the new test statistics is generally more powerful than the others. Two suggestions are made for increasing the power of the statistical tests examined here. First, they can be made more powerful if critical values are obtained from simulations that condition on a lower bound for the population recombination rate. Secondly, for the same total length sequenced, power is increased if independent loci are considered instead of a single contiguous stretch.

Fungi normally do not senesce, but in some species mitochondrial plasmids are known to occur that induce senescence. In this paper models for the dynamics of a senescence plasmid in a fungal population are developed and analysed. In the first model it is assumed that total fungal biomass density is constant, while in the second model the resource dynamics and its effect on fungal growth is modelled explicitly. An additional death rate describes the effect of the plasmid on the senescent subpopulation. Plasmids can be transferred to non-senescent fungus. Criteria for the coexistence of the non-senescent and senescent fungal strains are derived, all of which have a clear biological interpretation. It is shown that coexistence is not possible in the first model, but is possible in the second model for a large range of parameter values. We show that the interplay between resource dynamics, fungal growth and plasmid transmission is crucial for coexistence. We develop a biological interpretation of how these mechanisms have to interact to promote coexistence. A numerical study of the second model further clarifies the relations between the numerical value of several parameters and coexistence of non-senescent and senescent fungal strains.

Lysis inhibition is a mechanism of latent-period extension and burst-size increase that is induced by the T4 bacteriophage adsorption of T4-infected cells. Mutants of T4 genes imm, sp and 5 (specifically the ts1 mutant of 5) display some lysis inhibition. However, these mutants experience lysis-inhibition collapse, the lysis of lysis-inhibited cells, earlier than wild-type-infected cells (i.e. their collapse occurs prematurely). Lysis from without is a lysis induced by excessive T4 adsorption. Gp5 is an inducer of lysis from without while gpimm and gpsp effect resistance to lysis from without. This paper shows that interfering with the adsorption of phages to imm-, sp- or 5ts1-mutant-infected cells, in a variety of contexts, inhibits premature lysis-inhibition collapse. From these data it is inferred that wild-type T4-infected cells display resistance to lysis-inhibition collapse by a mechanism resembling resistance to lysis from without.

Similarity between related genomes may carry information on selective constraint in each of them. We analysed patterns of similarity between several homologous regions of Caenorhabditis elegans and C. briggsae genomes. All homologous exons are quite similar. Alignments of introns and of intergenic sequences contain long gaps, segments where similarity is low and close to that between random sequences aligned using the same parameters, and segments of high similarity. Conservative estimates of the fractions of selectively constrained nucleotides are 72%, 17% and 18% for exons, introns and intergenic sequences, respectively. This implies that the total number of constrained nucleotides within non-coding sequences is comparable to that within coding sequences, so that at least one-third of nucleotides in C. elegans and C. briggsae genomes are under strong stabilizing selection.

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.