Mouse populations differing in metabolic rate have been developed through selection for high (MH) and low (ML) heat loss (HLOSS), along with randomly selected controls (MC). Objectives of this study were to (a) compare MH, ML and MC lines for HLOSS and correlated traits of feed intake, body composition and organ weights; (b) compare three widely used inbred mouse lines with MH, ML and MC for the same traits; and (c) investigate potential genotype by diet interaction resulting from feeding diets differing in fat percentage. Heat loss (kcal/day) of MH and ML mice differed by 37% of the mean and remained significant (33%) when HLOSS was expressed on a fat-free mass basis. MH mice consumed more energy than ML with a greater difference in mice fed high-fat compared with standard diets (27% vs 13·9%). Despite greater energy consumption, MH mice were leaner than ML with a difference in total body fat percentage of 40%. The greatest difference in HLOSS between selection and inbred lines was between MH and C57BL/6J (BL), which differed by 26·3%. MH and BL mice also differed in energy intake (15·5%). Body composition of BL mice was similar to MH when fed a standard diet, but similar to ML when fed a high-fat diet. Crosses between MH and ML or between MH and BL would be useful to investigate the genetic regulation of, and identify quantitative trait loci influencing HLOSS, energy intake and body composition. Feeding of a high-fat diet may allow diet-specific loci influencing body composition to be identified in MH and BL lines.

Using second- or third-chromosome substitution lines of Drosophila melanogaster, the genetic variation of inducibility and amylase specific activities in three media (starch, normal and glucose) were investigated. Genetic factors on both the second and third chromosomes were responsible for the variation in amylase specific activity and inducibility. In glucose medium, the genetic variance of amylase specific activity estimated for the second-chromosome substitution lines was larger than that for the third-chromosome substitution lines; however, for starch medium and inducibility, the variance was larger for the third-chromosome substitution lines. High correlations for the second-chromosome substitution lines and low correlations for the third-chromosome substitution lines were observed for amylase specific activities in different media. These results suggest that the genetic factor(s) responsible for inducibility or amylase activity variation in an induced medium such as starch should be on the third chromosome and those in the non-induced medium such as glucose should be on the second chromosome. The functional roles of the factors on the second and third chromosomes would be the repression and induction of amylase, respectively.

I have studied the consequences of habitat patchiness on the persistence times of deleterious alleles in a random mating population. Results based on computer simulations and supported by analytical approximations suggest that deleterious alleles remain approximately 1/(1−2FST) more generations in the patchy than in a comparable homogeneous population, where 0<FST[les ]0·25 is the fraction of genetic variance due to the sample of families across patches in one generation. In natural populations of Drosophila, therefore, the contribution of deleterious mutants to the genetic variance in fitness might be larger than previously thought. A model of density-dependent viability selection, inspired by the suggestion that deleterious effects can substantially increase when the environment becomes harsher, also gives credence to the analytical results and illustrates that mean persistence times are very sensitive to changes in ecological parameters. If the density dependence model can be taken seriously, there is a clear difficulty in comparing observed and expected levels of genetic variance on the basis of the simplest mutation–selection balance model.

Evidence of a large sex-linked effect accounting for 25% of the divergence between mouse lines selected for body weight has been described previously. A marker-based study was undertaken to determine the number and map positions of the putative X-linked quantitative trait loci (QTLs). An F2 population was generated from a reciprocal F1 between an inbred low line derived from the low selection line and the high selection line. To enable inference of marker-associated QTL effects on the X chromosome, an analytical technique was developed based on the multiple regression method of Haley and Knott. The analysis of data on 10 week weight indicated a single QTL of large effect situated at about 23 cM from the proximal end of the chromosome, with a peak LOD score of 24·4. The likelihood curve showed a single well-defined peak, and gave a 95% confidence interval for the QTL location of 8 cM. The estimates for the additive genotypic effects in males and females (half the differences between hemizygous males and between homozygous females) were 2·6 g in both cases, or 17% and 20% of the 10 week body weight in males and females respectively. Dominance effects in the females were found to be non-significant. No significant X-linked effect on carcass fat percentage was detected, but a single X-linked QTL appears to explain almost the entire X-linked body weight effect.

Lines of mice have been divergently selected on one of two traits: (i) estimated fat content at 14 weeks of age, which has resulted in a 5-fold divergence, and (ii) body weight at 10 weeks of age, which has resulted in a 3-fold divergence. Individuals from each line were castrated or sham operated at 10 days of age and subsequently given either exogenous testosterone or the appropriate control from 14 days of age. Castration increased fat content and decreased lean weight in all lines, an effect which was not reversed by administration of testosterone. Body weight was reduced by around 10% as a result of castration and this effect was at least partially reversed by exogenous testosterone. Analysis of body weight, fat content and lean mass at 10 weeks of age failed to detect any interaction between these treatments and genetic background. It is therefore concluded that testosterone metabolism has not contributed disproportionately to the response to artificial selection in spite of its known effects on growth and body composition.

In a QTL mapping study with an F2 population of mice, we have shown that one or more sex-linked factors account for a large part of the divergence between mouse lines selected for high and low body weight. Here, we describe a study undertaken to map the putative X-linked quantitative trait loci (QTLs) by backcrossing segments of chromosome from the high line onto an inbred line derived from the low line, thereby removing possible contributions from the autosomes and linked segments of the X chromosome. Sublines containing a regional at the proximal end of the X chromosome were found to be associated with large differences in body weight, and to account for almost all the difference between the lines. A Markov chain Monte Carlo based multipoint linkage analysis incorporating the available marker and phenotypic information from the backcross pedigree was used to map the QTL to a region of about 6 cM. There was no evidence for QTLs elsewhere on the chromosome. The estimated QTL effect is approximately 20% of mean body weight in males and females at 10 weeks. From results obtained from this study and the accompanying F2 analysis, we conclude the presence of a single factor for body weight localizing to about position (±SE) 26·4±1·2 cM on the X chromosome, which increases body weight by approximately 18% at 10 weeks. A strategy to positionally clone the QTL is discussed.

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.

Levels of neutral genetic diversity in populations subdivided into two demes were studied by multi-locus 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.

It is known that genetic polymorphisms can be maintained in populations without superiority of the heterozygote subject to constant but non-linear selection through periodic and higher-order behaviour. In this paper we explore evolutionary paths from single equilibria to higher-order attractors and the existence of polymorphisms that do not arise from equilibria. We explore whether there is a continuous range of allelic types that can create such polymorphisms. We use a single-locus genetic model with exponential density-dependent fitness functions and show that there are large parameter ranges in regions of both overdominance and partial dominance where polymorphic attractors exist.