Lines of mice have been divergently selected for over forty generations on either body weight or fat content. Reciprocal crosses were made between the divergent lines and the offspring backcrossed to the parental lines. The resulting data allowed us to investigate the genetic basis of response, including two features of particular interest: (i) the relative contribution of autosomal and sex-linked genes and whether any significant Y chromosome or cytoplasmic effects were present (ii) the mechanism of gene action, whether predominantly additive or whether significant dominance effects were present. A large additive sex-linked effect was observed in lines selected on body weight which accounted for approximately 25% of the divergence. The remaining 75% of the divergence appeared to be autosomal. There was no apparent sex-linked effect in lines selected on fat content and the response appeared to be entirely autosomal and additive.

Gene action underlying selection responses has been studied using crossbreeding. Maximum likelihood based segregation analysis has been presented for analysing backcross data for the presence of genes with a large effect. Two sets of divergently selected lines (P-lines for body weight and F-lines for fat content) were reciprocally crossed and the F1s were crossed to the high and low lines to produce all possible backcrosses. Earlier analysis had shown that the difference in body weight at 10 weeks (n = 595) between the high and low P-lines was largely (75–80%) explained by autosomal, additive genes with the remainder explained by additive genes on the X chromosome. Maximum likelihood segregation analysis suggested the presence of a major effect on the X chromosome, but as there was only one round of recombination between the X chromosomes in the forming of the backcrosses, linked genes on the X chromosome could have acted together to give the appearance of a single major gene. The difference in fat content between the F-lines (n = 578) could be explained by autosomal genes of largely additive effect. Segregation analysis suggested the presence of a major gene with complete dominance, but this was attributed to a relationship between the mean and the variance: transformation of the data resulted in only polygenic additive genes being of importance. This study concluded that maximum likelihood based analysis and crosses between selected lines provide a powerful means for studying the gene action underlying responses to selection.

Previous studies have demonstrated that the LT/SvKau strain of mice ovulates a high proportion of oocytes as diploid primary oocytes rather than secondary oocytes. These ovulated primary oocytes are arrested at meiotic metaphase I but may be fertilized to produce digynic triploid embryos. In the present study, 40·4% of eggs analysed from LT/SvKau females were ovulated as primary oocytes, compared to 1·2% from control C57BL/Ws strain mothers. These two inbred strains were intercrossed to produce eight sets of Fl, F2 and backcross females and the frequency of triploidy was investigated. The results are compatible with segregation of a co-dominant, autosomal gene that has a major influence on the incidence of triploidy. We suggest that the provisional gene symbol Poo (primary oocyte ovulation) be assigned to this gene, with alleles Pool (the ‘mutant’ allele present in the LT/SvKau strain) and Poob (the normal allele present in C57BL/Ws mice). Poo is incompletely penetrant and has variable expressivity because the proportion of oocytes ovulated as primary oocytes by LT/SvKau mice was variable and, in some cases, nil. In putative Pool/Poob heterozygotes the frequency of ovulated primary oocytes was increased only marginally (from 1·2% to 66%) by the presence of one copy of the Pool allele, but this increase was found consistently (in two reciprocal Fl crosses) and was statistically significant. No evidence was found for tight genetic linkage between Poo and two Mendelian loci (brown on chromosome 4 and glucose phosphate isomerase on chromosome 7), that were segregating in the crosses. The Pool mutant in the LT/SvKau strain of mice provides a valuable resource to study the cell and molecular biology of mammalian oocyte maturation and the control of meiosis.

A method was developed to estimate effects of quantitative trait loci (QTL) by maximum likelihood using information from changes of gene frequency at marker loci under selection, assuming an additive model of complete linkage between markers and QTL. The method was applied to data from 16 molecular and coat colour marker loci in mouse lines derived from the F2 of two inbred strains which were divergently selected on 6-week weight for 21 generations. In 4 regions of the genome, marker allele frequencies were more extreme than could be explained by sampling, implying selection at nearby QTL. An effect of about 0·5 standard deviations was located on chromosome 11, and accounted for nearly 10% of the genetic variance in the base population. QTL with effects as small as 0·2 phenotypic standard deviations could be detected. For typing of a given number of individuals, the power of detection of QTL is very high compared to, for example, analysis of an F2 population. The joint effects of linkage and selection were investigated by Monte Carlo simulation. Marker gene frequencies change little as a consequence of selection at a QTL unless the marker and QTL are less than about 20 cM apart.

Ybb− is an rDNA-deficient chromosome of Drosophila that has often been used in magnification experiments to induce high-frequency reversion of bobbed (bb) chromosomes. We observed previously that Ybb− causes ring chromosome loss even when the rings are bb+, suggesting that Ybb− induces magnifying sister chromatid exchanges in bb+ rings. Here we show that the Ybb- chromosome causes low levels of bb magnification in bb+ flies. We refer to the ability of Ybb− to bypass the rDNA deficiency requirement for magnification as ‘constitutive’ magnification. We have magnified the ribosomal genes on the Ybb− chromosome and analysed the revertant chromosomes using genetic and molecular methods. We find that magnified Ybb− chromosomes also exhibit constitutive magnifier activity. Molecular analysis shows that both type 1 and type 2 intron+ ribosomal gene repeats are associated with magnified Ybb− chromosomes. Type 2 introns have been described previously in the rDNA of both X and Y chromosomes. However, type 1 intervening sequences are thought to be present only in X, but not Y, ribosomal genes. Some of the Ybb− type 1 insertions differ from those present in the rDNA of X chromosomes in that they contain an EcoRl site, and some may be present in tandem arrays. The constitutive magnifier activity of Ybb− may reside either in the structurally unusual ribosomal gene intervening sequences associated with the chromosome, or in the locus on YL that is required for magnification to occur.

Selection for increased and decreased ratio of eye span to body length was exerted on male stalk-eyed flies (Cyrtodiopsis dalmanni) from Malaysia using replicate selected and unselected lines. Response to selection was symmetrical. After 10 generations high line male eye span increased to 1·3 body lengths while low line male eye span declined to 1·1 body lengths. Realized heritabilities for eye span to body length ratio, estimated using regressions of deviations from unselected controls on cumulative selection differentials, were greater than zero for all four selected lines with average h2 = 0·35 + 0·06. The static linear allometric relationship between eye span and body length diverged between selected lines and rotated among selected line males in the same direction as among males in other sexually dimorphic diopsid species. Crosses between lines after 13 generations of selection indicate that the genes which influence relative eye span combine additively and do not exhibit sex linkage or maternal effects. The genetic correlation between the sexes, 0·29 + 0·05 as estimated by the regression of female on male change in eye span, did not prevent sexual dimorphism in eye span from diverging between lines. These results suggest that the exaggerated eye span of male C. dalmanni is maintained by natural selection opposing sexual selection rather than by lack of or asymmetry in additive genetic variation. Furthermore, the variation in sexual dimorphism for eye span-body length allometry observed among extant diopsid species is consistent with sexual selection of variable intensity acting on relative eye span.

Three tests of neutral theory were carried out using a large dataset of vertebrate allozyme studies. The first test considered the relationship between the mean and variance of single locus heterozygosity across a sample of enzymes and non-enzymatic proteins. The second test compared the distributions of heterozygosity between paired proteins in balanced datasets in which each protein is scored for the same sample of species. The third test compared the observed distribution of single locus heterozygosity with theoretical distributions predicted by neutral theory. The results show an excellent quantitative fit with the predictions of neutral theory, though some small deviations from neutrality were observed which are consistent with the action of natural selection.

For a population undergoing mass selection, derived from an unselected base population in generation zero, the expected long-term contribution to the population of an ancestor from generation 1 was shown to be equal to that expected during random selection multiplied by (where is one half the breeding value of the ancestor for the trait under selection standardized by the phenotypic standard deviation, i the intensity of selection, and is the competitiveness which is defined by the heritability in generation 2 and k the variance reduction coefficient). It was shown that the rate of inbreeding (ΔF) could be partitioned into three components arising from expected contributions, sampling errors and sampling covariances respectively. Using this result ΔF was derived and shown to be dominated by terms that describe ΔF by variance of family size in a single generation plus a term that accounts for the expected proliferation of lines over generations from superior ancestors in generation 1. The basic prediction of ΔF was given by

where M and F are the numbers of breeding males and females, T the number of offspring of each sex, ρm and ρt are correlations among half-sibs in generation 2 for males and females respectively, and K is a function of the intensity and competitiveness.