This research reports analyses of correlated response in reproductive onset in ICR mice after 23 generations of restricted index selection for divergent body weight gain, early (birth–10 days) or later (28–56 days) in life. Long-term selection altered growth trajectories and 56 day body weight of individuals under different selection regimes in this study. Mice in lines under early selection have the same percentage mature weight at vaginal opening as controls (63%). Vaginal opening is delayed in mice selected for slow early growth, which take longer to reach what appears to be a weight threshold. In contrast, individuals in lines selected for later slow growth undergo vaginal opening at the same age as controls, but at a lower weight and increased percentage mature weight. Pre-compensation or ‘counter-balance growth’ is observed in these lines, with mice selected for late enhanced growth reaching 52% of mature weight at vaginal opening while mice with late slow growth attain 71% of mature weight prior to vaginal opening. Only 42% of mice with late slow growth attain first oestrus by 56 days. We speculate this is a function of growth rate and fat/lean ratio. Mice with early slow growth show compensatory growth, reaching first oestrus at a similar time to controls. We conclude that selection for growth rate has asymmetrically affected reproductive onset, with lines selected for suppressed gains experiencing delays in the reproductive onset traits measured.

Single-locus equilibrium frequencies of a partially recessive deleterious mutation under the mutation–selection balance model are derived for partially selfing autotetraploid populations. Assuming multiplicative fitness interactions among loci, approximate solutions for the mean fitness and inbreeding depression values are also derived for the multiple locus case and compared with expectations for the diploid model. As in diploids, purging of deleterious mutations through consanguineous matings occurs in autotetraploid populations, i.e. the equilibrium mutation load is a decreasing function of the selfing rate. However, the variation of inbreeding depression with the selfing rate depends strongly on the dominance coefficients associated with the three heterozygous genotypes. Inbreeding depression can either increase or decrease with the selfing rate, and does not always vary monotonically. Expected issues for the evolution of the selfing rate consequently differ depending on the dominance coefficients. In some cases, expectations for the evolution of the selfing rate resemble expectations in diploids; but particular sets of dominance coefficients can be found that lead to either complete selfing or intermediate selfing rates as unique evolutionary stable state.

Sponsored by: The Wellcome Trust and B & K Universal Group Limited

Genetic markers throughout the genome can be used to speed up ‘recovery’ of the recipient genome in the backcrossing phase of the construction of a congenic strain. The prediction of the genomic proportion during backcrossing depends on the assumptions regarding the distribution of chromosome segments, the population structure, the marker spacing and the selection strategy. In this study simulation was used to investigate the rate of recovery of the recipient genome for a mouse, Drosophila and Arabidopsis genome. It was shown that an incorrect assumption of a binomial distribution of chromosome segments, and failing to take account of a reduction in variance in genomic proportion due to selection, can lead to a downward bias of up to two generations in the estimation of the number of generations required for the formation of a congenic strain.

A recent paper in this journal by Deng, Li and Li has investigated methods to estimate rates and effects of polygenic mutations using data from mutation accumulation experiments. Here, I evaluate a number of critical points in this paper concerning a maximum likelihood (ML) procedure to analyse mutation accumulation data. I show that Deng, Li and Li's criticisms are based on misunderstandings, or numerical problems they encountered that could have been readily overcome. In Monte Carlo simulations, I show that ML can give a considerable increase in precision over the method of moments that is traditionally used to analyse mutation accumulation data. Furthermore, ML allows the comparison of the fit of different models for the distribution of mutation effects.

In the medaka, Oryzias latipes, the mechanism of sex determination (XX/XY) can be revealed by genetic crosses using a body-colour gene, though it does not have cytologically recognizable sex chromosomes. The recombination restriction of sex chromosomes in heterogametic (XY) males has been demonstrated. To elucidate whether the recombination is prevented by the heterogamety of the sex chromosomes or by maleness, we examined the recombination frequencies among three loci located on the sex chromosomes (r, SL1 and SL2) in heterogametic males (XY), homogametic males (XX and YY), homogametic females (XX) and heterogametic females (XY). The recombination frequencies between r–SL1 and SL1–SL2 were as follows: 0, 0 (XY males); 0, 1·5 (XX males); 1·6% (YY males; 1·2%, 14·4% (XY females); 0·8%, 21·8% (XX females). These results indicate that the recombination restriction of the sex chromosomes in heterogametic males does not result from heterogametic sex chromosomes, but from maleness. Such sex-chromosome-specific recombination restriction in heterogametic sex may have triggered the differentiation of sex chromosomes in vertebrates.

A pair of mutant mice with a first sparse coat appeared spontaneously in the production stock of BALB/c mice with a normal coat. After being sib-mated, they produced three phenotypes in their progeny: mice with normal hair, mice with a first sparse coat and then a fuzzy coat, and uncovered mice. Genetic studies revealed the mutants had inherited an autosomal monogene that was semi-dominant. By using 11 biochemical loci – Idh, Car2, Mup1, Pgm1, Hbb, Es1, Es10, Gdc, Ce2, Mod1 and Es3 – as genetic markers, two-point linkage tests were made. The results showed the gene was assigned to chromosome 11. The result of a three-point test with Es3 and D11Mit8 (microsatellite DNA) as markers showed that the mutation was linked to Es3 with the recombination fraction 7·89±2·19%, and linked to D11Mit8 with the recombination fraction 26·30±3·57%. The recombination fraction between Es3 and D11Mit8 was 32·90±3·81%. It is suggested that the mutation is a new genetic locus that affected the skin and hair structure of the mouse. The mutation was named uncovered, with the symbol Uncv. Further studies showed the mutation affected not only the histology of skin and hair but also the growth and reproductive performance of the mice. The molecular characterization of the Uncv locus needs to be further studied.

Various spatial autocorrelation statistics have been widely used both in theoretical population genetics and to study the spatial distribution of diploid genotypes in many plant and animal populations. However, previous simulation studies have considered only diallelic loci. In this paper, we use a large number of space–time simulations to characterize for the first time the parametric and statistical values of Moran's I-statistics for converted individual genotypes as well as for join-count statistics. A wide range of levels of dispersal and numbers of alleles and allele frequencies are modelled and the results reveal the different general effects of each of these factors on these statistics. We also examine the range of appropriate sampling designs and sizes for which predicted values can be interpolated for specific sampling schemes for any given population genetic field survey. Numbers of alleles and allele frequencies each affect some statistics but not others. The results indicate generally low standard deviations. The results also develop precise and efficient methods of estimating gene dispersal, based on the various autocorrelation measures of standing spatial patterns of genetic variation within populations. The results also extend these methods to loci with multiple alleles, typical of those studied through modern molecular methods.

Quantitative trait loci (QTL) have been identified for competence of the mosquito Aedes aegypti to transmit the avian malaria parasite Plasmodium gallinaceum and the human filarial parasite Brugia malayi. Efforts towards the map-based cloning of the associated genes are limited by the availability of genetic markers for fine-scale mapping of the QTL positions. Two F2 mosquito populations were subjected to bulked segregant analysis to identify random amplified polymorphic DNA (RAPD)-PCR fragments linked with the major QTL determining susceptibility to both parasites. Individual mosquitoes for the bulks were selected on the basis of their genotypes at restriction fragment length polymorphism (RFLP) loci tightly linked with the QTL. Pool-positive RAPD fragments were cloned and evaluated as RFLP markers. Of the 62 RAPD/RFLP fragments examined, 10 represented low-copy number sequences. Five of these clones were linked with the major QTL for P. gallinaceum susceptibility (pgs1), of which one clone mapped within the flanking markers that define the QTL interval. The remaining five clones were linked with the major QTL for B. malayi susceptibility (fsb1), and again one clone mapped within the flanking markers that define the QTL interval. In addition, nine RAPD/RFLP fragments were isolated that seem to be of non-mosquito origin.

Drosophila melanogaster is polymorphic for the major cuticular hydrocarbon of females. In most populations this hydrocarbon is 7,11-heptacosadiene, but females from Africa and the Caribbean usually possess low levels of 7,11-heptacosadiene and high quantities of its position isomer 5,9-heptacosadiene. Genetic analysis shows that the difference between these two morphs is due to variation at a single segregating factor located on the right arm of chromosome 3 near map position 51·5 and cytological position 87C–D. This is precisely the position of a desaturase gene previously sequenced using primers derived from yeast and mouse, and localized by in situ hybridization to the polytene chromosomes of D. melanogaster. Alleles of this desaturase gene may therefore be responsible for producing the two hydrocarbon morphs. Mating tests following the transfer of these isomers between females of the two morphs show that, in contrast to previous studies, the hydrocarbon profiles have no detectable effect on mating behaviour or sexual isolation.

Unconditionally deleterious mutations could be an important source of variation in quantitative traits. Deleterious mutations should be rare (segregating at low frequency in the population) and at least partially recessive. In this paper, I suggest that the contribution of rare, partially recessive alleles to quantitative trait variation can be assessed by comparing the relative magnitudes of two genetic variance components: the covariance of additive and homozygous dominance effects (Cad) and the additive genetic variance (Va). If genetic variation is due to rare recessives, then the ratio of Cad to Va should be equal to or greater than 1. In contrast, Cad/Va should be close to zero or even negative if variation is caused by alleles at intermediate frequencies. The ratio of Cad to Va can be estimated from phenotypic comparisons between inbred and outbred relatives, but such estimates are likely to be highly imprecise. Selection experiments provide an alternative estimator for Cad/Va, one with favourable statistical properties. When combined with other biometrical analyses, the ratio test can provide an incisive test of the deleterious mutation model.

Clines of P-induced hybrid dysgenesis provide a means for monitoring the evolution of transposition repression over space and time. We have studied the molecular and phenotypic profiles of flies taken from a 2900 km cline along the eastern coast of Australia, which had previously been characterized over 10 years ago as having P populations in the north, Q populations at central sites and M′ populations in the south. We have found that Q and M′ populations of flies have increased their range within the cline at the expense of P lines. Q populations were found to be in the north of the cline and M′ populations in the south. Some of the northern Q lines transmit repression through both sexes and type I deletion elements have been isolated from them. We suggest that these elements are responsible for Q type repression. The results support our model that populations made up of Q individuals with strong biparentally transmitted repression form an evolutionarily stable strategy for the repression of hybrid dysgenesis in Drosophila melanogaster.

Variation among males and females in reproductive success is a major determinant of effective population size. Most studies of male mating success in Drosophila, however, have been done under conditions very different from those in typical cultures. We determined the distribution of male mating success in five laboratory populations of D. melanogaster maintained on a 14 d, discrete generation cycle fairly representative of standard Drosophila cultures. Mating success was measured as the number of matings a male could achieve under conditions closely approximating a regular culture vial of these populations. Preliminary studies determined that most mating in these populations occurred within 14 h of the flies attaining sexual maturity. Consequently, individual virgin males were marked with white paint on their thorax, put into vials with varying numbers of unmarked virgin flies of both sexes, and monitored continuously for matings over a period of up to 14 h. At various times during the assay, virgin males and females were added to these vials in proportions simulating the pattern of eclosion in culture vials. The observed variation in the number of matings per male in the five populations was, by and large, consistent with a Poisson distribution, suggesting that male mating success in short-generation-time, discrete-generation laboratory cultures of D. melanogaster may fulfil a fundamental assumption of the Wright–Fisher model of genetic drift in finite populations.

Previous work has shown that genetic diversity at a neutral locus is affected by background selection due to recurrent deleterious mutations as though the effective population size Ne is reduced by a factor that is calculable from genetic parameters such as mutation rates, selection coefficients, and the rates of recombination between sites subject to selection and the neutral locus. Given that silent changes at third coding positions are often subject to weak selection pressures, it is important to develop similar quantitative predictions of the effects of background selection on variation and evolution at weakly selected sites. A diffusion approximation is derived that describes the effects of the presence of a single locus subject to mutation and strongly deleterious selection on variation and evolution at a partially linked, weakly selected locus. The results are validated by computer simulations using the Ito pseudo-sampling method. We show that both nucleotide site diversity and rates of molecular evolution at a weakly selected locus are affected by background selection as though Ne is reduced in the same way as for a neutral locus. Heuristic arguments are presented as to why the change in Ne for the neutral case also applies with weak selection. As in the case of a neutral locus, the number of segregating sites in the population is poorly predicted from the change in Ne. The potential significance of the results in relation to the effects of recombinational environment on molecular variation and evolution is discussed.

An increasing amount of evidence indicates that different forms of environmental stress influence the expression of genetic variance in quantitative traits and, consequently, their evolvability. We investigated the causal components of phenotypic variance and natural selection on the body condition index (a trait often related to fitness in wild bird populations) of blue tit (Parus caeruleus) nestlings under contrasting environmental conditions. In three different study years, nestlings grown under a poor feeding regime attained lower body condition than their full-sibs grown under a good feeding regime. Genetic influences on condition were large and significant in both feeding regimes, and in all three study years. However, although estimates of additive genetic variance were consistently higher in the poor than in the good environment, heritability estimates for body condition index were very similar in both environments due to higher levels of environmental variance in the poor environment. Evidence for weak genotype×environment interactions was obtained, but these contributed little to variance in nestling condition. Directional natural selection on fledging condition of nestlings was detected, and there were no indications of year or environmental effects on the form and intensity of selection observed, in a sample of 3659 nestlings over four years. However, selection on fledging condition was very weak (standardized selection gradient, β=0·027±0·016 SE), suggesting that, in the current population, the large additive genetic component to fledging condition is not particularly surprising. The results of these analyses are contrasted with those obtained for other populations and species with similar life-histories.