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.

The Luria-Latarjet effect is an increase in resistance of a virus to DNA damage during infection of a host. It has often been assumed to involve recombinational repair, but this has never been demonstrated experimentally. Using nine bacteriophage (phage) T4 mutants, I present evidence indicating that, for phage T4, the Luria-Latarjet effect is due to three repair pathways-excision repair, post-replication-recombinational-repair (PRRR) and multiplicity reactivation (MR) (a second form of recombinational repair). The results also show that the Luria-Latarjet effect develops in two stages. The first stage starts soon after infection. Damage which occurs during the first stage can be repaired by excision repair or PRRR. The second stage appears to start after the first round of DNA replication is complete. DNA damage which occurs during this stage can apparently be repaired by MR as well as the other two repair pathways. The results of this study support the hypothesis that recombinational repair has been selected to ensure that the progeny phage genomes which are packaged have minimum DNA damage. Since other viruses which infect bacterial, animal and plant cells show a Luria-Latarjet effect similar to that in phage T4, the conclusions from this study may have wide applicability.

Bulinus truncatus, one of the intermediate hosts of the genus Schistosoma is an hermaphrodite freshwater snail species occupying a variety of environments over almost all Africa. These environments are subjected to large variations in water availability. B. truncatus is allotetraploid and its populations exhibit various frequencies of aphallic individuals (unable to reproduce as male). Both traits probably favour a reproduction by self-fertilization. Here we investigate the genetic structure of populations of B. truncatus of Niger and Ivory Coast using protein electrophoresis to analyse the influence of the environment and of both the last traits. To obtain an estimate of the true heterozygosity in this allotetraploid species, we analyse independently the two diploid loci at each tetraploid locus. Our study indicates (i) an extremely low intrapopulation polymorphism with most alleles fixed and the total absence of heterozygotes and (ii) low differentiation between populations. These results indicate high gene flow between populations. However, the existence of private alleles sometimes at high frequency, the low polymorphism and the lack of heterozygotes point to the role of both genetic drift and self-fertilization, the second amplifying the genetic consequences of the first.

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.

Linkage disequilibrium between molecular polymorphisms in a 10 kb region in the white locus of Drosophila melanogaster, revealed with a battery of four-cutter restriction enzymes, was investigated in 266 lines sampled from seven natural populations around the world. A total of 73 (35 restriction site, 37 insertion/deletion and 1 inversion) polymorphisms were detected, of which 55 non-unique polymorphisms were analysed for linkage disequilibrium. Clustering of significant linkage disequilibrium was observed in the transcriptional unit of the white locus as in Miyashita & Langley (1988). It was shown that about two thirds of the 2-locus combinations showing significant linkage disequilibrium have similar degree and direction of association over different populations. Despite lower divergence in allelic frequencies of molecular polymorphisms among populations, an increase in the proportion of 2-locus pairs showing significant linkage disequilibrium is observed in the transcriptional unit. Large values of Ohta's D measure ratio (1982 a, b) cluster in the transcriptional unit, and correspond to significant linkage disequilibria. Although the exact molecular mechanism is not clear, these results suggest that epistatic selection is responsible for significant linkage disequilibrium in the transcriptional unit of this locus

Brassica juncea cv. Pusa Bold carrying B. oxyrrhina cytoplasm (oxy cytoplasm) was male sterile and chlorotic under field conditions at low temperature (Prakash & Chopra, 1990). Leaf protoplasts of the chlorotic male sterile alloplasmic line (2n = 36) were fused with hypocotyl protoplasts of green male fertile, B. juncea cv. RLM-198 (2n = 36) using polyethylene glycol. Of the 1043 plants regenerated from 10 fusion experiments, 123 had ‘gigas’ features and were identified as presumptive fusion products. Among field-grown population, one plant was dark green even at low temperatures and male sterile. It possessed 72 chromosomes which formed 36 bivalents at late diakinesis of meiosis-I. This plant was back-crossed to B. juncea cv. Pusa Bold (the maintainer line) for three successive generations. One male sterile, normal green BC3 progeny plant with 2n = 36 was analyzed for organelle constitution. Probing its total DNA with the mitochondrial gene for cytochrome oxidase subunit I revealed that it possessed mitochondria of B. oxyrrhina. Southern hybridization pattern with the gene for ribulose bisphosphate carboxylase oxygenase-large subunit (rbcL) revealed that the chloroplast genome of the chlorophyll deficiencycorrected plant had characteristics of both B. juncea and B. oxyrrhina. The deficiency correction has been attributed to recombination between chloroplast genomes of the two species.

As part of a study to identify dosage-sensitive modifiers of the white eye colour locus and the retrotransposon, copia, a segmental aneuploid screen was conducted. It surveys the autosomal complement of the genome for dosage dependent modifiers of white, including ones effective upon retrotransposon insertion-induced alleles. Several regions were found which, when present as a segmental trisomy, affected one or more of the alleles tested in a strong and consistent fashion. Two of these regions have been identified as containing previously described modifiers, Darkener of-apricot and Inverse regulator-a. The remainder identify new white allele modifiers. Selected segmental monosomics were also tested where possible for regions exhibiting a trisomic effect. At least three regions were found to have a dosage-dependent effect in one, two and three copies.

Three Harwich P sublines with different P-element activity potential were used to investigate the influence of P-derived chromosomes on snω mutability and vg suppression and to relate the induction of these dysgenic traits to the number and structure of P elements. Destabilization of the snω allele, a measure of P transposase activity, was differentially influenced by the major autosomes. Chromosome 2 of the standard Harwich subline, Hw, induced only 60% of the level of mutability relative to chromosome 3, whereas chromosome 3 of the weakest Harwich subline, Hf, induced only 50% of the mutability relative to chromosome 2. In somatic suppression of the vg21–3 allele, chromosome 3 of the Hf subline produced a lower level of complete suppression as compared to chromosome 3 of the Hw or the Hs subline (the high hybrid-dysgenesis-inducing subline). The level of these dysgenic traits and GD sterility, was not correlated with the number of P elements per individual (67–68) or per chromosome arm which was very similar among the sublines. The number of complete P elements per genome, based on Southern blot analysis of the X and major autosomes, ranged from 15 to 19. Destabilization of the snω allele and vg suppression by chromosome 3 was correlated with a greater number of complete P elements. Two novel unexpected observations emerged from these studies: both snω mutability and vg suppression data demonstrated high P-element activity in hybrids derived from non-dysgenic crosses irrespective of Harwich subline, indicating a lack of P-cytotype regulation. Mutability in non-dysgenic males ranged from 40 to 60% of the level found in dysgenic males. The high snω mutability and low GD sterility in non-dysgenic hybrids suggests that these traits may arise by a different mechanism.

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.

The bacterial cell division gene, ftsZ, was used as a specific probe to show the presence of a symbiotic bacterium in two wild type strains of Drosophila melanogaster. Under stringent hybridization conditions we have shown that the bacterium is transferred to the progeny of these strains from infected mothers and can be eradicated by treatment with the antibiotic tetracycline. We have characterized this bacterium, by amplifying and sequencing its 16S rRNA gene, as being a member of the genus Wolbachia, an organism that is known to parasitize a range of insects including Drosophila simulans. In a series of reciprocal crosses no evidence was found that the symbiont causes cytoplasmic incompatibility (CI) which is known to occur in infected strains of D. simulans. The implications of these findings are discussed.

Hitch-hiking of dispersed mobile elements serving as molecular markers was used as a new tool for mapping quantitative trait loci in Drosophila melanogaster. Two Drosophila strains with high fitness (HA) were backcrossed repeatedly to a closely related strain with low fitness (LA) to initiate experimental populations with expected HA gene frequencies of 1/32. The frequencies of 19 insertion sites of the retrotransposons mdg1 and copia were analyzed after 11 to 17 generations. Frequencies of sites from the HA line increased substantially in the pericentromeric region, indicating that one or more loci responsible for the fitness difference between the strains were located there. A maximum likelihood (ML) procedure was applied to estimate selection coefficients associated with the markers, and this indicated a broad, strongly selected region of the chromosome. At least one additional locus was localized in the middle of the 2L arm. Possible applications of this method are discussed.

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.

A novel central partial t haplotype was generated by screening for a recombination event between overlapping distal and proximal partial haplotypes. This haplotype contains just two elements Tcrt and Tcd-3t —involved in the t-specific transmission ratio distortion phenotype. Breeding analysis of males that carry this chromosome provides evidence that Tcd-3 is, indeed, a distorter locus and not a second responder. Furthermore, the data indicate that a single well-defined distorter locus is insufficient to overcome completely the self-destructive, low transmission ratio distortion phenotype expressed by the t allele at the t complex responder locus, although a small, but highly significant, effect was observed.

Studies of lines of mice selected for body mass have shown that there is a significant genetic component affecting this trait although the nature of the genes involved remains to be elucidated. Using replicate lines of mice, our studies have shown that two different variants of the mouse ornithine decarboxylase (ODCase) gene have been selected in replicate lines of mice selected for high and low lean body mass respectively. One variant is associated with an increased peak of ODCase activity in embryos (10–13 days of gestation) in all high mass lines and with a restriction fragment length polymorphism of the expressed gene. The increased ODCase activity coincides with increased ODCase mRNA levels in the high mass selected lines. These results provide evidence implicating ornithine decarboxylase as a major factor in cell growth, and as a candidate ‘trait gene’.

To examine the effects of X-chromosome imprinting during early mouse embryogenesis, we attempted to produce XM0, Xp0, XMXMY, XMXPY and XMXMXP (where XM and Xp stand for the maternally and the paternally derived X chromosome, respectively) making use of mouse strains bearing the translocation Rb(X.2)2Ad and the inversion In(X)1H. Unlike XMXPY embryos, XMXMY and XMXMXP conceptuses suffered from severe growth retardation or abnormal development characterized by deficient extra-embryonic structures at 6.5–7.5 days post coitum (dpc). A cytogenetic study suggested that two XM chromosomes remaining active in certain non-epiblast cells were responsible for the serious developmental abnormality found in these embryos disomic for XM. Although matings involving females heterozygous for Rb(X.2)2Ad hinted at the paucity of XP0 embryos relative to those having the complementary karyotype of XMXMXP, further study of embryos from matings between females heterozygous for In(X)1H and Rb2Ad males did not substantiate this observation. Thus, the extensive peri-implantation loss of XP0 embryos shown by Hunt (1991) may be confined to XO mothers. Taken together, this study failed to reveal a parentally imprinted X-linked gene essential for early mouse embryogenesis other than the one most probably corresponding to the X-chromosome inactivation centre.

The expectation for a gene dose effect in an X-linked phenotype is that the corresponding metrical trait in heterozygous females will lie between values for affected hemizygous males and unaffected males and females. We made sequential measurements (at 30, 60, 90, 120 and 150 days) of serum phosphate concentration and tail length in mice with X-linked hypophosphatemia (genotypes: Hyp/Y, Hyp/+ and Hyp/Hyp) and in their normal litter-mates (genotypes: +/Y, +/+). We also measured renal mitochondrial 25-hydroxyvitamin D3-24-hydroxylase (24-hydroxylase) activity in 5 to 7-month-old mice fed control and low phosphate diets and representing all five genotypes. The animals were obtained by controlled breeding under uniform environmental conditions. The mutant animals all had uniformly and significantly lower serum phosphate levels, shorter tail length and higher 24-hydroxylase activity relative to unaffected litter-mates. There was no evidence of a gene dose effect because values were not significantly different among the three mutant genotypes. We also studied the influence of gamete of origin on serum phosphate, tail length and renal mitochondrial 24-hydroxylase activity in the Hyp/+ offspring of affected males (Hyp/Y) or affected females (Hyp/+ or Hyp/Hyp). We found no effect on the distribution of trait values. We conclude that parental origin of mutant allele does not explain the absence of a gene dose effect in Hyp mice.

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.

This study investigated genetic variation in growth and final size in relationship to differences in heritabilities under good and poor feeding conditions. Heritabilities of growth and final size were estimated for several traits under ad libitum and restricted feeding conditions. A 30% feed restriction from hatching to 44 days of age in Japanese quail chicks decreased body weight and tarsus length at 44 days of age and the length of the third primary covert feather at 24 days of age relative to controls fed ad libitum. Wing length at 44 days of age was not significantly different for ad libitum fed and restricted quail. Genetic variances for body weight and tarsus length were very large throughout growth which resulted in heritability estimates close to one for these traits. The genetic correlations among feeding treatments were low, indicating that different genes were affecting growth under the two treatments. Growth was described by the components: asymptote, growth period, and shape of the growth curve following the modified Richards growth curve model (Brisbin et al. 1986). Tarsus length, which had high heritability of the parameter ‘growth period’ of the model, tended to display a higher heritability under the restriction than under ad libitum feeding. Body weight and feather length, which had either no heritable or low heritable ‘growth periods’ estimates, tended to be more heritable under ad libitum feeding. The shape parameter of the growth curve was not heritable for any trait, except tarsus length under restricted feeding.

In a stably subdivided population with symmetric migration, the chance that a favoured allele will be fixed is independent of population structure. However, random extinction introduces an extra component of sampling drift, and reduces the probability of fixation. In this paper, the fixation probability is calculated using the diffusion approximation; comparison with exact solution of the discrete model shows this to be accurate. The key parameters are the rates of selection, migration and extinction, scaled relative to population size (S = 4Ns, M = 4Nm, Λ = 4Nλ); results apply to a haploid model, or to diploids with additive selection. If new colonies derive from many demes, the fixation probability cannot be reduced by more than half. However, if colonies are initially homogeneous, fixation probability can be much reduced. In the limit of low migration and extinction rates (M, Λ ≪ 1), it is 2s/{1 + (Λ/MS)(1 −exp(−S))}, whilst in the opposite limit (S ≪ 1), it is 4sM/{Λ(Λ + M)}. In the limit of weak selection (M, Λ ≫ 1), it is 4sM/{Λ(Λ + M)}. These factors are not the same as the reduction in effective population size (Ne/N), showing that the effects of population structure on selected alleles cannot be understood from the behaviour of neutral markers.