Two mutant alleles of the meiotic locus, mei-9, have been examined for their effect on magnification of a rod Xbb chromosome and transmission of a ring Xbb chromosome under magnifying conditions. Our results indicate that the effects of these two mutations are allele-specific: mei-9a strongly inhibits both rod chromosome magnification and ring chromosome loss under magnifying conditions, while mei-9b has a smaller inhibitory effect on rod chromosome magnification and on the transmission of ring chromosomes under magnifying conditions. These observations can be explained by a difference in leakiness between the two alleles. Our results demonstrate that mutants defective in excision repair and repair replication inhibit ribosomal gene magnification. This suggests that a component of the excision repair pathway is involved in the process of magnification.

A Robertsonian translocation in the mouse between the X chromosome and chromosome 2 is described. The male and female carriers of the Rb(X.2)2Ad were fertile. A homozygous/hemizygous line was maintained. The influence of the X-autosomal Robertsonian translocation on anaphase I non-disjunction in male mice was studied by chromosome counts in cells at metaphase II of meoisis and by assessment of aneuploid progeny. The results conclusively show that the inclusion of Rb2Ad in the male genome induces non-disjunction at the first meoitic division. In second metaphase cells the frequency of sex-chromosomal aneuploidy was 10·8%, and secondary spermatocytes containing two or no sex chromosome were equally frequent. The Rb2Ad males sired 3·9% sex-chromosome aneuploid progeny. The difference in aneuploidy frequencies in the germ cells and among the progeny suggests that the viability of XO and XXY individuals is reduced. The pairing configurations of chromosomes 2, Rb2Ad and Y were studied during meiotic prophase by light and electron microscopy. Trivalent pairing was seen in all well spread nuclei. Complete pairing of the acrocentric autosome 2 with the corresponding segment of the Rb2Ad chromosome was only seen in 3·2% of the cells analysed in the electron microscope. The pairing between the X and the Y chromosome in the Rb2Ad males corresponded to that in males with normal karyotype. Reasons for sex-chromosomal non-disjunction despite the normal pairing pattern between the sex chromosomes may be seen in the terminal chiasma location coupled with the asynchronous separation of the sex chromosomes and the autosomes. The Rb2Ad chromosome can be useful for studies of X inactivation, as a marker for parental derivation of the X chromosome and for mapping loci by in situ hybridization.

Little information exists about the mechanisms that determine the fate of mobile elements in natural populations. In this study we catalogue the distribution of 638 P-elements across 114 X chromosomes in samples drawn from three natural populations of Drosophila melanogaster. There is an extremely high occurrence of elements at the tip relative to the rest of the euchromatic chromosome. We demonstrate that the distribution of de novo insertions of the P-element on a specific laboratory chromosome is markedly different; no P-elements were recovered at the tip in the 243 insertion events recorded. In contrast, insertion data for the π2 chromosome suggests an elevated rate associated with the tip site although it does not appear sufficient to explain the large differential accumulation on wild chromosomes. This raises the issue of inter chromosome (or tip) variation in relative rates, as well as the possibility that rates of elimination are lower at the tip.

The frequency and distribution of P elements were investigated in the third chromosomes of two wild-type strains of Drosophila melanogaster using in situ hybridization of biotinylated probes to the polytene chromosomes. The relationship between these data and the extent of hybrid dysgenesis was determined through assays of egg production, egg hatchability (F2 embryo lethality), snw destabilization and male recombination along the third chromosome. The results suggest that P-element distribution, frequency and structure are all contributory factors in the regulation of hybrid dysgenesis. Texas 6 was shown consistently to be a stronger P strain than Texas 1, eliciting greater reductions in fertility, more extensive snw destabilization and higher frequencies of male recombination. Clustering of male recombination events, arising from pre-meiotic crossing over, was evident among the dysgenic progeny of each strain. Male recombination and snw destabilization were independently distributed among the dysgenic males studied, suggesting that these traits represent separate P-mediated functions. The third chromosome male recombination maps produced by the two strains differed significantly from each other and from the published female meiotic and polytene chromosome maps. Male recombination breakpoints were associated with the original distribution of P sequences in the two strains and the results suggest that this relationship may be closer for potentially complete P factors than for P sequences in general. An analysis of sub-lines derived from individual recombinant males revealed that chromosomal breakpoints could also be associated with novel insertions following P-element transposition.

The study reported here is an examination of the organization and evolution of three Y chromosomal repeated sequences, designated pBC10–0.6, pBC15–1.1, and pBA33–1.8, in five closely related species of the genus Mus. The species distributions of major restriction fragment length polymorphisms produced with a panel of restriction enzymes is used to develop the phylogenetic relationships between the five species studied. However, the apparent degree of relatedness among these species varied a great deal with each of the three probes and was also highly dependent on the particular restriction enzyme used. The usefulness for phylogenetic studies of closely associated sequences varying in evolutionary stability is discussed.

We have surveyed the region of the X chromosome of Drosophila melanogaster which encodes the yellow, achaete and scute genes for restriction map variation. Two natural populations, one from North Carolina, U.S.A. and the other from southern Spain were screened for variation at about 70 restriction sites and for variation due to DNA insertion or deletion events in 120 kilobases of DNA. Mean heterozygosity per nucleotide was estimated to be 0·0024 and 15 large insertions were found in the 49 chromosomes screened. Extensive disequilibrium between polymorphic sites was found across much of the region in the North Carolina population. The frequency of large insertions, which usually correspond to transposable genetic elements, is significantly lower than has been observed in autosomal regions of the genome. This is predicted for X-linked loci by certain models of transposable element evolution, where copy number is restricted by virtue of the recessive deleterious effects of the insertions. Our results appear to support such models. The deficiency of insertions may in this case be enhanced by hitch-hiking effects arising from the high level of disequilibrium.

Segregation of sperm abnormality level and H-2 haplotypes was investigated in F2 hybrid males obtained from reciprocal crosses involving two B10.congenic strains carrying H-2 and the Y chromosome of Japanese wild mice: B10.MOL-OHM (H-2ωm4, 23·1% of sperm abnormalities) and B10.MOL-OKB (H-2ωm8, 11·1% of sperm abnormalities). In both types of crosses mean levels of abnormal spermatozoa were significantly higher for males typed as H-2ωm4/H-2ωm4 than for heterozygous H-2ωm4/H-2ωm8 or homozygous H-2ωm8/H-2ωm8. These results suggest that the gene for high sperm abnormality is linked to H-2 complex of the B10.MOL-OHM strain.

Genome sizes (nuclear DNA contents) were documented spectrophotometrically from individuals of each of nine species of the North American centrarchid (sunfish) genus Lepomis. The distributions of DNA values within and among the nine species were essentially normal and continuous, suggesting that changes in DNA quantity in Lepomis are small in amount, involve both gains and losses of DNA, and are cumulative and independent in effect. Significant differences in mean genome size were found between individuals within populations in all nine species and between species. Nested analysis of variance and comparisons of average genome size difference or distance between individuals drawn from different levels of taxonomic organization revealed that the majority of genome size divergence in Lepomis occurs above the hierarchical level of individuals within populations. The Lepomis data when compared to similar data from North American cyprinid fishes appear to suggest that: (i) genome size evolution in these fishes at least follows a continuous rather than a discontinuous mode; (ii) the general predictions of hypothetical models relating genome size variation as a function of organismal position along adaptive continua may be oversimplified, or not applicable to complex, higher eukaryotes; and (iii) changes in genome size in these fishes may be concentrated in speciation episodes.

Twenty-six strains of mice were tested for their reaction to four different sweet substances; saccharin, acesulfame, dulcin and sucrose. There was considerable strain variation in the degree to which they found the sweet substances preferable to water. The variation in preference for any one sweet substance is very highly correlated with the variation in preference for the other sweet substances. This is interpreted to mean that there is only one sweetness receptor, although an alternative explanation in terms of variation in psychological motivation is not discounted. The difference between C57BL/6Ty and DBA/2Ty is largely due to a single gene, Sac.

Eight mouse mutants with altered charge or activity of lactate dehydrogenase-1 have been detected in offspring derived from mutagen-treated spermatogonia. Using two chromosome-7 marker genes pooled recombination frequencies are estimated as c−14·4±0·8−p−6·9±0·6−Ldh-1.

The recessive tω5-haplotype, a complete haplotype, is transmitted by heterozygous male mice at very high frequencies (> 0·90) in normal matings. The present studies were undertaken to determine the effects of delayed matings and in vitro fertilizations on this phenotypic expression. Males carrying the tω5-haplotype ( + / tω5) were first tested for their frequencies of transmission of the mutant 17th chromosome in both normal and delayed matings. Spermatozoa obtained from these same males were then used to fertilize eggs in vitro. The in vivo and in vitro transmission frequencies were found to be statistically equivalent in all types of inseminations. An in vitro fertilization time course study showed that the same percentages of eggs are fertilized by tω5- bearing spermatozoa when the gametes are coincubated for either 2 or 6 h. The data lead to the conclusion that the transmission frequency of the tω5-haplotype is not affected either by the length of time elapsing between insemination and fertilization or by the environment in which fertilization occurs.

The chromosomal location of the mouse gene coding for vimentin, one of the intermediate filament subunits, was determined by in situ hybridization using specific H3-labelled DNA probes. There is only one copy of the vimentin gene and it is located on chromosome 2 region A2.

A divergent selection experiment with mice, using plasma concentrations of insulin-like growth factor-1 (IGF-1) at 42 days of age as the selection criterion, was undertaken for 7 generations. Lines were not replicated. To obtain sufficient plasma for the IGF-1 assay, blood from four individuals was volumetrically bulked to obtain a litter mean IGF-1 concentration. This necessitated the use of between family selection. Although inbreeding accumulated in a linear fashion in each of the high, control and low lines, the rates were different for each line (3·6, 1·6 and 5·3% per generation for the high, control and low lines, respectively). As a consequence, the effects of selection and inbreeding are confounded in this experiment. Divergence between the high and low lines in plasma concentrations of IGF-1 continued steadily until generation 5. In generations 6 and 7, there was a reduced degree of divergence and this contributed towards the low realized heritability value of 0.15 ± 0.12. Six-week liveweight showed a steady positive correlated response to selection for or against plasma concentrations of IGF-1 until generation 4 (high-low difference = 1·7 g = 12%). In generation 5, a substantial drop in 6-week liveweight in the low line relative to both the high and control lines occurred (high-low difference, 3·9; g, 25%). This difference was maintained until generation 7.

This experiment suggests that genetic variation exists at 6 weeks of age in plasma concentrations of IGF-1 in mice. Furthermore, genetic covariation between plasma IGF-1 concentrations and liveweight at 6 weeks of age is likely to be positive. Further experiments have been initiated to examine these theories.

The th2-haplotype is transmitted at low frequencies (< 0·30) by + / th2 males in normal matings. In the studies described here, the transmission frequency of the th2-haplotype from Rb7 / th2 males was determined for normal and delayed matings and in vitro inseminations. The data show the transmission frequency from the two in vivo inseminations to be less than 0·30 and to be statistically equivalent. However, the in vitro transmission frequency (0·80) is significantly greater than either of the in vivo frequencies. The results show that the environment in which fertilization occurs affects the transmission frequency of this specific t-haplotype significantly.

Nine enzyme activity variants of liver/erythrocyte pyruvate kinase have been found amongst laboratory and wild mice. Four of these variants have been shown by biochemical and immunological criteria to be mutations of the structural gene, Pk-1s. These four structural gene mutations, and two regulatory gene mutations, define the gene complex, [Pk-1]. One allele of the structural gene, Pk-1sl, found in the inbred strain C57BL, has an unusual phenotype and affects the expression of pyruvate kinase in the liver but not erythrocyte. A possible mechanism for this tissue-specific structural gene mutation is suggested.

This paper examines the relation between chromosomal and nuclear-gene divergence in 28 wild populations of the house mouse semi-species, Mus musculus domesticus, in Western Europe and North Africa. Besides describing the karyotypes of 15 of these populations and comparing them to those of 13 populations for which such information was already known, it reports the results of an electrophoretic survey of proteins encoded by 34 nuclear loci in all 28 populations. Karyotypic variation in this taxon involves only centric (or Robertsonian) fusions which often differ in arm combination and number between chromosomal races. The electrophoretic analysis showed that the amount of genic variation within Robertsonian (Rb) populations was similar to that for all-acrocentric populations, i.e. bearing the standard karyotype. Moreover, divergence between the two types of populations was extremely low. These results imply that centric fusions in mice have not modified either the level or the nature of genic variability. The genetic similarity between Rb and all-acrocentric populations is not attributed to the persistence of gene flow, since multiple fusions cause marked reproductive isolation. Rather, we attribute this extreme similarity to the very recent origin of chromosomal races in Europe. Furthermore, genic diversity measures suggest that geographically separated Rb populations have in situ and independent origins. Thus, Rb translocations are probably not unique events, but originated repeatedly. Two models are presented to explain how the rapid fixation of a series of chromosomal rearrangements can occur in a population without lowering variability in the nuclear genes. The first model assumes that chromosomal mutation rates are between 10−3 and 10−4 and that populations underwent a series of transient bottlenecks in which the effective population size did not fall below 35. In the second model, genic variability is restored following severe bottlenecks, through gene flow and recombination.

The behaviour of the X- and Y-borne Sts locus has been studied in male and female mice. There was considerable heterogeneity in STS activity between inbred mouse strains, with a four fold difference in activity between the highest (101/H) and lowest (Ju/Ct) activity strains, which can be interpreted in terms of allelic differences. In all inbred strains male STS levels were higher than those of female STS levels and in the majority of strains tested male STS levels were nearly twice as high as female levels. Reciprocal crosses between C3H/HeH and the STS-deficient substrain, C3H/An, demonstrated that activities of the X- and Y-borne genes in males are essentially the same and this suggested that the lower STS level in females derives from X-inactivation of the locus. The possibility that hormonal differences could instead be responsible for the lower activity in females was ruled out by the findings that (a) castration of males did not reduce their STS levels and (b) sex-reversed males, X / X Sxr, had STS levels typical of females. Final proof that the mouse Sts locus can be subject to the X-inactivation process was provided by the observation that XX females had STS levels that were only slightly (20%) higher than those of XO females. The difference may indicate incomplete inactivation of the locus. Linkage data verifying the location of Sts on the distal end of the X chromosome are provided.

In total, the results of this study show that the murine Sts locus can be subject to the X-inactivation process and this, together with the existence of functional loci of near-equal activities on the X and Y chromosomes, results in an imbalance of STS levels between the sexes. X-inactivation does not therefore serve as a dosage compensation mechanism for the Sts locus in the mouse. All of these findings were made in C3H/HeH mice or in animals carrying C3H/HeH functional Sts alleles, and it is pointed out that the diverse results previously obtained by other investigators may be attributable to their use of different strains and crosses between strains but could also be complicated by technical factors.

Experimentally produced monozygotic twins, natural opposite sex blood chimeras (freemartins), and several pedigrees were used to evaluate the genetic influences on the nucleolus organizer region (NOR) patterns in cattle. In monozygotic twins, the NOR patterns of both twins are extremely similar. In chimeras, NOR patterns of genetically identical, peripheral blood lymphocytes (PBL) from the two partners resemble each other. In contrast, genetically different PBL (sib organ) differ significantly in the same environment. A high heritability of the individual NOR patterns is also demonstrated in our 23 pedigrees. In conclusion, our data demonstrate that variation in NOR expression is predominantly due to genetic factors.

Genetic and morphometric distances between 12 inbred strains of mice ranging from closely related substrains to a sub-species were estimated using published data on single locus polymorphisms, and on the basis of up to 44 measurements on seven different bones, respectively. Simulation was also used to investigate sampling effects for the single loci. There were strong and statistically highly significant correlations among all measures of genetic distance ranging from 0·58 for the comparison of single loci with the logarithm of the Mahalanobis distance based on 24 measurements on four bones, to 0·72 for estimates of genetic distance based on single loci and the morphology of the mandible. These findings are in sharp contrast with those of Wayne & O'Brien (1986) who claimed that ‘structural gene and morphometric variation of mandible traits are uncoupled between mouse strains’. Their failure to find such a correlation is probably because their sample of inbred strains included only a single pair of closely related substrains, and no substrains separated for less than 40 years, and because they failed to correct for non-linearity between morphometric and single-locus measurement scales. Simulations and regression analysis suggested that genetic distances could be estimated with approximately equal precision using morphological data on bone measurements or about 10 cladistically informative single loci, which would usually involve sampling about 50 loci. Data based on single-gene markers is usually more informative than morphometric data for studying the similarity of independently-derived strains. However, similarities among closely related populations such as sublines of an inbred strain can usually be studied more efficiently using morphometry.

Inbreeding experiments in Drosophila, particularly those carried out using the ‘balancer equilibration’ technique, have revealed high levels of inbreeding depression. It has been estimated that non-lethal chromosomes have a fitness of 20% or less in homozygous condition compared to chromosome heterozygotes. Deleterious recessive genes are, in principle, capable of explaining such inbreeding depression. In this paper we have asked quantitatively whether the observed high levels are consistent with what is known about numbers of loci and mutation rates. We find that accepted mutation rates are easily high enough, provided that the deleterious genes are fully recessive. Partial dominance, even to the extent of 10% or less, reverses this conclusion. These calculations have been made assuming the multiplicative model. However the arguments are potentially sensitive to certain types of selective interactions, and a model which proposes quadratic gene interaction allows for higher levels of partial dominance. We also test the effect of taking into account a further constraint. Crow and Mukai have argued from estimates of the persistence of new deleterious mutations affecting viability that heterozygotes have a reduction in fitness of around 1–2% per locus, similar to the estimate for lethal genes. Application of this additional constraint would markedly reduce the range of permissible selection coefficients. However we argue that the selective disadvantages in heterozygotes of most mutations affecting fitness are unlikely to be as high as estimated for mutations affecting viability.