Pod shattering of rapeseed (Brassica napus) causes serious yield loss. Genetic resistance to shattering has been introgressed into B. napus from B. juncea. This followed from allosyndetic pairing between chromosomes of B and C genomes in the interspecific F1 hybrid, B. juncea × B. napus (2n = 37, AABC). The reconstituted B. napus plant showed regular meiosis with 19 bivalents and had pollen and seed fertility of 84 and 23% respectively. An approach is suggested for achieving introgression from monogenomic diploids to digenomic allopolyploids that exploits non-homologous recombination.

Seventeen highly-inbred lines of Drosophila melanogaster extracted from an M′ strain (in the P/M system of hybrid dysgenesis) were studied for their cytotype and the number and chromosomal location of complete and defective P elements. While most lines were of M cytotype, three presented a P cytotype (the condition that represses P-element activity) and one was intermediate between M and P. All lines were found to possess K.P elements and only eight to bear full-sized P elements. Only the lines with full-sized P elements showed detectable changes in their P-insertion pattern over generations; their rates of gain and of loss of P-element sites were equal to 0·12 and 0·09 per genome, per generation, respectively. There was no correlation between these two rates within lines, suggesting independent transpositions and excisions in the inbred genomes. The results of both Southern blot analysis and in situ hybridization of probes made from left and right sides of the P element strongly suggested the presence of a putative complete P element in region 1A of the X chromosome in the three lines with a P cytotype; the absence of P copy in this 1A region in lines with an M cytotype, favours the hypothesis that the P element inserted in 1A could play a major role in the P-cytotype determination. Insertion of a defective 2 kb P element was also observed in region 93F in 9 of the 13 M lines. The regulation of the P-element copy number in our lines appeared not to be associated with the ratio of full-length and defective P elements.

A male mouse with irregular white spotting, typical of piebald, s, arose during an experiment designed to search for mutations induced in spermatogonial cells by ethylnitrosourea (ENU). On being examined cytologically it was found to carry 40 chromosomes but was effectively XXY since one of the two X chromosomes present was distally fused to a Y chromosome. In common with the previously described XXY mice, all of which carried 41 chromosomes, the mouse was sterile with a total absence of germ cells. Because of this, it was not possible to determine if the white spotting was inherited. The spotting could not be related to any observable abnormality of chromosomes known to carry spotting genes, nor could it be linked in any way with the X and Y fusion. It was concluded from the cytological considerations and the time interval (6 months) that had elapsed between mutagen treatment and birth of the offspring, that whereas the spotting was probably the result of ENU damage in a spermatogonial stem cell, the XY fusion was probably a later and spontaneous event.

I am indebted to Mary Lyon as her X-inactivation hypothesis stimulated my mentor, Barton Childs, and in turn, myself, to think about the consequences of X-inactivation in heterozygous females. I often reread her original papers setting forth the single active X hypothesis, and still marvel at the concise and compelling exposition of the hypothesis and the logical predictions which seemed prophetic at my first reading, and have survived the test of time.

My contribution to this Festschrift reviews evidence derived from studies of DNA methylation, species variation and DNA replication that reveals an important role for methylated CpG islands and suggests a role for late DNA replication in propagating X inactivation from one cell to its progeny. These studies also show that X inactivation is a powerful research tool for identifying the factors which program and maintain developmental processes.

Cross-sectional allometric growth patterns of the cranial and postcranial skeleton were compared between giant transgenic (MT-rGH) mice and their normal littermate controls. Body weights, external body dimensions, and a series of cranial and postcranial linear dimensions of the skeleton were determined for samples of known age. Comparative bivariate and multivariate allometric analyses were completed in order to determine whether (1) the larger transgenic mice differed significantly from the normal controls in aspects of body and skeletal proportions, and (2) any such proportion differences resulted from general allometric effects of overall weight or skeletal size increase. Results demonstrate that the transgenic mice do exhibit significantly different body and skeletal proportions than normal control adults. Allometric comparisons of the skeletal dimensions relative to body weight reveal similar coefficients of growth allometry but several differences in y-intercept values in the transgenic vs. control groups. The comparisons among the skeletal dimensions of the skull and postcranium generally reveal the sharing and differential extension of common growth allometries in the two groups. Thus, the elevated levels of growth hormone (GH) and insulin-like growth factor I (IGF-I) in the transgenic mice appear to result in increased overall growth for the various skeletal elements, but in the relative proportions determined by intrinsic growth controls within that system.

Non-linear offspring-parent regressions and heritabilities are expected for characters showing genetic asymmetry due to directional dominance and/or asymmetrical gene frequencies. Since reproductive fitness characters exhibit these characteristics, they should show consistently nonlinear heritabilities, with greater heritabilities in the direction of lower fitness. As a consequence, responses to bi-directional selection on fitness traits should be asymmetrical in the same direction. This prediction has been tested by an analysis of published bi-directional selection experiments for reproductive fitness traits. Significant asymmetry (24 of 30 studies) in the predicted direction was found. For studies reporting realized heritabilities, the means were 0·173 and 0·259 for lines selected for higher and lower reproductive fitness, respectively, the high lines being 33% less than the low lines. Asymmetry was evident for studies reporting realized heritabilities and for those with random mating controls of the same size as the selection lines. Consequently, it is argued that the asymmetry results from genetic asymmetries. This asymmetry has important implications in the improvement of reproductive fitness traits in plant and animal breeding.

The phenomenon of X-chromosome inactivation in female mammals, whereby one of the two X chromosome present in each cell of the female embryo is inactivated early in development, was first described by Mary Lyon in 1961. Nearly 30 years later, the mechanism of X-chromosome inactivation remains unknown. Strong evidence has accumulated over the years, however, for the involvement of a major switch or inactivation centre on the mouse X chromosome. Identification of the inactivation centre at the molecular level would be an important step in understanding the mechanism of X-inactivation. In this paper we review the evidence for the existence and location of the X-inactivation centre on the mouse X-chromosome, present data on the molecular genetic mapping of this region, and describe ongoing strategies we are using to attempt to identify the inactivation centre at the molecular level.

Spontaneously cycling LT/Sv strain female mice were mated to hemizygous Rb(X.2)2Ad males in order to facilitate the distinction of the paternal X chromosome, and the pregnant females were autopsied at about midday on the tenth day of gestation. Out of a total of 222 analysable embryos recovered, 165 (74·3%) were diploid and 57 (25·7%) were triploid. Of the triploids, 26 had an XXY and 31 an XXX sex chromosome constitution. Both embryonic and extra-embryonic tissue samples from the triploids were analysed cytogenetically by G-banding and by the Kanda technique to investigate their X-inactivation pattern. The yolk sac samples were separated enzymatically into their endodermally-derived and mesodermally-derived components, and these were similarly analysed, as were similar samples from a selection of control XmXp diploid embryos. In the case of the XmXmY digynic triploid embryos, a single darkly-staining Xm chromosome was observed in 485 (82·9%) out of 585, 304 (73·3%) out of 415, and 165 (44·7%) out of 369 metaphases from the embryonic, yolk sac mesodermally-derived and yolk sac endodermally-derived tissues, respectively. The absence of a darkly staining X-chromosome in the other metaphase spreads could either indicate that both X-chromosomes present were active, or that the Kanda technique had failed to differentially stain the inactive X-chromosome(s) present. In the case of the XmXmXp digynic triploid embryos, virtually all of the tissues analysed comprised two distinct cell lineages, namely those with two darkly-staining X-chromosomes, and those with a single darkly staining X-chromosome. Four X-inactivation patterns were consequently observed in this group, namely, (XmXp)Xm, (XmXm)Xp, (Xm)XmXp and XmXm(Xp) in which the inactive X is enclosed in parentheses. The incidence of these various classes varied among the tissues analysed. There was, however, a clear pattern of non-random selective paternal X-inactivation in yolk sac endodermally-derived samples which possessed two inactive X-chromosomes. This finding contrasts with the situation observed in the yolk sac mesodermally-derived and embryonic samples which possessed two inactive X-chromosomes, where the ratio of (XmXm)Xp:Xm(XmXp) was 1:1·20 and 1:1·03, respectively, being clear evidence that random X-inactivation had occurred in these tissues.

The grasshopper Chorthippus parallelus has two quite distinct subspecies, which meet along the Pyrenees forming a hybrid zone. Using silver staining we show that on the French side Cp. parallelus has three nucleolar organizer regions, on the L2, L3 and X chromosomes, while on the Spanish side Cp. erythropus has only two NORs, on the L2 and L3. Laboratory F1 hybrid males show reciprocal differences in the expression of NORs. When a Cp. erythropus is female parent the male progeny show four active NORs in mitotic cells and two silver precipitates in meiotic cells, as expected. But when a Cp. parallelus female donates the X with a NOR, her male offspring have a variable disrupted nucleolar expression. Some NORs are not expressed and extra sites of cryptic rDNA are revealed. Meiosis is more disturbed in this latter F1 cross with higher levels of polyploidy, but both Fls show around 90% spermatid abnormality. Such variation in rDNA expression is also found in individuals collected from the hybrid zone, and the role of this disturbance in affecting fitness is discussed.

A large outbred population of Drosophila melanogaster was subjected to artificial selection on lipid and glycogen storage. In three separate experiments, two replicates underwent sib selection for both increased and decreased storage. In the first study, flies were selected on the basis of total triacylglycerol for ten generations. This experiment resulted in no significant direct response, but there was a significant change in total body weight, underscoring the importance of concern for the allometric relationship between body weight and lipid content. In the second study, selection was performed for 15 generations on the percentage of body composition that was triacylglycerol. A significant direct response was obtained, and the two replicates revealed heritability estimates of 0·40 and 0·43. The third study selected glycogen content for 15 generations, and produced a significant response with heritabilities of 0·25 and 0·31. A series of 12 biochemical and enzyme kinetic traits was examined at five generation intervals in all experiments, and a number of correlated responses were detected. The results are interpreted with respect to the evolutionary constraints on energy storage evolution and the genetic basis of the allometric relationship between body weight and fat content.

Regardless of their origins, functions, and base compositions, all DNAs are scriptures written following the same grammatical rule. At the level of syllables, two, CG and TA are seldom used, while three, TG, CT and CA are utilized with abundance. Accordingly, at the level of three-letter words, two complementary base trimers, CTG and CAG, invariably enjoy frequent usage. Inasmuch as two of the three frequently used syllables, TG and CA are complementary to each other, while two seldom used syllables, CG and TA, are both palindromes, two complementary strands of DNA are inherently symmetrical with each other. Consequently, palindromic sequences as favourite targets of DNA-binding proteins occur at unsuspectedly high frequencies, if they contain TG and CA or CTG and CAG. Nevertheless, there are grammatical rules operating among these high frequency palindromes as well; e.g. the palindromic tetramer TGCA occurs nearly two times more often than its reciprocal; CATG. Thus, DNA-binding proteins are provided with a wealth of abundant targets whose densities are influenced by a regional difference in GC/AT ratios to variable degrees. One palindromic heptamer CAGNCTG is an ideal target of one DNA-binding protein engaged in chromosome packaging and in generation of banding patterns. This heptamer occurs once every 1000 bases in moderately GC-rich sequences, while its incidence is reduced to once every 3000 bases in extremely AT-rich sequences. The above must be the very reason that a solitary human X-chromosome DNA coated with mouse DNA-binding proteins in mouse-man somatic hybrids still maintains the original banding pattern and that the inactive X remains inactive, while the active X remains active.

X/Y male mice carrying the sex reversal factor, Sxr, on their Y chromosomes typically produce 4 classes of progeny (recombinant X/X Sxr ♂♂ and X/Y non-Sxr ♂♂, and non-recombinant X/X ♀♀ and X/Y Sxr ♂♂) in equal frequencies, these deriving from obligatory crossing over between the chromatids of the X and Y during meiosis. Here we show that X/Y males that, exceptionally, carry Sxr on their X chromosome, rather than their Y, produce fewer recombinants than expected. Cytological studies confirmed that X-Y univalence is frequent (58%) at diakinesis as in X/Y Sxr males, but among those cells with X-Y bivalents only 38% showed normal X-Y pseudo-autosomal pairing. The majority of such cells (62%) instead showed an illegitimate pairing between the short arms of the Y and the Sxr region located at the distal end of the X, and this can be understood in terms of the known homology between the testis-determining region of the Y short arm and that of the Sxr region. This pairing was sufficiently tenacious to suggest that crossing over took place between the 2 regions, and misalignment and unequal exchange were suggested by indications of bivalent asymmetry. Metaphase II cells deriving from meiosis I divisions in which the normal X-Y exchange had not occurred were also found. The cytological data are therefore consistent with the breeding results and suggest that normal pseudo-autosomal pairing and crossing over is not a prerequisite for functional germ cell formation. The data support the concept that Y short arm-Sxr pairing and crossing over may be the mechanism responsible for the occurrence of the Sxr variants reported in the literature.

To simplify the description of selection in two environments the terms ‘ antagonistic’ and ‘synergistic’ are used. Selection upwards in a bad environment or downwards in a good environment is antagonistic, the selection and the environment acting in opposite directions on the character. Synergistic selection is the reverse, upwards in a good environment or downwards in a bad, selection and environment acting in the same direction. Published experiments are reviewed to see how well they agree with two expectations. First, Jinks & Connolly (1973) showed that antagonistic selection reduces environmental sensitivity and synergistic selection increases it. The experiments reviewed showed many exceptions to this rule, but they all showed that sensitivity was less after antagonistic than after synergistic selection. This is shown to be simply the consequence of correlated responses being less than direct responses. Second, I suggested (Falconer, 1989) that antagonistic selection might be the best way to improve the mean performance in the two environments. In the experiments reviewed, antagonistic selection was significantly better than synergistic for changing the mean, but it is now shown that there is no theoretical justification for this expectation; if one type of selection is better in one direction the other ought to be better in the other direction.

Expressions are given for the changes of mean performance and of sensitivity resulting from selection in one or other environment; these changes can be predicted from the parameters of the base population. In the experiments reviewed, an increase of mean performance accounted for 49% or more of the upward response. Equations are presented which allow the variance of mean performance, the variance of sensitivity, and the covariance of mean with sensitivity to be derived from parameters estimated in an unselected population, namely the variances in the two environments and the corresponding covariance. The variance of sensitivity that might be ascribed to scale effects is deduced. Directional selection in a single macro-environment is synergistic with respect to the micro-environmental differences, and is expected to increase environmental sensitivity and consequently to increase environmental variance. Stabilizing selection is antagonistic selection in both directions at the same time, and so is expected to decrease environmental variance.

Karyotypic investigation of a phenotypically normal but sterile male mouse showed the presence of an XYY sex chromosome constitution. The synaptic behaviour of the three sex chromosomes was examined in 65 pachytene cells. The sex chromosomes formed a variety of synaptic configurations: an XYY trivalent (40%); an XY bivalent and Y univalent (38·5%); an X univalent and YY bivalent (13·8%); or X, Y, Y univalence (7·7%). There was considerable variation in the extent of synapsis and some of the associations clearly involved nonhomologous pairing. These observations have been compared with previously published information on chromosome configurations at metaphase I from other XYY males.

The parental origin of 3 de novo X-autosome translocations in females with Duchenne Muscular Dystrophy (DMD) was studied by means of methylation analysis using the X-linked probe M27ß. In all three the translocation was found to be paternal in origin. The parental origin of X-autosome translocations in females with and without DMD is compared with other structural abnormalities of the X and with autosomal translocations.