Karyotype analysis of a series of established mouse embryonic stem cell (MESC) lines showed that the majority were aneuploid by the 7th and 9th passage and that all lines contained a single Robertsonian (Rb) translocation chromosome with a symmetrical, homologous, arm composition Rb(11.11). Although the chromosomal imbalance makes these MESC lines unsuitable for genetic manipulation in vitro and hence for subsequent production of transgenic animals, the spontaneous occurrence and stable retention of the homologous Rb(11.11) as the only metacentric chromosome in an otherwise all acrocentric karyotype, provides potentially useful cell lines for gene assignment and recombinant DNA studies.

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.

The fact that the X-linked genes scurfy (sf) and sparse-fur (spf) of the mouse do not produce a mosaic effect in heterozygotes had been taken, by other workers, together with results from X-Autosome translocations, as evidence that inactivation of the mouse X was incomplete. In this paper it is argued that absence of a mosaic effect is not adequate evidence that a gene is not inactivated. The argument was backed by an experiment in which the spf gene was introduced heterozygously into females carrying an X-linked translocation resulting in non-random X-inactivation with the same X active in all cells. When the mutant (spf) allele was on the active X its effect was fully expressed, indicating that the normal allele on the structurally normal inactive X was undergoing inactivation. Argument is further presented that results from X-Autosome translocations do not indicate the degree of completeness of inactivation in a structurally normal X. Hence, there is no evidence that inactivation of the mouse X is incomplete, although evidence from XO females does suggest that it may be incomplete in man.

A new mutant, Small eyes (symbol Sey), that reduces the size of the eye in the mouse, is described. It is dominant, and lethal when homozygous.

A Mendelian population without artificial external constraints does in general not increase at a constant rate. Formulas neglecting the changes in population size introduce an error which is negligible under ordinary circumstances but whose cumulative effect over long periods may be disastrous. Questions relating to the cost of natural selection, the nature of an unstable equilibrium, the survival of genes, etc. cannot be treated without regard to absolute population sizes. The limitation of the notion of relative fitnesses is illustrated by the fact that in some typical situations the survival of the a-gene depends only on the absolute fitness of the Aa-heterozygote, but not on the fitnesses of the homozygotes. Furthermore, a decrease of the (absolute or relative) fitness of one genotype may actually increase the viability of the population and its ultimate size.

Even when the relative frequency qn of the a-gene tends to zero the absolute number of such genes may increase from generation to generation at a geometric rate. Therefore the circumstance that qn → 0 may be insignificant as compared to the fact that the earth cannot sustain an infinitely increasing population. Ultimately the population size is bound to influence the environment and so the fitnesses will change. Thus we must consider density-dependent fitnesses and then observed fitnesses cannot be used to predict the ultimate fate of a population. It is now known (Dobzhansky, 1965) that relative fitnesses are sometimes very sensitive to small changes in environment and that the same species may occupy a great variety of environmental niches. It is therefore quite likely that at least part of a population will find itself in a modified environment before too many generations have passed. For the evolution of a species and the development of new forms it is then not important that under fixed conditions the relative frequency qn of the a-gene would tend to zero. The problem is whether the actual number of such genes will increase for a period sufficiently long to encounter changed conditions or to establish itself in new combinations. This question is significant because the convergence of the frequencies qn to zero may be extremely slow. Thus even in a population of fixed size a disappearing gene could exist long enough to contribute to evolutionary processes.

Speaking generally, the thinking in terms of an assumed steady state and relative fitnesses seems to aggravate the problem of applying the wonderful results of modern genetics to the theory of evolution. For example, various mechanisms which are often considered as eliminating genetic variability may sometimes produce the opposite effect. The theory of evolution should distinguish between what the physicist would call macroscopic and microscopic equilibrium. Even if the world as we see it were in a perfect equilibrium this would not imply an approximate steady state for individual species, not to speak of genes. It is clear that an evolution to higher forms depends on a frequent decrease in fertility rates. If one considers slow changes rather than an unattainable steady state then a loss of fitness may be beneficial in the long run and contribute to genetic variety.

The effectiveness of the assortative mating of selected individuals in increasing selection response was tested, using abdominal chaeta score in Drosophila melanogaster. Three paired comparisons were made. In two sets of lines with 10 matings per line, individual score was used for selection and as the basis for the assortative mating. In the third set with 20 matings per line an index of individual and family score, designed to maximize rate of response, was used.

The intensity of selection was one in ten in all lines. Flies were raised in vials and individual pedigrees were kept.

In all comparisons, assortative mating gave a greater selection response, this being partly due to a greater realized heritability and partly to a greater selection differential. The effect of the assortative mating was largest in the index selected lines. With random mating, the effectiveness of the index selection itself when compared to individual selection was in accordance with theory.

In two comparisons, assortative mating increased the rate of inbreeding. The highest rate of inbreeding was observed with index selection and assortative mating, even though there were here twice as many matings as in the individually selected lines.

In the individual selection lines, the effective population size was 7·4 pairs of parents, compared to the actual value of 10 and in the index lines 7·0 compared to 20. In the former, only one-half of the matings in the initial generations made any permanent contributions to the line and in the index lines only one-third. Within generations and lines, there was a significant positive correlation between the mean score of a family and its inbreeding coefficient.

It is suggested that assortative mating is a method of increasing selection response in some situations. Its particular characteristic is that it becomes more powerful when the heritability is high whereas all of the other environmental aids to individual selection are more effective when the heritability is low.

The sex-linked gene, brindled, in the mouse produces a coat-colour variegation in heterozygous females. There is much individual variation in the relative areas of mutant and wild-type colour, but it was not known if any of this variation was genetic. The main object, when the experiments were started, was to test the simple expectation of the Lyon hypothesis, that if X-inactivation is random the variegation should not be modifiable by selection. On the assumption that the variegation is due to X-chromosome inactivation, modification by selection would show that the inactivation process, or some property of the derived cell populations, is under genetic control. Heterozygous females were accordingly selected for the area of coat showing the mutant colour. Selection based on individual phenotypes was ineffective, but four cycles of reciprocal recurrent selection based on progeny-means produced a ‘High’ line with 64% mutant area and a ‘Low’ line with 30% mutant area, from a base population with 53% mutant area. Autosomal modifiers were not responsible for the response; the difference between the selected lines was entirely due to properties of the X chromosomes carrying the brindled gene. The changed properties of the X chromosomes were not restricted to the locus of brindled, but extended at least as far as the locus of tabby. The chromosomes carrying the wild-type allele of brindled were not altered by the selection, but normal X chromosomes from other strains affected the degree of variegation. It was concluded that the difference between the selected lines was due either to non-random inactivation or to somatic cell selection. It was not possible to distinguish between these two mechanisms. The results obtained in these experiments with a structurally normal X chromosome were in all essentials similar to those obtained by Cattanach with his X-autosome translocation.

Knobbly, FuKb, a dominant mutation on chromosome 17 of the mouse, causes a kinked tail in heterozygotes and embryonic lethality at about nine days in homozygotes. Abnormal organization of the embryonic ectoderm is first apparent at about embryonic day 7, and the retarded and malformed embryos die by mid 9 days.

Kink, FuKi, a dominant gene that maps in the same region, is also an embryonic lethal in homozygotes; heterozygotes have kinked tails and often a circling gait. We have shown FuKb and FuKi are allelic; the FuKb / FuKi compound dies at the same time as FuKb / FuKb embryos with the same morphological syndrome.

The FuKb phenotype is not seen in offspring in expected ratios. The FuKb males may have a low transmission ratio or penetrance may be incomplete.

An incidental finding of our histological studies is a high incidence of complete twinning when FuKb heterozygotes mate inter se or when FuKb × FuKi matings are made.

The melanotic tumour gene tu-C4 in Drosophila melanogaster shows incomplete dominance, together with variable penetrance and expressivity. It is tentatively located in the region of locus 52–53 on the third chromosome. Tumour formation in mutant homozygotes involves a precocious haemocyte transformation leading to the appearance of lamellocytes at the beginning of the third larval instar. These aggregate to form tumour-like masses which subsequently melanize. The process of tumour formation is in broad outline similar to that found in other tumour strains. Melanotic tumour formation is treated as a dichotomous threshold character, assuming an underlying normal distribution of liability relative to a fixed threshold. The expression of the tumour gene can be influenced by the levels of protein, phospholipid, nucleic acid and carbohydrate in the larval food medium, and changes in dominance and penetrance induced by sub-optimal environments deficient in these nutrients are positively correlated. Reinforcement by selection of the dominance relations of tu-C4 was accompanied by correlated changes in penetrance. Conversely, selection for increased penetrance was accompanied by correlated changes in dominance. Dominance and penetrance, it is concluded, are fundamentally related aspects of tumour gene expression. Recruitment of dominance modifiers linked to the tumour gene was excluded by the mating scheme employed, and the observed changes in dominance relations in response to selection were due largely to modifiers located on the second chromosome. Changes in dominance relations produced by selection could be significantly reinforced, or reversed, by environmental factors and consequently show a substantial genotype – environment interaction effect. These facts are relevant to current theories of dominance evolution.

Two wild-type strains of Coprinus lagopus isolated from a single basidiocarp differ by a factor of two in their basal level of alkaline phosphatase. The gene responsible for this difference is allelic to reg-2 and unlinked to the pho loci; the allele conferring a lower basal level is dominant both in diploids and dikaryons.

Twenty-five population cages of D. melanogaster were set up, each containing a different wild-type second chromosome and the marker chromosome Cy. In all but one case where contamination apparently occurred, the Cy chromosome persisted in the population at high frequency, showing a selective advantage of Cy/ + heterozygotes over wild-type homozygotes. Overall, the results indicate that homozygosity of the entire second chromosome causes a depression in fitness of the order of 85%.

Recently collected strains from Malay peninsula, Taïwan and Japan proved to be similar to previously studied Japanese strains kept for long time under laboratory conditions. It is therefore possible to speak of a Far East race, characterized by slow growth, very high fresh weight and small ovariole number. High heterogeneity between laboratory strains founded from wild caught flies seems also typical. Among the three traits studied, a positive genetic correlation was observed only between duration of development and adult weight. No correlations were found between biometrical traits and the latitude of strain origin. The problem of the origin of the Far East race is discussed.

The genetic control of the sterility of male hybrids between certain laboratory and wild mice (Mus musculus L.) is investigated. The observed sterility is, by definition, hybrid sterility since both parental forms (i.e. wild and laboratory mice) are fully fertile, their male offspring displaying small testes with arrest of spermatogenesis at the stage of spermatogenesis or primary spermatocytes. Results of genetic analysis as well as the failure to detect any chromosomal rearrangements point to a genie rather than a chromosomal type of hybrid sterility.

Fifty-three wild males were classified into three sets, after mating with C57BL/10 inbred females, according to the fertility of their male progeny (set I – only sterile sons; set II – only fertile sons; set III – both fertile and sterile sons). The wild males of set I, which yield only sterile male offspring with C57BL/10 females, sire sterile sons also with females of the following inbred strains: A/Ph, BALB/c, DBA/1, and AKR/J, whereas the same wild males produce fertile offspring with females of C3H/Di, CBA/J, P/J, I/St and F/St inbred strains.

The described hybrid sterility seems to be under the control of several independently segregating genes, one of them (proposed symbol Hst-1) being localized on chromosome 17 (linkage group IX), 6 cM distally from dominant T (Brachyury). A chance to search for the mechanism of hybrid sterility is provided by the finding of two laboratory inbred strains, C57BL/10 and C3H/Di, differing with respect to the Hybrid sterility genetic system only at the Hst-1 gene.

Hst-1 is closely linked but apparently not identical with the sterility factor of recessive t alleles of the T locus.

This paper describes analytical and simulation models of the population dynamics of transposable elements in randomly mating populations. The models assume a finite number of chromosomal sites that are occupable by members of a given family of elements. Element frequencies can change as a result of replicative transposition, loss of elements from occupied sites, selection on copy number per individual, and genetic drift. It is shown that, in an infinite population, an equilibrium can be set up such that not all sites in all individuals are occupied, allowing variation between individuals in both copy number and identity of occupied sites, as has been observed for several element families in Drosophila melanogaster. Such an equilibrium requires either regulation of transposition rate in response to copy number per genome, a sufficiently strongly downwardly curved dependence of individual fitness on copy number, or both. The probability distributions of element frequencies, generated by the effects of finite population size, are derived on the assumption of independence between different loci, and compared with simulation results. Despite some discrepancies due to violation of the independence assumption, the general pattern seen in the simulations agrees quite well with theory.

Data from Drosophila population studies are compared with the theoretical models, and methods of estimating the relevant parameters are discussed.

Cytogenetic studies have ascertained that the segregation of the X-chromosome, during the first meiotic division of the oocyte in XO mice, occurs at random, contrary to the finding of some earlier authors. The ratio of nullo-X to X-bearing oocytes at ovulation does not change with maternal age. The usefulness of the XO mouse as a model for aneuploidy production in women (Lyon & Hawker, 1973) is discussed.

Techniques for isolating and analysing temperature-sensitive mutations in Habrobracon serinopae are presented. The temperature-sensitive patterns and lethal phases are described for nine different mutant strains. Such mutants are well suited for the study of gene action during development.