Haem synthetase activity and co-ordination of α- and β-globin chain synthesis have been investigated in prenatal reticulocytes of congenic FL/4Re +/+ Lvb/Lvb and FL/1 Ref/f Lvb/Lvb, mice, which have a marked hypochromic, microcytic, siderocytic anaemia, with reduced erythrocyte numbers at birth, and also in other stocks bearing the f lesion. Haem synthetase activity in f/f reticulocyte homogenates was similar to that in normal cells but was markedly dependent on protoporphyrin added to the homogenate, while activity in normal cell homogenates was relatively independent of added precursor. In cultured normal prenatal reticulocytes α- and β-globin was synthesized in approximately equal amounts during a 4 h labelling period, but in f/f reticulocytes there was an approximate 50% deficiency in β-globin chain synthesis. This deficiency could be repaired by added haem but not by protoporphyrin. Such a lesion is quantitatively consistent with the observed hypochromia of neonatal f/f erythrocytes. The relationship of this abnormality to effects of the f locus on early erythropoietic precursor cells is discussed.

X-ray-induced mitotic recombination within the lozenge locus of Drosophila melanogaster was found to be non-reciprocal. Recombination was detected by the presence of faceted spots in a smooth (lozenge) eye. Markers were present so that if recombination were reciprocal, equal numbers of vermilion and apricot-vermilion-coloured faceted spots would be formed. Of 19 faceted spots found among more than 60000 eyes examined, 10 were vermilion, 7 variegated (some vermilion and some apricot-vermilion-coloured facets), and 2 probably variegated. None was uniformly apricot-vermilion in colour. Four mechanisms for the formation of faceted spots are discussed: double reciprocal recombination, misrepair or gene conversion before chromatid replication, misrepair or gene conversion after chromatid replication, and misrepair or gene conversion followed by chromosome loss. The evidence most strongly supports the hypothesis that all faceted spots were formed by either misrepair following X-irradiation or gene conversion and were originally vermilion in colour. Subsequent chromosome loss from these vermilion cells led to the production of variegated spots. Variegated spots were generally smaller than those uniformly vermilion in colour, indicating that chromosome loss may occur with greater frequency in older irradiated larvae.

R factors have been demonstrated in multiply drug resistant strains of enterobacteria and Pseudomonas aeruginosa in a Birmingham hospital (Lowbury et al. 1969; Ingram, Richmond & Sykes, 1973). A comparative genetic analysis of these R factors has been initiated on the basis of a variety of phenotypic characteristics. This paper describes the properties of R factors derived from strains which could transfer multiple drug resistance to the recipient species P. aeruginosa, Escherichia coli, Shigella flexneri and Salmonella typhimurium. Two types of R factor could be recognized phenotypically. The single group 1 R factor, R18–1 which is probably the same as RPl-1 (Ingram et al. 1972) was different to the group 2 R factors in many respects, including host range, R factor-specific phage plating, cellular location, drug resistance pattern, and stability. The group 2 R factors were found to be very similar to RPl (Grinsted et al. 1972) and R1822 (Olsen & Shipley, 1973) with respect to their wide host range, plating of a sex specific phage, extrachromosomal location, and drug resistance pattern. Compatibility was shown between the group 1 R factor and a group 2 R factor, providing additional evidence for significant genetic differences.

The age of an allele segregating in a finite population may be defined in two ways. They are (1) the age of a mutant gene that has never reached fixation in the population, and (2) the age including any fixation period in the past. Theoretical expressions for these are derived on the assumption that every mutant is unique.

A study was made of the R factors from two multiply drug resistant wild type isolates of Pseudomonas aeruginosa from a Birmingham hospital (Lowbury et al. 1969) from which, in contrast to other strains from the same source (Chandler & Krishnapillai, 1974a), drug resistance was not transferable to Escherichia coli K12 or Salmonella typhimurium. Transfer of drug resistance occurred at a low frequency to Shigella flexneri, although drug resistance in this species was subsequently non-transferable.

In P. aeruginosa there are several features of these two R factors which distinguish them from the group 1 and 2 R factors described previously (Chandler & Krishnapillai, 1974a). Although coding for resistance to neomycin and tetracycline, they did not express this resistance in two strains of P. aeruginosa examined, in contrast to the wild type strains they were isolated in.

The control of transfer of the two R factors is different to the group 1 and 2 R factors in that derepression of transfer could be demonstrated following physiological treatments or mutagenesis. The R factors of this third group were compatible with the group 2 R factors, but did not repress their pilus synthesis on the basis of R factor specific phage plating.

The genetic relationships of the available second chromosome melanotic tumour mutants in Drosophila melanogaster have been investigated. Complementation tests demonstrate the existence of new alleles of the tu bw locus and show that tu-W and tu-g are alleles. The data suggest that there is a minimum of three major gene loci on the second chromosome involved in tumorigenesis. A number of modifier genes were found which affect the penetrance of the major tumour genes analysed. These and the problems they cause in mapping the low penetrant tumour genes are discussed. It has not been possible to map tu-48a, tu- W and tu-g accurately, due largely to the presence of modifier genes. It appears that the genetic basis for melanotic tumour formation is complex.

The generalized transducing phage F116 has been used to prepare lysates from fast- and slow-growing cultures of Pseudomonas aeruginosa strain 1. These lysates have been used to transduce a number of auxotrophic markers to prototrophy and the ratios of the numbers of transductants obtained with each lysate have been determined. Since the markers are those which have been mapped by conjugation in previous studies it has been possible to compare the ratios obtained for each marker with the relative position of the marker on the chromosome map. If the assumption is made that there is only one circular chromosome in P. aeruginosa strain 1 it is possible to suggest a way in which two apparently unlinked segments might be joined together. It is also possible to suggest that the chromosome replicates sequentially in two directions from a fixed origin.

When a selectively favourable gene substitution occurs in a population, changes in gene frequencies will occur at closely linked loci. In the case of a neutral polymorphism, average heterozygosity will be reduced to an extent which varies with distance from the substituted locus. The aggregate effect of substitution on neutral polymorphism is estimated; in populations of total size 106 or more (and perhaps of 104 or more), this effect will be more important than that of random fixation. This may explain why the extent of polymorphism in natural populations does not vary as much as one would expect from a consideration of the equilibrium between mutation and random fixation in populations of different sizes. For a selectively maintained polymorphism at a linked locus, this process will only be important in the long run if it leads to complete fixation. If the selective coefficients at the linked locus are small compared to those at the substituted locus, it is shown that the probability of complete fixation at the linked locus is approximately exp (− Nc), where c is the recombinant fraction and N the population size. It follows that in a large population a selective substitution can occur in a cistron without eliminating a selectively maintained polymorphism in the same cistron.

The types of equilibria possible with an inversion in a two-locus system are considered, and their stability properties investigated. With complete suppression of crossing-over in inversion heterozygotes, there are three possible types of stable equilibria; which of these is reached by a new inversion depends on the fitness effects of the two loci concerned. With one of these equilibria, basically involving cumulative overdominance of the selected loci, the inverted and standard sequences are genetically homogeneous and differ with respect to both loci. With the other types of equilibrium, the standard sequence remains heterogeneous for one or both loci. It is shown that this situation may lead to variations in karyotypic fitnesses when the inversion is changing in frequency. It is also found that, with certain fitness relationships, two alternative stable equilibria may coexist; the final frequency reached by an inversion may therefore depend on the population's history.

The effects of double crossing-over in inversion heterozygotes were also investigated, and it was shown that the equilibria with double crossing-over are closely related to the corresponding equilibria without it, except that both sequences are more heterogeneous genetically. Within each sequence there is almost complete linkage equilibrium between the selected loci, although both are in linkage disequilibrium with the inversion itself. It was also found that, with double crossing-over, the population tends to remain for many thousands of generations in a state of quasi-equilibrium. In this state, the inversion tends not to return to its original frequency after a perturbation; also, it may remain for a long time relatively homogeneous genetically, especially when rare.

These results were compared with those from experiments and observations on inversion polymorphisms.

Prophage H90 has been found to undergo a phenomenon similar to zygotic induction, during conjugal transfer from a lysogenic donor to a non-lysogenic recipient.

It has not been possible to demonstrate that the level of infectious centres increases concomitantly with transfer of the prophage. However, the genetic consequence of zygotic induction was observed with regard to decreased recombinant yield of markers distal to the prophage. This latter fact has been exploited in interrupted mating experiments, to locate the prophage at between 5 and 7 min on the Pseudomonas aeruginosa strain PAO map. It was further shown by transduction experiments that the prophage does not appear to be linked to clusters of co-transductional markers at the 5 and 7 min locations.

Mutants of Saccharomyces cerevisiae whose colonies were blue when grown on nutrient agar medium containing methylene blue reverted to wild-type with white-colony phenotype at high frequency. This reversion was controlled by nuclear gene suppressors in some mutants, and by cytoplasmic suppressors in others. Each of the latter suppressed several independetly segregating blue mutants. These suppressors could be divided into two classes: suppression by petite mutations which behaved as recessives, and suppression by a cytoplasmic factor in respiration-sufficient cells which behaved as dominant over wild-type but might also be a mutation of rho. A relationship between blue mutation and temperature sensitivity was suggested.

It has been shown previously that, even in the absence of linkage, selection can cause an appreciable change in the genetic variance of a metric character due to disequilibrium; this change is temporary and is rapidly reversed when selection ceases. This result is here extended to allow for the effect of linkage, and it is shown that the change in the variance is effectively determined by the harmonic mean of the recombination fractions. The validity of the approximate general formula derived here has been checked by comparison with exact results obtained from models with five or six loci. In order to determine the likely value of the harmonic mean recombination fraction, a simple model was constructed in which it was assumed that loci are distributed at random along the chromosome maps. Results of computer simulations of this model are reported for different chromosome numbers and numbers of loci.

Pawns are behavioural mutants which show impairment in membrane excitability and are, therefore, devoid of normal avoiding reactions. We obtained 103 lines of Pawns through mutagenesis and screening. Among those that yielded to breeding studies, 59 lines belonged to the pwA complementation group and 38 lines belonged to the pwB group. No other genic loci were found in this extensive analysis. Mutants of the pwA locus showed various degrees of phenotypic leakiness. Based on the pheno- and genotypic differences, we estimated that at least 45 independent mutational events were represented in these 103 Pawn lines.

The amino acid analogues p-fluorophenylalanine (PFP) and ethionine (ETH) are strongly mutagenic in Coprinus lagopus. The most pronounced effect was found with suppressor mutations of the met-1 locus. PFP, at a concentration of 2·4 × 10−4 M, increased the mutation frequency 500 fold and ETH, at a concentration of 2·4 × 10−3 M, 30 fold over the spontaneous mutation frequency. From the spectrum of suppressors of the met-1 locus and the dominant revertants of the ad-82 locus, induced by analogue treatments, it was concluded that both analogues induce single base-change mutations. The dose response curves follow a sigmoid plot, revealing that within a certain range of analogue concentrations, muta-genesis is strongly dose dependent.

Using analogue resistant mutants, it has been shown that PFP mutagenesis is a function of its incorporation into protein. However, ETH mutagenesis is independent of protein incorporation but can be correlated with the degree of ethylation of nucleic acids. The synergistic effect PFP and ETH supports the evidence of the different mutagenic actions of the two analogues.

Position effect variegation has been studied in female mice heterozygous for the flecked X-autosome translocation, T(7; X)Ct. Some of these carried the spotting gene (s) which clarifies the variegated patterns. Others carried a second X-autosome translocation, T(X; 16)16H, which suppresses the randomness of X-chromosome activity.

It was found the position effect variegation stems primarily from early occurring events which lead to the formation of clones of cells with different phenotypes. In this respect the phenomenon appears to parallel that found in Drosophila. However, in the mouse, late-occurring events are also found which can only be readily accounted for by the reactivation of previously inactive loci. They occur, not only during foetal development, but throughout the life-time of the animals and in a manner which suggests they derive from a progressive retreat of the inactivating influence of the heterochromatic X chromosome back along the attached autosome towards the breakpoint. It is proposed that the early occurring events do not lay down fixed programmes of gene suppression, as proposed for Drosophila, but that, like the later-occurring events, they represent the reactivation of previously inactivated loci. The possibility that this might also be true for Drosophila is discussed.

The study also provided evidence favouring the view that the X-chromosome controlling element, Xce, modifies the heterozygous phenotypes of X-linked genes by biasing the randomness of the X-inactivation process, rather than by operating through cell selection mechanisms. The data also support and extend Mintz's (1967) concept of pigment pattern differentiation.

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.

PAM 26, a radiation-sensitive mutant of Escherichia coli strain B, is described. Its properties are attributable to a mutation in a gene, exrB, which is cotransducible with malB. It differs from uvrA (also malB-linked) derivatives of strain B in being sensitive to 1-methyl-3-nitro-1-nitroso-guanidine and γ-radiation, and in being able to reactivate UV-irradiated phage T3. It differs from exrA (also malB-linked) derivatives of strain B in forming filaments during the course of normal growth as well as after irradiation. When exrB was transduced into a K12 (lon+) strain, filaments did not form spontaneously. Three-point transductions established the order of markers as met A malB exrB. Based on an analysis of the frequency of wild-type recombinants in a reciprocal transduction between exrA and exrB strains, it was inferred that they are not isogenic and that the order of markers is malB exrA exrB.

The Colonia isolate of Physarum polycephalum produces plasmodia within amoebal clones. Wheals demonstrated genetically that amoebae of the C50 strain of this isolate, when crossed with heterothallic amoebae, yielded recombinant progeny. He concluded that nuclear fusion and meiosis occurred in these crosses and suggested that nuclear fusion was also involved in plasmodia formation in clones. He thus designated the strain ‘homothallic’.

In the present work genetic evidence is presented which indicates that the Colonia strain CL, when crossed with heterothallic strains, also yields recombinant progeny and thus undergoes nuclear fusion and meiosis. Microdensitometric measurements of nuclear DNA content are reported which indicate that CL amoebae are haploid like heterothallic amoebae, and crossed plasmodia are diploid. However, clonally formed CL plasmodia were found to have the same G2 nuclear DNA content as CL amoebae. This observation excludes the possibility of nuclear fusion when plasmodia form within clones of CL amoebae and therefore the strain cannot be homothallic. Two alternatives, apogamy and coalescence, are proposed as the most likely mechanisms for clonal plasmodium formation in strain CL.

The p6H, p25H, and pbs alleles at the pink-eyed dilution locus in mice (Mus musculus) cause sterility in males and semi-fertility in females when homozygous, while the pd, pun, p, and + alleles do not reduce fertility. Pituitaries from sterile males had significantly lower proportions of gonadotropic cells than pituitaries from fertile males. Ovaries from semi-fertile females contained large numbers of developing follicles, but no corpora lutea or corpora hemorrhagica were found. The proportion of polyovular follicles in ovaries of semifertile females was abnormally high.

Pituitary gonadotropins appear to be reduced in the sterile genotypes although the lesion cannot be localized. Possible relationships between these and other pleiotropic effects of mutant p-alleles are discussed.

Methods have been developed for the selection of mutants resistant to p-fluorophenylalanine, chloramphenicol and actidione. Resistance to p-fluorophenylalanine and to chloramphenicol was inherited as if determined in each case by a single dominant allele present in diploid somatic nuclei. Inheritance of mating type was anomalous in crosses involving drug-resistant mutants. Presumptive mating-type heterokaryons were generated in a few per cent of sexual progeny from a wild-type cross.