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.

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 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.

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.

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.

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.

Six bacteriophages have been used in the classification of 19 plasmids (antibiotic resistance-mediating R factors and FP sex factors which promote host chromosome transfer) of P. aeruginosa isolated in different geographical regions. On the basis of phage-plating responses on isogenic strains of bacteria differing only in the plasmids carried, five groups of plasmids were distinguishable. In general the groups could be correlated with their geographical origin although differences between plasmids from the same region were found. The unique phage-plating responses were also useful in establishing the possible identity of plasmids isolated from the same original strain and given different designations by independent investigators. The classification of the plasmids derived here on the basis of phage-plating responses could be correlated with classifications based upon other phenotypic characteristics described elsewhere. The nature of inhibition of plating of phages B39 and G101 by R18–1 and R18–3 respectively was shown to be due to interference with some aspect of intra-cellular phage replication rather than to plasmid-mediated restriction.

Mutants of Pseudomonas aeruginosa, which differed in amide growth phenotype from the wild-type strain, were subjected to genetic analysis using the generalized transducing phage F116. The map order of some mutational sites was determined by 3-factor crosses in which a mutation in the linked regulator gene amiR was used as the outside marker to determine the relative order of mutations in the amidase structural gene amiE. Acetamide-positive transductants were recovered in crosses between amidase-negative strains and strains PhB3(PAC377), V2(PAC353) and V5(PAC356) producing mutant amidases which hydrolyse phenylacetamide and valeramide but not acetamide. Some recombinants carried the mutation amiE16 determining the properties of the mutant B amidase produced by strain B6(PAC351) from which both PhB and V class mutants were derived, while other recombinants produced A amidase determined by the wild-type amiE gene.