The feasibility of using heterozygous tumours induced in hybrids between Snell's isogenic resistant (IR) strains of mice for mutation studies was examined. The system has been described by Mitchison (1956) and Klein, Klein & Révész (1957).

Fourteen hybrid sarcomas (A × A.SW F1; H-2 genotype a/s) were tested in mice of the parental strains. Seven were specific for the original F1 hybrid genotype and failed to give any variants. Four tumours gave variants that were compatible with one of the parental strains. The variants grew progressively in all mice of the parental strain, even in pre-immunized mice, and failed to grow in mice of foreign genotypes. Of these, one tumour, as. 14 gave true variants towards both the parental strains. One tumour, as.7, gave variants regularly in 35·5% of the A.SW mice but only in 7·7% of pre-immunized A.SW mice. It failed to give variants towards the other parental strain.

The effect of triethylenemelamine (TEM) and X-ray treatment on the rate of variant production in hybrid tumours was studied. The effect of the treatment on the viability of tumour cells was first examined by titrating tumour cell suspensions on groups of mice or on the CAMs of groups of developing chick embryos. The TD50 values (50% end-points) were calculated. Comparable results were obtained by titrating on mice and on the CAM, although titration on mice gave more consistent results. Approximately 102 viable, untreated cells were needed to produce a tumour in mice or on the CAM.

Tumour as.7 was tested in the parental strains after treatment with TEM or X-rays. Using comparable cell doses in the untreated controls and treated series, the percentage of variants produced in one of the parental strains (A.SW) was significantly increased after treatment with TEM or X-rays. With the exception of one experiment, no variants were produced in the other parental strain. In one experiment, four variants were produced towards the A strain after treatment with TEM, three of which were tested: only one was found to be specific for the A strain. Three of the A.SW variants, originating after treatment with TEM, were tested: two were specific while one showed incomplete specificity for the A.SW strain. Treatment of specific tumours with TEM or X-rays did not give variants towards either of the parental strains.

Two of the hybrid tumours and their derived variants were examined cytologically. Variants originating spontaneously and after treatment with TEM were examined. While most of the original tumours had chromosome numbers with an exactly diploid modal number, the spontaneous and TEM-treated variants had modal numbers which were hyperdiploid. The TEM-treated variants also had a larger proportion of cells which were triploid or hypotetraploid. This would explain the incomplete specificity of the variants isolated after treatment with TEM.

While it appears possible to use heterozygous tumours for isolating genetical variants specifically compatible with one of the parental strains, the actual nature of the mechanism of variant production remains dubious.

A variant strain of Escherichia coli K12 (♂3) was obtained after ultra-violet irradiation. This strain differs from wild type in the possession of a preferred chromosomal site for the F factor.

When wild-type females are infected with the F factor they are converted to F + males which carry the F factor in the infectious state. These F + males (standard) change with low frequency to Hfr males which carry the F factor on the chromosome. When the variant female (♀3) is infected with the F factor it is converted to an F + male (state II) which changes with high frequency to a specific Hfr male (state I) which carries the F factor at the preferred site (Hfr3).

Male strains carrying the preferred site alternate between the specific Hfr state and the F + state. The mechanism of this alternation is the back-and-forth shift of the F factor between its integrated state of multiplication at the Hfr3 locus and its autonomous state of multiplication. This process is termed episomic alternation.

Episomic alternation offers a physical model for regular changes in state of the gene.

The Hfr3 locus has two allelic forms, high rate of change and standard rate of change. The allele for high rate of change may be considered as a genetic system which occurs in two possible states, state I in which the F factor is present at Hfr3, and state II in which it is not.

(1) Two lines have been selected for small wing cell size from the cage Pacific population. Body size was reduced by about 10% and 15% in the two lines which did not regress when selection was relaxed.

(2) The effects of crossing each line to the unselected population has been determined in a number of repeated tests on the live yeast medium and also on various sub-optimal synthetic media.

(3) The size of the F1, relative to the size of the parents, is greatly influenced by the composition of the larval diet. The F1 may coincide with the mid-parent value but generally significantly exceeds it and is often the same size as the unselected parent population.

(4) In crosses to an unselected population on alternative media the F1 was either the same size as the unselected population or exceeded it.

(5) Crosses between the selected lines produced an F1 which exceeded the larger parent but remained well below the level of the unselected population.

(6) To test for interaction between genes at different loci, chromosomes from the unselected population were substituted in the genetic background of each of the selected lines to provide an array of genotypes in which one, two or three pairs of major chromosomes had homologues derived from different strains. Leastsquares analysis indicated differences between the lines in the distribution of effects among the chromosomes together with the presence of interaction between chromosomes and this was greater for the substitutions in the line which showed the greater consistency of recessive behaviour in crosses to the unselected population.

(7) At the end of the selection experiment two lines were selected for large body size from the F2 of the cross between the two selected lines. Both responded to selection for three to four generations and then fluctuated at a level slightly below that of the unselected population.

(8) The physiological changes which involve correlated changes in body and cell size differ from those which result from selection for smaller body size, at least in the early stages of such selection, and are associated with differences in genetic behaviour. The apparently recessive property, which involves extensive non-allelic interaction, is progressively established during the course of selection. Apparently selection for smaller cell size is particularly effective in disturbing the normal homeostasis of growth and is accompanied by relatively greater loss of heterozygosis than is likely with equivalent reduction in size due to selection for smaller body as opposed to cell size.

All 153 crosses between 18 tomato varieties were grown in F1, F2, F3 and F4. The F2, F3 and F4 were derived by selfing one plant of the previous generation. The F2 plant chosen to give the F3 was selected (1 in 20) for early yield; and the F3 plant chosen to give the F4 was similarly selected. Flowering date was an unsatisfactory character. In crosses segregating for the Mendelian gene ‘uniform’, a significant excess of heterozygotes was selected. The parents transmitted variability of yield (as well as average yield) to their offspring. The division of yield into its components fruit number and fruit size is useful because (1) much of the heterosis in yield can be viewed as a combination effect between these components, (2) the components responded differently to selection, (3) different components showed phenotypic dominance in different directions. The average yield and fruit number responded as expected to selection; fruit size did not. The F1 generation means for all three characters exceeded the parental means; but the crosses were grouped more compactly about their generation mean than were the parents, so that heterosis rarely occurred in crosses involving the best parents. The yields of each cross were analysed into parental main effects (general combining abilities) and interactions (specific combining abilities). No useful prediction of interactions could be made in any generation, either from the same generation in different years or from different generations in the same year. The main effects (general c.a.) were analysed into a part due to regression on parental yield, and a deviation from that regression. No useful prediction of the deviations from parental regression could be made in generations which had responded to selection. The actual advance under selection of different crosses, although not uniform, was unpredictable. During advance under selection, the parental means gave predictions of the (relative) performance of each generation's crosses which were as good as predictions based on the previous generation. This may, of course, be connected with the fact that the parents were inbred and that the amount of heterozygosity decreases in each successive generation. These results indicate, therefore, that in an inbreeding species propagated by seed, the early hybrid generations tell us nothing more than do the parental yields about the relative performance of the inbred lines that can be selected from those hybrids. (This generalization from Lycopersicon esculentum to inbreeders as a whole may, of course, be false.) The relative performance of F1 hybrids, on the other hand, is better predicted from other F1 crosses involving the parents concerned than from the yields of those parents. There was phenotypic dominance of high yield, large fruit number and low fruit weight. The extent of this dominance was not enough to invalidate the analysis by general combining abilities; and since it varied from year to year and from generation to generation, the emphasis that should be given to the top-parent (in contrast to the bottom-parent) in predicting the yields of crosses after selection, is as yet unpredictable.

The meiosis in the F1 hybrid Oryza saliva × O. australiensis was studied. Contrary to the observations of Gopalakrishnan (1959), true allosyndetic bivalents were not found at metaphase I. The most frequent associations were non-chiasmatic, end-to-end pseudobivalents. Autosyndetic bivalents were recorded mostly in the complement belonging to O. sativa, which are distinguishable by their smallness and lighter staining. The meiotic cycle exhibits timing imbalance with earlier condensation, and possibly migration, of the univalents belonging to O. australiensis. The data on meiotic pairing in the F1 hybrid and the comparative morphology of O. sativa, O. officinalis and O. australiensis inicate that the last species is the most primitive member, having originated from the pre-Sativa and pre-Officinalis complex.

The recessive mutant pudgy in the mouse has a greatly shortened vertebral column with highly irregular fusions between vertebrae and fragments of vertebrae. Ribs and sternum are also involved, but the rest of the skeleton is quite normal. The deformities arise from a defective segmentation. Although the paraxial mesoderm forms somite tissue with an epithelially arranged outer layer, this material either shows only an abortive segmentation into somites or, in the tail, none at all. A belated segmentation into dermomyotomes ultimately takes place, but the sclerotomic material remains continuous and gives rise to erratically abnormal blastemata which then chondrify and ultimately ossify.

(1) Fimbriated cells of E. coli K-12 are of two types. In the Fim+ type the expression of fimbriation is susceptible to reversible environmental suppression. This type gives rise to environment-stable mutants termed Fimσ+.

(2) Fimbriated cells can yield two types of non-fimbriated mutant, Fim− and Fimσ−, the latter arising from populations of Fimσ+ cells. Neither type reverts to the fimbriated state.

(3) Both types of fimbriated and non-fimbriated cells can be distinguished by physiological and genetic criteria.

(4) Fimbriation of both types can be transferred to non-fimbriated cells of both types, and segregates among recombinants, in crosses mediated either by transduction or sexual conjugation.

(5) The genetic control of fimbriation involves at least two determinants, for one of which a chromosomal location (fim) has been mapped.

(6) Certain anomalies of fim segregation are interpreted in terms of negative interference over relatively large regions of the bacterial chromosome.

The recurring problem of negative interference in conjugal crosses of Escherichia coli K-12 (Rothfels, 1952; Cavalli-Sforza & Jinks, 1956; Wollman, Jacob & Hayes, 1956) has been periodically overshadowed by new discoveries concerning the mechanism of genetic transfer in this organism, such as unidirectional and partial transfer (Hayes, 1953; Wollman et al., 1956) and the genetic heterogeneity of zygotes formed in F+ × F− crosses (Jacob & Wollman, 1957), which have led to reappraisal of the interpretation of the genetic data. While some of those data (e.g. those of Rothfels, 1952) can be interpreted entirely on the basis of prezygotic elimination of the male genetic contribution, others (e.g. those of Cavalli-Sforza & Jinks, 1956) could not be, and were not, explained entirely on such a basis but demanded the introduction of the notion of incomplete pairing. Meanwhile the problem of negative interference became an important issue in other microorganisms such as bacteriophage, Aspergillus, Neurospora and yeast (review, Pritchard, 1960). The most plausible current model of localized negative interference in these organisms postulates that chromosome pairing is discontinuous and random, and that recombination only occurs within those small regions where pairing is effective (Pritchard, 1955; Chase & Doermann, 1958); thus the ‘coincidence of recombination in two intervals would occur with greater than random frequency if these intervals were short enough and close enough to be frequently included within one effectively paired segment’ (Pritchard, 1960). The mean distance over which such negative interference operates is very small, being of the order of only a few cistrons in both bacteriophage and Aspergillus (Pritchard, 1960).

Sixty-six independently produced markers have been tested for linkage with the A and B mating-type factors. Six loci linked with A and three linked with B were found. Maps of the two linkage groups which include the centromeres were constructed.

Non-identical alleles at two loci, paba-1 and chol-1, were found and crosses between different mutants were used to map the positions of the mutant sites within each locus.

1. The growth of a number of inbred lines from the Pacific cage population have been compared under different conditions of temperature and nutrition. Body size and duration of the larval period were taken as measures of performance. Sub-optimal diets were provided by growing larvae on chemically defined synthetic media.

2. Gene-environment interaction is widespread and often very great. The phenotypic effects of inbreeding on body size, even on a live yeast medium, may be greatly influenced by temperature. In one set of comparisons, inbred lines averaged 20% smaller at 25° C. but only 3% smaller at 18° C.

3. Sub-optimal diets of different chemical composition, which lead to about the same average decline in body size, may differ greatly in the level of heterogeneity of response among the same set of inbred lines. Thus much greater heterogeneity was found on diets deficient in RNA than on diets with low protein levels. Such information is a useful guide to further study of gene-environment interaction in the outbred population.

4. Diets which lead to a decline in body size of flies of the foundation population do not necessarily cause greater proportional decline on the part of inbred lines. Individual lines have been encountered in which body size is quite unaffected by changes in diet which reduce the size of the outbred flies by 25% or more.

5. A series of crosses between lines from the same foundation population showed a striking level of homeostasis. The average body size and development time of the F1's was close to that of the population of flies on the favourable and two alternative sub-optimal diets. Also, compared with the parent lines, there was little evidence of gene-environment interaction among the crosses.

A systematic search for correlations between numerous minor skeletal variants in the mouse showed that these are few in number and feeble in extent. This apparent lack of integration is probably due to the fact that these characters are at the extreme limits of genetical determination and so are overwhelmingly influenced by chance in their manifestation.

A method for obtaining linear estimates of heritability and genetic correlation is given. It is based, essentially, on selecting, from a pedigreed population, prospective parents for which estimates of average genotype and phenotype values are obtained; a regression of genotype on phenotype value is then determined from a straight line fitted through points representing the population mean genotype and phenotype on one hand and the mean genotype and phenotype of selected parents on the other.

The method permits an evaluation of asymmetry in response for a trait selected in both directions, as well as asymmetry in correlated response to selection of two different traits, with data from a single pedigreed population.

1. Antigenic polymorphism between individuals of the subspecies Peromyscus maniculatus gracilis is demonstrated.

2. Absorption analysis of heteroimmune rabbit sera using erythrocytes of individual mice revealed two unitary complete (saline) agglutinins, designated as anti-A and anti-B, reactive to erythrocytic antigens in this species.

Isoimmunization apparently demonstrated these same antigenic differences.

3. The two antigenic characters (A and B) defined by the agglutinins are inherited as if simply related to allelic factors designated PmA and PmB respectively.

4. These two antigens are found in representatives of both the subspecies P. m. gracilis and P. m. bairdii, and, in addition, the A antigen was observed in a laboratory stock of P. polionotus. Tested individuals of the species P. leucopus and Mus musculus, however, possessed neither antigen, and samples of human blood also lacked both antigens.

5. Species-specific agglutinins distinguishing individuals of the species P. leucopus and P. maniculatus, and population-specific agglutinins which distinguished between individuals of the subspecies P. m. bairdii and P. m. gracilis, have been observed.

A modest theory of polygene selection is presented. Recently published data show that the curved model of gene action (presented in a previous paper) is insufficiently general. The curved model does, however, show that the scaling tests (used in the additive type of polygene analysis) do not guarantee additivity; they guarantee a state of indeterminacy, in which additivity is one of a range of reasonable possibilities. These different possibilities give entirely different predictions of selective advance. The failure (in practice) of polygene analysis does not reduce the value of polygene concepts.