1. An auxotroph of Salmonella typhimurium, pro-401, was isolated in a strain that was unstable at the su-leuA locus. The auxotrophy of pro-401 is probably due to the attachment of a controlling episome to the proline region of the genome where it suppresses gene expression.

2. The controlling episome frequently transposes over short distances so that all clones consist of cells, mixed for the site at which the controlling episome is attached; homologous transductions yield prototrophs.

3. The controlling episome can transpose to a different complementation group; homologous transductions yield abortive transductants; syntrophism occurs between cells that are ‘mutant’ in different complementation groups to give reversions consisting entirely of auxotrophic cells which are called auxotrophic reversions.

4. The controlling episome transposes over very short distances and never to beyond the limits of this proline region of the genome; no wild-type reversions were found.

5. The controlling episome can be located at relatively distant proline sites in different clones; prototrophs from transductions between clones that are separated by many subculturings can be 100 times more frequent than from homologous transductions.

6. The controlling episome has its frequency of transposition to different complementation groups increased by UV; irradiation increases the frequency of auxotrophic reversions.

7. The controlling episome continues to transpose in stored cells.

8. The pattern of reversions of pro-401 is different in these studies from its pattern two years previously. This is discussed.

1. The rate of production by X-rays of new genetic variation in two quantitative characters in Drosophila melanogaster (sternital and sternopleural bristles) has been investigated, using ‘plateaued’ populations which had reached the limit under artificial selection and, for sternital bristles only, populations which had been made genetically invariant by inbreeding. The genetic variation was always measured by the response of the population to selection. The X-rays dose given in any generation was always 1800 r. to adults.

2. Seven plateaued lines had eight cycles of alternate irradiation and selection, each with its non-irradiated control. All the responses were small but in three lines they were significantly greater after irradiation.

3. Selection was applied to three different inbred lines, genetically marked to detect contamination, after varying periods of irradiation. At the same time, the inbred lines and lines derived from them which had been mass mated in bottles were selected. The irradiated populations showed a greater response. The new genetic variance produced by the irradiation was approximately 10−5 units/r. The estimate of the dose required to introduce new variation equal to that in a standard outbred population was 500,000 r.

4. The effective population size was an important factor in the interpretation of some of these results on the long-term effects of radiation. By observing the variation between replicate lines in the frequency of a gene with a visible effect under these culture conditions (i.e. in a single culture bottle) the effective population size was estimated at sixty. Outbred populations kept under these conditions for many generations showed a reduction of genetic variability in agreement with this value.

5. To investigate the possibility that the deleterious genes produced by irradiation would interfere with the response to artificial selection, a standard outbred population was irradiated and selected. In spite of the observed high frequency of recessive lethals produced, the response to selection was very similar to that of the standard population.

A mechanism for gene conversion is proposed which overcomes many of the difficulties that any copy choice model encounters. It is suggested that along with general genetic pairing of homologous genomes at meiosis, effective pairing over short regions of the genetic material occurs at the molecular level by the separation of the strands of the DNA double helices, followed by the annealing of strands from two homologous chromatids. If the annealed region happens to span a heterozygous site, mispairing of bases will occur. Such a situation may be analogous to that in DNA which is damaged by mutagens; the same or similar repair mechanisms may operate, and these, by adjusting the base sequences in order to restore normal base pairing, would bring about gene conversion in the absence of any genetic replication. The model indicates how precise breakage and rejoining of chromatids could occur in the vicinity of the conversion, so that conversion would frequently be accompanied by the recombination of outside markers. The model also proposes that the distance between two mutant sites on a fine structure map depends not so much on the frequency of a recombinational event occurring between them, but rather on the degree of inhibition of the processes of genetic pairing by the mutants themselves.

The model will explain almost all the data in a formal way, and it has the advantage over copy choice mechanisms for gene conversion in (1) being compatible with semi-conservative replication of DNA, (2) not invoking DNA synthesis during or after genetic pairing, (3) providing a molecular mechanism for close specific pairing, (4) making it unnecessary to postulate sister strand exchange or a process akin to this, (5) suggesting why rates of gene conversion in opposite directions are sometimes unequal and (6) providing an explanation of the clustering of mutant sites, a basis for map expansion and for the apparently capricious departure of fine structure maps from additivity. Although the model proposed is a general rather than a specific one, it suggests that the process of conversion and intragenic recombination is more complex than is usually believed, since it depends on several interacting factors. Nevertheless, it is hoped that the introduction of a model with this complexity will help to stimulate specific experiments, and that these will provide definitive information which would never be obtained if simpler models of conversion and intragenic recombination were believed to explain the genetic data sufficiently well.

1. It has been shown that metagons, gene-controlled units necessary for maintenance of mu particles in Paramecium aurelia, can be extracted from cells containing one or both of the dominant genes M1 and M2, and reinfected into other paramecia. Provided the latter contain mu particles before infection, the introduced metagons resume their normal function of maintaining the mu particles.

2. Homogenates containing metagons have been fractionated in various ways. The metagon activity is found in the sediment after centrifuging at 105,000 g. for 90 min., and is retained after deoxycholate treatment removing the microsomal membranes, and after phenol extraction removing the ribosomal protein. By lowering the magnesium concentration, some metagon activity passes from the microsomes into the supernatant.

3. Metagon activity in RNA fractions is destroyed by ribonuclease at a concentration of 5 μg. per ml.

4. The metagons both in extracts and inside the cells appear often to be aggregated in clumps, the individual units of which are each functionally active in maintaining mu particles in living cells.

5. It is concluded that the metagon may be considered as a very stable and repeatedly functioning form of ‘messenger’ RNA.

1. Inheritance of flower colour in Delphinium ajacis is controlled by a locus with three stable alleles: pb (blue) is dominant to pl (lavender), which is dominant to p (pink). An unstable allele, p*, exists in a number of states, distinguished by the pattern of their mutation to pb and p during the development of the sepals.

2. The rate of occurrence of blue sectors and spots in the developing sepals of p*p* plants is twice that in the sepals of p*pl plants. The rate of mutation to pb apparently falls during the development of the sepals and this is probably due to p* mutating also to the stable p allele.

3. The frequency of pb and p gametes from p*p* plants is twice that from p*pl plants.

4. The pb mutants from p* show no evidence of instability; the controlling element has transposed from the locus.

5. Some p mutants from p* are apparently stable; others can reacquire instability, especially during sexual reproduction. The latter are tentatively interpreted as due to transpositions of the controlling element to other sites within the gene.

6. The instability of p* is only shown in the presence of a dominant activator.

7. Evidence is presented of transposition of the controlling element from p* to a locus controlling the colour of the foliage.

Genetic recombination through the parasexual cycle, or some very similar system, was demonstrated. Diploid strains were very unstable, yielding about 95% haploid conidia from three-week-old cultures This high frequency of haploid segregants was at least partly attributable to greater sporulation of haploid mycelium, but may also reflect a higher frequency of haploidization than that found in Aspergillus nidulans.

Mitotic crossing-over also occurred frequently, and gave segregants homozygous for some markers but heterozygous for others. It was also detectable by changes in the phase of linked markers occurring during vegetative growth. Some heterozygous segregants were either aneuploids, or were formed by double mitotic crossovers.

Haploid segregants, derived from nuclei which had previously undergone mitotic crossing-over, were often recovered. This coincidence of mitotic crossing-over and haploidization in one nuclear lineage, together with the probable occurrence of double mitotic crossovers, makes mitotic analysis less clear cut than in Aspergillus nidulans.

1. Similar changes in the body-size of Drosophila melanogaster have been achieved by different developmental pathways, especially either by altering the duration of the early exponential phase of larval growth or by influencing the growth rate in the phase which is independent of time.

2. Such changes have been effected by selecting in the same population for larger or smaller size or shorter development time on chemically defined media, deficient in alternative nutrients. Selection for larger size on media deficient in protein or choline does not involve correlated changes in the larval period, whereas selection on media deficient in RNA does. The evidence suggests that shortage of this nutrient may be uniquely favourable for promoting a correlated change between body-size and duration of the larval period.

3. Strains which differ in presence or absence of such correlation are characteristically different with respect to gene-environment interaction. In the former, the differences due to selection are generally more fully or completely expressed when the diet is changed whereas in the latter this is not so, and different, especially competitive condition, leads to a drastic reduction of the difference.

4. How far the expression of the differences due to selection are affected, when the diet is altered, is also influenced by how long selection has been carried out. In early generations, the difference is only or best expressed in the special conditions provided during selection, but later on the changes due to selection are either fully expressed or partly so, as noted above.

5. Many of the differences in gene-environment interaction between selected strains can be accounted for in terms of variation in the duration of the exponential phase. Thus two lines selected for small body-size on low RNA or low protein diets responded in different ways to the same nutritional change—one became relatively larger and took porportionately longer to develop, the other became relatively smaller and developed in a shorter time.

6. There is clear evidence from various tests in which the amino-acid composition of the diet has been altered, that the nutritional requirements in the two stages of growth are not identical and this is consistent with the evidence for considerable genetic independence as well.

7. It is proposed that the first stage of larval growth, which principally determines the duration of the larval period and may also influence body-size, is canalized. Genetic variation which can influence this stage is present in the population but contributes little to the phenotypic variation of adult size, except under special nutritional conditions as when ribonucleic acid is the sole limiting nutrient. But, at the same time, such canalization is dynamic in the sense that the absolute amount of growth which is completed in the first stage may vary with respect to diet and thereby lead to correlated variation in the duration of larval life and adult size. But individuals of an adapted population behave alike in this respect so that gene-environment interaction which leads to correlated variation in the two characters is of a very low order.

8. The canalized phase sets a limit to the potential growth in the later stage and thereby influences greatly the mean value about which such growth is equilibrated. This canalization plays a major role in the general stability of growth relations and body-size although this is normally concealed by the high level of phenotypic variation. This interpretation can account for a great variety of data and provides a rational guide to further analysis.

The results of the analysis of 393 mitotic recombinants within the paba1 region of Aspergillus nidulans can be summarized as follows:

1. Reciprocal, non-reciprocal and probably inexactly reciprocal exchanges occur in intra-cistron mitotic recombination.

2. Negative interference observed in intra-cistron mitotic recombination in the paba1 region of Aspergillus nidulans is more intense than that observed in meiotic recombination in the same cistron.

3. In intragenic mitotic recombination multiple exchanges can involve three or even four chromatids within one effective pairing segment.

Several stocks of Paramecium aurelia that had never expressed an E serotype were examined for E-reacting material. The regular presence of the cross-reacting antigen G in these stocks ruled out the use of hapten inhibition and other standard immunological techniques. Consequently, a genetic approach was attempted in which hybrids of the E-deficient strains and non-E stocks were bred, and antigen isolated and tested for the existence of molecules with a specificity differing from that of the E-containing parent.

Gel diffusion analysis suggested that E antigen from a hybrid indeed could differ from the ‘normal’ E. One of these hybrid clones which behaved as though its E antigen may have possessed a determinant contributed by the E-deficient strain was used as an immunizing antigen. The antibodies elicited possessed specificity unique for the hybrid. Thus the possession of E-like determinants by E-deficient stocks was confirmed.

Mi-spotted (misp) is a new mutation in the mouse at the microphthalmia (mi) locus. It has no obvious visible effect in either the heterozygote (misp/+) or homozygote (misp/misp) and was discovered by virtue of its interaction with white (miwh). Mice of genotype miwh/misp are pale yellow with white spots; yellow areas later become ‘sooty’ at the first moult.

Though mice of genotypes a/a; misp/+ and a/a; misp/misp cannot be visibly distinguished from those of a/a; +/+, the amount of tyrosine-2-C14 incorporated in melanin in skins of 5-day-old mice of these genotypes differed. Assays of tyrosine incorporation were extended to include other non-agouti genotypes differing only at the microphthalmia locus. The amount of tyrosine incorporated was greatest in +/+ followed in order by misp/+, misp/+, misp/misp, miwh/+, miwh/misp, and miwh/miwh.

Pigment granules were examined in club hairs of these same genotypes for different regions of the hair shaft. Hairs of misp/+, misp/misp, and mi/+ could not be distinguished from +/+ either in number, kind or arrangement of granules. Hairs of miwh/+ showed reduced cortical and medullary pigment, especially distally, which was even more pronounced in hairs of miwh/misp. Medullary granules of miwh/misp varied greatly in size with a few large yellow-brown granules.

The XXY male mouse, of otherwise normal chromosome complement, is characterized by small testes, few spermatogonia, and spermatocytes in which the first stage of meiosis up to the pachytene stage can occur, although with a very low frequency. Pachytene autosomes are morphologically similar to those of the oöcytes. The sex vesicle is smaller and more condensed than in the normal male.

A paramecium generally bears on its surface but one immobilization antigen from among the many it may have the potentiality for expressing. By assaying soluble extracts of whole cells, it had been demonstrated previously that animals of the E serotype may possess the cross-reacting G antigen. Now the existence of these secondary antigens—immobilization antigens undetected by in vivo tests—has been extended to include unrelated antigens, e.g. G antigen in animals of C serotype.

The amount of these cryptic immobilization antigens varies from stock to stock; also within a stock cultures harvested at different times may have quite different quantities.

The secondary and primary G antigens appear to be indistinguishable by the criteria of antigenic specificities, immunoelectrophoretic mobilities sedimentation rates and ammonium sulfate solubilities. As to their distribution within the cell, both secondary and primary antigens are located primarily on or within the cilia.

The chromosomes of the two parental forms and those of the hybrid do not show any detectable numerical or large structural differences. The pairing in the hybrid is frequently abnormal in that both free ends (highly charged with stainable substances) of many chromosomes show strong pairing, while midsegments repel each other. This partial failure of paring suggests that in the two parental forms gene mutations rather than chromosomal structural changes are responsible for incipient divergence.

It is suggested that the stainable substance of the chromosomes acts as a carrier mechanism ensuring orderly pairing, segregation and numerical constancy of bivalents in the hybrid where the partner chromosomes have become partly non-homologous.

The distinction between long and short chromosomes is typical for the avian karyotype, its evolutionary significance is discussed.

Weak but statistically significant sexual isolation has been demonstrated among Vetukhiv's six experimental populations of Drosophila pseudoobscura, all originally descended from founders taken from cultures of the same hybrids from four geographic localities. These six populations were maintained separately for almost 4½ years and then tested for the existence of sexual isolation. The sexual isolation has arisen in the absence of any selection for isolation, evidently as a by-product of genetic divergence.

The ovalbumin locus and locus II (Lush, 1961) were found to segregate in a closed flock of White Leghorns. Three of the nine expected genotypic classes were absent and from this it is concluded that the two loci are very tightly linked.

1. Hybrid (C3H♀ × 101♂) male mice were given two doses of 600 r. acute x-irradiation eight weeks apart and outcrossed at the end of their sterile period. Their fully fertile sons were outcrossed and daughters of these sons were backcrossed to them, in order to study the rates of induction in spermatogonia of dominant and recessive lethal and visible mutations, as well as dominant semi-sterility.

2. F1 litter-size decreased by 15·2% at birth and 15·8% at weaning age, as compared with controls. This decrease was very largely due to dominant lethality acting at about the time of embryonic implantation. There was also a highly significant increase in the incidence of heritable semi-sterility, the estimated rate of induction of reciprocal translocations being 3·3% per gamete.

3. The dominant lethality was shown to be partly a secondary consequence of induced translocation heterozygosis. The estimated overall rate of dominant lethal induction was 10·6% per gamete, with ‘primary’ dominant lethals induced at a rate of 4·0% per gamete.

4. The estimated mutation rate to dominant visible mutations was 4·6 × 10-7/gamete/r., but this was based on only two mutations in the irradiated series.

5. In the backcross generation there was again significantly more embryonic death in the irradiated series, mainly at the small mole stage and this was attributed to induced lethal mutation. The survival in the irradiated series was 96·80% of that in the controls and from this the rate of induction of recessive lethals was calculated to be 2·5 × 10-4/gamete/r. There was no evidence of the induction of lethals acting later than 14 days' gestation.

6. The estimated rate of induction of recessive visible mutations was 1·8 × 10-5/gamete/r., but the results showed heterogeneity, probably due to personal factors.

7. No significant sex-ratio differences were found.

8. The results were compared with those of specific locus and other relevant experiments. The rates of induction of recessive lethal mutations and of recessive visibles were both lower than might have been expected. On these results the mouse was only 4–5 times more sensitive than Drosophila to the mutagenic effects of radiation.

1. F1 (CSH♀ × 101♂) male mice were given 1200 r. 60Co Υ-irradiation over welve weeks and mated twelve weeks after the end of irradiation. The incidences of foetal and neonatal lethality and of semi-sterility in their offspring were compared with those in controls.

2. Embryonic survival to 15 days in the irradiated series was 98·2% that of controls, while the incidence of semi-sterility was 0·9% compared with nil in the controls. Neither of these differences is significant.

3. Comparison of these results with the significant rates of induction of dominant lethals and translocations in a previous experiment, in which a dose of 1200 r. acute x-irradiation was given to males of the same hybrid stock, show the existence of a dose-rate effect. Its magnitude cannot at present be accurately estimated.

4. The reasons for this effect are discussed. It is concluded that the main cause of the lowered translocation yield is that restitution of breaks will be favoured at low dose-rates, with less opportunity for the formation of interchanges. This could partly account for the lowered rate of induction of dominant lethals as well, but a full explanation is not yet possible.

The paper on the analysis of data from transduction experiments with Salmonella typhimurium, which was published in Genetical Research (Dawson, 1963), unfortunately contained an error on p. 419. In calculating the limiting values X/Y, the formulae for d and d′ are correctly stated, but their solutions are transposed. The last and third last lines on p. 419 should therefore be interchanged. In the arithmetic example on pp. 420 and 421, a similar interchange of the calculations of d and d′ is necessary. The maximum value of a/b is then:

and the calculation of the minimum value should be:

These values of 2·20 and 1·23 are to be compared with the values of 2·23 and 1·24 in the published paper.

1. A mild diabetes insipidus is associated with the oligosyndactyly caused by the dominant gene Os. No recombinants were observed between the diabetes and the oligosyndactyly so the diabetes is probably a pleiotropic effect of the Os gene.

2. There are one or more modifying genes which in combination with Os enhance the manifestation and cause a severe diabetes insipidus. This affects both sexes and becomes progressively worse in older animals, the average water intake reaching 50–60 ml. per 24 hours, or 1·7 times the body weight.

3. The modifying gene or genes, in the absence of the Os gene, themselves produce a mild diabetes insipidus, which becomes severe in some old females.

4. The severe diabetes insipidus associated with Os and the modifying genes together is probably renal in origin.