An extension of two-way selection (i.e. selection of mutant from wild-type and vice versa within the same locus and with the same efficiency) to four different mutational or segregational situations was made possible by using acetate, fluoro-acetate and other substances related to their metabolism.

Two types of mutants resistant to fluoro-acetate were selected, the first of which (designated fac) cannot grow on acetate as the sole carbon source, while the second (designated fan) can.

Commencing with either a fac or a fan strain a double fac fan strain may be isolated, which is much more resistant to fluoro-acetate than either single mutant strain. Such double mutant strains may also be obtained by crossing a fac to a fan strain. Various characteristics of growth response of these strains on various media were observed.

fac mutants are recessive and map in three meiotically unlinked loci, one in linkage group V and two in linkage group VIII.

fan mutants are recessive and map in five loci, one in each of the linkage groups V, VII and VIII, and two linked in linkage group VI.

Most fac mutants isolated did not revert and this failure is considered genuine. Of the revertants tested, most resulted from extra-cistron suppressors, while revertants of two fac mutants resulted from very closely linked or intra-cistron suppressors.

It is argued that the findings indicate the existence of two pathways for acetate utilization in Aspergillus nidulans, a major and a minor; fac mutants are blocked in the major pathway, fan mutants in the minor pathway.

1. Rates of gain and loss of acclimatization to temperature of males from two inbred lines and the hybrids between them were measured by recording their survival times in dry air at a lethal temperature (34°C).

2. All hybrid males lost acclimatization to temperature more quickly than did inbred males. B/K males gained acclimatization to temperature more quickly than any other group, but the K inbred males gained acclimatization more quickly than did either the K/B males or the B males. In all cases acclimatization is gained more quickly than it is lost.

3. The extent of acclimatization to temperature, as measured by the difference in survival times of 15°C. and 25°C. acclimatized flies in a range of lethal temperatures, was not found to be different in inbreds and hybrids.

4. The results suggest that hybrids can produce the enzymes necessary for acclimatization to temperature more rapidly than inbreds and confirms the hypothesis that hybrids are biochemically more versatile than inbreds.

5. The difference between the rates of gain and loss of acclimatization to temperature suggests that the processes involved in the enzyme changes are temperature dependent.

6. The absence of a difference in the extent of acclimatization to temperature indicates that both inbred and hybrid D. subobscura are capable of producing those enzymes necessary for temperature acclimatization.

7. The high values of the temperature coefficients for heat death indicate that this process involves protein (enzyme) denaturation.

8. An ageing effect was observed in inbred flies.

Addition to the food of Drosophila larvae of DNA from calf thymus induces a considerable number of recessive lethal mutations in the 2nd chromosome. An analysis of sixty-six such lethals showed that most of them affect the same segment containing probably some thirty to thirty-five sub-units capable of mutating together or separately.

1. A histochemical method has been applied to the detection of alkaline and acid phosphatase mutants in single colonies of Aspergillus nidulans.

2. With the above method it has been possible to isolate mutants in which the alkaline and acid phosphatase activities are affected either separately or simultaneously.

3. Crude extracts of wild-type A. nidulans contain four electrophoretically distinct phosphatase components, two with activity at alkaline pH and two with activity at acid pH. Genes affecting three of the four components have been identified.

4. Two suppressor mutants of an alkaline phosphataseless mutant (palB7) have been isolated. In a strain carrying palB7 and one of these suppressors, the restoration of an alkaline phosphatase component is accompanied by loss of the faster acid phosphatase component. In a similar strain carrying the other suppressor, the partial restoration of the alkaline phosphatase component goes with an electrophoretic alteration of the slower acid phosphatase component.

5. Genetic analysis of twenty-seven mutants has resulted in the identification of fifteen loci affecting the phosphatases. All these loci have been assigned to linkage groups, and twelve of them were also mapped meiotically in relation to other loci.

6. One possible model (based on heteropolymeric proteins) has been proposed to account for the electrophoretic and genetic data on the various phosphatase and suppressor mutations.

(1) F1-hybrid mice derived from a cross of the highly inbred strains: C57BL/6 and BALB/c, were tested for inherited changes of histocompatibility by an orthotopic inter-exchange of tail-skin grafts. The fathers of tested mice received either 522 rads of gonadal X-irradiation, or received no irradiation 2 months prior to mating.

(2) Thirty-two mice with altered histocompatibilities were found in a total of 2572 complete tests. All of those mutant mice (twenty-one) that produced an adequate number of offspring were shown to pass the incompatibility on to their progeny.

(3) Mutants were classified as to whether they effected a gain, a loss or both a gain and a loss in antigen specificity as determined by whether they rejected skin of donor mice or their skin was rejected by host mice. Twenty-six were clearly of the gain type, five were most likely gain type and only one showed both a loss and a gain effect. There was no clearcut evidence that loss types had occurred. The preponderance of gain types was tentatively explained as an artifact of the system used for the assay.

(4) Several of the detected mutants were probably from parents carrying mutations that originated in past generations, for some mutant mice occurred in clusters.

(5) There was no apparent effect of paternal irradiation (522 rads) on mutation frequency. The induced mutation rate was estimated to be less than 2·6 × 10−5/ gamete/rad.

(6) Independent data on isografts from F1 hybrids of proven non-carrier pedigreed parents provided an estimate of spontaneous mutation rate of 6·75 × 10−3/ gamete.

(7) The estimate of doubling dose (greater than 260 rads) was consistent with the estimates for recessive lethals and visibles in mice.

Calf-thymus DNA was mixed with the larval food of Drosophila melanogaster and complete and mosaic lethals were scored in both the X- and 2nd chromosomes. There was a decided mutagenic effect on the 2nd chromosome in both sexes. No complete sex-linked lethals were produced in males, but the production of a moderate number of complete lethals in females and of mosaic lethals in both sexes suggests that, in the absence of germinal selection, the X-chromosome is not completely refractory to the treatment.

The extension of the 2nd chromosome test to later generations showed that mosaics often gave rise to further mosaic progeny. Tests for allelism showed that lethals in the same mosaic line formed series of overlapping deficiencies, indicating that the primary effect in these cases was a transmitted instability of a narrow chromosomal region. Cases in which several mosaics arose out of one mosaic parent show that this instability must have replicated as instability.

An experimental evaluation of the effect of mating systems and selection upon an additive trait thought to be highly heritable was made. There were two similar replications. Each consisted of a mass selected and randomly selected group, with five mating systems within each group.

Realized heritabilities in the mass selected lines were considerably less than was expected prior to the initiation of the experiment, and averaged approximately fourteen percentage points less than heritability estimated from the zero generation. This in turn resulted in smaller correlations between the genotypes of mates than had been previously expected in the assortatively and disassortatively mated lines.

The average response of the mass selected, assortatively mated lines was slightly more than the mass selected, randomly mated lines, though not statistically significant. This result seems to conform to theoretical expectations.

In the mass selected lines, estimates of phenotypic and genetic variance declined regardless of mating systems. There was a tendency for phenotypic variances to decrease in the randomly selected lines, but this was not the case for estimates of genetic variance.

As an aid to selection, it seems that assortative mating would be of little value with traits of low or intermediate heritability but might be useful if the trait is highly heritable.

According to the polaron hybrid DNA model, the initial nucleotide-chain breakage leading to genetic recombination takes place only at the linkage points which define the ends of each polaron. The term dissociation cycle is proposed for the postulated series of events from primary breakage at a linkage point to the final breakdown of unpaired chains. At mutant sites, the mispairing in hybrid DNA may persist and give rise to post-meiotic segregation, or a correction process may operate by which molecular homozygosity is restored. This causes conversion, which may be evident as reciprocal or as non-reciprocal recombination.

The implications of this model are that a crossover occupies a segment of the chromosome, and that conversion is a process which takes place when a mutant site happens to lie within such a segment. Although crossovers appear to be initiated at fixed points outside or at the ends of the genes, they extend into the gene on one side or the other. The negative interference between recombination events over short intervals of the linkage map is attributed to the association between crossing-over and the conversion which is likely to occur at any mutant sites which happen to lie within the crossover. In the same way, non-crossover hybrid DNA can also lead to conversion, and hence to negative interference.

The relevant data on genetic recombination have been found to fit this model, and have led to the following main conclusions:

(1) The polaron may coincide with the cistron, or in some instances may possibly include more than one cistron. As a corollary to this, there appear to be two kinds of cistrons: unipolar, where all the recombination is initiated from the same end, and bipolar, where it is sometimes initiated from one end and sometimes from the other.

(2) In bipolar cistrons there is usually a preponderance of recombination initiated from one end over that from the other. In five genes where the orientation with respect to the centromere is known, two show a preponderance in favour of the proximal end and the other three in favour of the distal end. It seems possible that this asymmetry within the gene may reflect intrinsic differences in the frequencies with which the dissociation of the DNA molecules is initiated at different linkage points.

(3) The hypothesis of a fairly constant amount of newly-synthesized DNA per dissociation cycle, irrespective of how it is distributed along the four templates from a linkage point, leads to a number of predictions for which there is evidence in support. These concern the detailed pattern of crossover and non-crossover hybrid DNA within the gene.

(4) Specific differences in intragenic recombination are attributed to differences in the pattern of DNA synthesis. The predominantly non-reciprocal recombination found within cistrons of Neurospora crassa would be explained if synthesis extends unequally from the linkage point in the two chromatids. The higher frequency of reciprocal recombination found in Aspergillus nidulans is attributed to more equal extension.

(5) Differences between meiotic and mitotic intragenic recombination both in A. nidulans and in Saccharomyces cerevisiae are explained on the supposition that more DNA synthesis per dissociation cycle occurs at mitosis than at meiosis.

(6) Clustering of sites in maps of alleles based on recombination frequencies is attributed to a rather limited range of variation in the lengths of the newly synthesized nucleotide chains.

1. Hairless (H), a dominant mutant of Drosophila melanogaster, affects the chaetae.

2. Various ‘intensities’ of effect are interpreted as representing different times in chaetal development at which deficiency of ‘+H substance’ is encountered. ‘Temperature effective period’ studies confirm this view.

3. The chaetae at different sites are liable to characteristically different ‘intensities’ of effect. In other words a particular site tends to be affected at a limited time in its development. If it is supposed that a single period of deficiency of +H substance accounts for effects on all chaetae, then it follows that development of the various chaetae is asynchronous. Some histological observations tend to support this prediction.

The implications of asynchrony with respect to pattern formation are discussed.

4. It is argued that the source of +H substance may be an endocrine organ, the ring-gland.

5. Two modifiers Su-H and E-H, whose expression and linkage relations are described in detail for the first time, are, it is suggested, respectively ‘constitutive’ and ‘super-repressed’ mutations of a ‘regulator’ locus controlling negative feed-back on the +H locus.

Diploid strains of Coprinus lagopus have been synthesized from common A heterokaryons either as oidial colonies or sectors. The criteria of growth rate and colony morphology on selective medium were used to distinguish between diploid and heterokaryon colonies. The average oidial size and hyphal width of diploid strains was significantly greater than that of the haploid parental strains.

Diploid monokaryons were very stable and only rarely produced haploid segregants. However, aneuploid intermediates in haploidization have been identified and these segregated further to give haploid monokaryons with recombinant genomes.

Dikaryons formed from diploid and haploid strains produced fruiting bodies. Meiosis and basidiospore production were irregular owing to the formation of triploid or partially triploid fusion nuclei in the basidia. In contrast to their stability in monokaryons, diploid nuclei tended to be unstable when combined in a dikaryon with a haploid nucleus, and often underwent partial haploidization before fruiting. Segregation of genes in the basidiospore progeny reflected whether haploidization had occurred before or after the formation of the fruiting body. If the haploid nucleus had a B mating-type allele common to the diploid nucleus, haploidization effected loss of the common allele.

Four ‘master’ strains of Aspergillus nidulans, three of which are marked on each of the eight chromosomes, are used for assigning genes of unknown location to linkage groups. In this technique a heterozygous diploid is synthesized between one ‘master’ strain and a strain carrying an unlocated marker. This diploid is haploidized by growth on p-fluorophenylalanine, and the haploids thus obtained are classified for recombination between the unlocated marker and each of the markers of the ‘master’ strains. The marker or markers of the ‘master’ strain which show no recombination with the unlocated marker identify the chromosome pair on which the latter is located. One example is presented for each of the four ‘master’ strains.

By comparing genetic correlations between an X-rayed and a control population of rice, parameters for the strength of pleiotropic effects of quantitative genes have been estimated. It is evident that the gene-set which is responsible for main rachis formation and is therefore of primary importance for panicle formation, is pleiotropically controlling the development of rachillas and basal internode. It is found that the pleiotropic control over the development of higher rachillas is very powerful but less strong over the lower ones and basal internode.

Developmental relationships among these characters have also been investigated by measuring the genetic correlations between their developmental instabilities. The basis of our inference is the hypothesis that if two characters which are found to be pleiotropically controlled by the same set of genes take their own developmental paths from a very early stage, they will show only slight correlation between their developmental instabilities. If, on the contrary, they are taking the same developmental path and their differentiation sets in late, the correlation coefficient will be high.

The serum transferrin and post-albumin phenotype distributions of 228 Sahiwal, 138 Nganda, 265 Boran, 114 Tanganyika Shorthorned Zebu, 72 Teso and 267 Ankole cattle from East Africa were determined.

Five transferrin alleles, TfA, TfB, TfD, TfE, and TfF were present in all the breeds examined, and a sixth allele, TfG, was present in three of the Borans. TfE and TfF were the most frequent alleles, except in the Nganda cattle where TfA was the most frequent. TfB had a frequency of less than 0·1 in each breed. Two post-albumin alleles, PaF and Pas, were present in each breed. In each breed except Sahiwal PaF was two to three times more frequent than Pas. In the Sahiwal PaF and Pas had about the same frequency. It was concluded that both transferrin and post-albumin gene frequencies in East African cattle differ significantly from the corresponding frequencies in European cattle.

There was no evidence of an excess of heterozygotes in the post-albumin system other than that expected from the use of relatively small numbers of bulls in these herds. However, allowing for the same factor in the transferrin system, there appeared to be an excess of transferrin heterozygotes in the cattle populations sampled although the extent of this excess could not be calculated accurately.

A method is now available for synchronizing the division of populations of cells of the smut fungus Ustilago maydis. In two experiments carried out with a diploid strain heterozygous for several biochemical markers, samples of cells were removed at intervals through the synchronized division cycle and treated with a constant dose of ultra-violet light. Cell survival and the frequency of the various recombinants resulting from induced mitotic crossing-over were recorded. In addition the period of DNA synthesis in the unirradiated population has been measured. During this period the cells are very sensitive to ultra-violet light and those that survive contain the highest proportion of induced recombinants. In so far as the markers make it possible to locate the position of cross-overs, cells which are irradiated early in the period of genetic replication show most crossing-over towards the ends of the chromosome arms, whilst cells which are treated late in this period show crossing-over near the centromeres. The data are most easily interpreted by supposing that chromosome replication begins at the ends of the arms and proceeds to the centromere, and that the temporary interruption of this process by ultra-violet light can result in pairing and crossing-over in the vicinity of the points of interruption.

The present series of papers is concerned with the variation shown by date of ear emergence, seed weight, and measures of seedling growth rate in the Australian Commercial population of Phalaris tuberosa L. In this first communication, the statistical theory necessary for the interpretation of the available experimental observations is developed. The treatment involves a consideration of the effects of partial self-fertilization under open-pollination, of phenotypic assortative mating, and of maternal effects, on the expectations of the observed covariances among relatives.

Six new am mutants of Neurospora, am14–am19, with defective formation of NADP-linked glutamate dehydrogenase, were isolated following treatment of conidia with nitrous acid. This brings the number of genetically distinct and viable am mutants to sixteen. Heterocaryon-compatible isolates of each of the new mutants were tested for complementation with each of the mutants previously known. A number of new complementary combinations were found which add to the complexity of the complementation map which, however, remains linear.

The mutants which show complementation are am1, am2, am3, am7, am14 and am19. It has proved possible to isolate an altered form of glutamate dehydrogenase from each of these except am14, which appears to produce no protein fractionating like the normal enzyme. Among the non-complementing mutants, am4 produces an easily-isolated inactive form of glutamate dehydrogenase. These results agree with the immunochemical findings of Roberts & Pateman (1964).

Of the mutationally altered forms of the enzyme, the am1, am2, am3 and am7varieties are electrophoretically identical or closely similar to the normal protein, while the am4 and am19 varieties move faster towards the anode at pH 8·5, am19being the faster of the two. The am19 protein, like the am2 and am3 proteins previously reported on, can be activated to give some enzyme activity, but the activity obtained is much lower for this mutant than for am2 or am3.

All the complementary pairs of mutants, including those involving am19, form active enzyme varieties which have very close to normal electrophoretic properties. In several cases the complementation enzyme is less stable to heat than the wild-type enzyme.

The variation shown by the Australian Commercial population of P. tuberosa in respect of date of ear emergence, seed weight and seedling weight has been analysed, and the interrelationships among the variables characterized. All three characters show appreciable additive genetic variation, in the sense that approximately seven generations of artificial selection would be sufficient to push the population mean for each trait beyond the range shown by introduced ecotypes.

Apart from the positive association between seed weight and seedling weight due to maternal influence, the three variables are to a large extent genetically independent in this locally adapted interbreeding population. It is therefore probable that the negative ecotypic correlations between seedling growth rate and date of ear emergence, and between seed weight and date of ear emergence, would rapidly be dispelled under random mating in a synthetic population.

Under open-pollination, date of ear emergence has been shown to be subject to phenotypic assortative mating of degree ρ = 0·78, approximately 53% of the variation being additive genetic. Variation in seed weight within the strain is extensive, with a heritability of 0·79. Neither character shows evidence of important genotype × years interaction.

Variation in seedling weight involves an appreciable genotype × environment interaction component, and has a heritability of only 0·17 which includes variation due to genetically determined maternal effects. The correlation between the seed weight of an ovule parent and the ‘ true’ mean seedling weight of the derived maternal half-sib group is of the order of 0·57. It has been estimated that the correlated response per generation in seedling weight, due to selection for seed weight, is 0·54 times that expected from direct selection.

Mutant genes in linkage groups I (mating-type chromosome), VI and VII have been transferred from Neurospora crassa to N. sitophila by hybridization and repeated backcrossing. Recombination between these genes has been studied from five-point crosses involving linkage group I and three-point crosses involving linkage groups VI and VII of the two species.

The results show significant differences in the amount of recombination between some of the genes in the proximal regions of the mating-type chromosomes of the two species. They indicate proximal localization of crossovers in the mating-type chromosome of N. sitophila. The results also show significant differences in recombination frequency between the genes in linkage group VI and a close similarity in linkage group VII. They further show that the centromere in the two species may not be interfering with crossing-over in its vicinity to such an extent as to be of any evolutionary significance.

Tetrad data from five-point crosses involving linkage group I (mating-type chromosome) and three-point crosses involving linkage groups VI and VII of Neurospora crassa and N. sitophila have been analysed in order to detect the phenomena of chromatid and chiasma interference on a comparative basis. Marker genes were transferred from N. crassa to N. sitophila by hybridization and repeated back crossing. The details of the methods of transfer and of making crosses have been described in a previous paper (Scott-Emuakpor, 1965).

The level of liver catalase activity in substrain C57BL/6 mice is only approximately half that in substrain C57BL/He. That this difference was due to a single major gene with low level of activity dominant to high was indicated by analysis of the F1, F2, and backcross hybrids and confirmed by progeny tests of first back-cross male segregants. The gene symbol Ce is suggested.

The absence of any difference between reciprocal hybrids indicated no extra-chromosomal maternal influence.

There was no evidence that this gene controlling liver catalase had any influence on the level of kidney catalase activity for this did not vary between the two parent substrains or the hybrid groups.

Males consistently had higher liver and kidney catalase activity than females. The difference was more pronounced in respect to kidney catalase, males having about twice the activity found in females.