It is shown that the distribution of the sum of heterozygotes, due to mutant gene(s), that appear in a finite population is invariant under geographical structure, provided that the mutant gene has additive effect on fitness and migration does not change the genetic constitution as a whole population. The expected number of heterozygotes is 2N when Ns = 0 and gradually rises to 4N as Ns increases provided s remains small, where N = the total population size and s = selective advantage of a mutant gene. The distribution of the heterozygosity summed over those generations in which the gene frequency in the entire population is specified, is also shown to be invariant. In the case of a neutral mutant, the density is equal to 4(1 − Y) where Y is the frequency of the mutant in the whole population, and in the selectively advantageous case, it is approximately equal to a constant function 4, provided that the population size times selection coefficient is sufficiently large. These quantities conditional on the fixation of the mutant are shown to be invariant and some special cases are obtained explicitly.

It was demonstrated that the number of generations until fixation or loss of an overdominant alleles is influenced by random fluctuation of selection coefficients. When 2 < Vs, where is the mean selection coefficient against either homozygote and Vs is the between -generation variance of the selection coefficient, overdominance generally accelerates rather than retards fixation of segregating alleles. This finding should have important bearing on our consideration of the behaviour of polymorphic variants which are nearly neutral but have very slight overdominance. When the population size (Ne) is extremely large, not only Ne but also /Vs have to be considered in discussing the effectiveness of overdominance.

Data are presented from a balanced backcross experiment involving three linkage group VI markers in the house mouse. These establish the order N–Ca–bt (naked–caracul–belted), and confirm the unusual recombination values reported earlier; the values for male heterozygotes are about 4 times those for the female ones. The linkage group is extended by the linkage of miniature, mn, with N and Ca, here reported. Data are given which establish the order mn–N–Ca–bt; they indicate that the recombination values for males may be greater than those for females for some way to the left of the N–Ca–bt segment.

The Neurospora crassa photoreactivating enzyme has been assayed for by the Hemophilus influenzae and Bacillus subtilis transformation systems. In contrast to the H. influenzae system, u.v.-treated transforming DNA from B. subtilis did not give evidence of reactivation of u.v. lesions by crude enzyme extracts from N. crassa when exposed to photoreactivating light. The u.v. dose required to inactivate B. subtilis transforming DNA is about ten times that required to inactivate H. influenzae DNA to the same level of survival. This difference in dose required to inactivate DNA's of about the same base composition probably reflects the greater u.v. resistance of the B. subtilis recipient strains used. Hypotheses are considered which suggest that N. crassa crude enzyme extracts contain either nucleases which degrade B. subtilis transforming DNA excessively or an inhibitory factor which affects the transformation process itself.

The inheritance of self-incompatibility proteins was studied in three homozygous self-incompatible genotypes of Brassica oleracea var. capitata and their F1 and F2 progenies. The presence or absence in the stigma of incompatibility proteins was determined by immunodiffusion and independently by disk electrophoresis. Certain proteins (antigens) were present in F1 and F2 plants in exact correlation with segregation of the S alleles as determined by phenotypic expression of incompatibility. An S allele–protein–phenotype relationship was thus verified.

A cross of a leopard frog heterozygous for the dominant Burnsi gene (B/ +) with a wild-type (+ / +) resulted in a large excess of B/ + progeny. Two descendent lines established by these B/ + progeny are characterized by excess +/ + progeny. These seemingly contradictory data are reconciled by postulating the existence of a dominant subvital gene (Sbv) linked to the + allele of Burnsi in the initial cross. Progeny used to establish subsequent lines were recombinants with Sbv linked to B. This proposed linkage would constitute the first case of linkage between two mutant loci in anuran amphibians.

We have studied genetic variation at 27 loci in 42 samples from natural populations of a neotropical species, Drosophila equinoxialis, using standard techniques of starch-gel electrophoresis to detect allelic variation in genes coding for enzymes. There is considerarle genetic variability in D. equinoxialis. We have found allelic variation in each of the 27 loci, although not in every population. On the average, 71% of the loci are polymorphic – that is, the most common allele has a frequency no greater than 0·95 – in a given population. An individual is heterozygous on the average at 21·8% of its loci.

The amount of genetic variation fluctuates widely from locus to locus. At the Mdh-2 locus arout 1% of the individuals are heterozygotes; at the other extreme more than 56% of the individuals are heterozygous at the Est-3. At any given locus the configuration of allelic frequencies is strikingly similar from locality to locality. At each and every locus the same allele is generally the most common throughout the distribution of the species. Yet differences in gene frequencies occur between localities. The pattern of genetic variation is incompatible with the hypothesis that the variation is adaptively neutral. Genetic variation in D. equinoxialis is maintained by balancing natural selection.

The amount and pattern of genetic variation is similar in D. equinoxialis and its sibling species, D. willistoni. Yet the two species are genetically very different. Different sets of alleles occur at nearly 40% of the loci.

Among temperature-sensitive mutants of Escherichia coli a strain was discovered requiring D-alanine for growth. It was proved to possess an altered alanine racemase. The structural gene for this enzyme, designated alr, is located between metB and pur A. The properties of the enzyme and its locus suggest that it is not under control of the mechanisms which regulate mucopeptide formation. A suppressor of the alr mutation was discovered near trp, and termed msuA.

Populations of the slug Arion ater rufus sampled from several localities in England and the Netherlands are polymorphic for different electro-phoretic variants of digestive-gland esterase and salivary-gland tetra-zolium oxidase. Samples of Arion ater ater, which is endemic to the British Isles, were found to be monomorphic for these enzymes. Localized populations of A. a. rufus in Britain could have originated from specimens imported accidentally from continental Europe. There is evidence for gene flow between overlapping populations of the two subspecies. In one of the English populations of A. a. rufus, studied in detail, polymorphism for esterase and tetrazolium oxidase is shown to be balanced. Heterosis may be an important factor contributing to the maintenance of balanced polymorphism for tetrazolium oxidase in this population.

Extrachromosomal streptomycin and tetracycline resistance in Staphylococcus aureus E169 has been transduced to three different recipients. An analysis of the transductants demonstrates that: (1) in most cases the behaviour of the markers in the transductants is similar to that in the donor; (2) the markers are co-transduced at frequencies of 2–44% and the frequency is highest when the selected marker is streptomycin resistance; (3) in the co-transductants the markers segregate independently, suggesting that they are unlinked.

A wild strain of Klebsiella aerogenes (V9A), which contains a plasmid Fklac carrying the genes of the lac operon, gives two mutant cell types, recognized by the appearance of their colonies on MacConkey lactose agar. These are referred to as ML− and ML−/+, wild-type being ML+. ML− cells can grow rapidly on 1% lactose as carbon source but very slowly on 0·2% unless induced by TMG or D-fucose, or by previous growth on galactose, melibiose or raffinose, which enables them to grow rapidly on 0·2% lactose for 2–4 cell generations. Previous growth on 1% lactose does not induce the ability to grow rapidly on 0·2% lactose. It is concluded that ML− cells have a defect in the lactose permease gene which allows slow uptake of lactose when the external concentration is 0·2% and more rapid uptake when the external concentration is increased. In addition, TMG, D-fucose, galactose, melibiose and raffinose induce one or more other galactoside permeases which can accumulate lactose efficiently but are not induced by lactose. ML−/+ cells can grow normally on 0·2% lactose as carbon source, but only after a substantial lag when transferred from glucose, glycerol or sucrose, and after an even longer lag when transferred from melibiose or raffinose. Wild-type cells (ML+) grow normally on 0·2% lactose after a short lag of less than a cell generation time, when transferred from any other carbon source. Cells of each of the three phenotypes (+, −/+ and −) can mutate to give both of the other two phenotypes. Incomplete genetic evidence suggests that the ML− mutation is a result of a reversible change in the Fklac plasmid.

The relationship between the transfer systems of several plasmids was investigated, using as criteria complementation of a series of transfer-deficient Flac mutants, the efficiency of plating of F-specific phages, and identification of surface exclusion systems. The transfer systems of ColV2 and ColVBtrp were similar to that of F except for surface exclusion: ColVBtrp specified a surface exclusion system different from that of F, and ColV2 did not specify any detectable system. The transfer system of R1–19 was also similar to that of Flac, but the products of traA, traI and traJ were plasmid-specific. R1–19 determined the same surface exclusion system as ColVBtrp, and this was under the control of the transfer inhibitor. The transfer systems of ColIbdrd and Flac were unrelated. ColEl was transferred by Flac traI− mutants, but not by mutants in other cistrons.

The activity of several enzymes has been determined in the livers of homozygous obese and adipose mice, their normal litter-mates, and phenocopies induced in normal mice by aurothioglucose (ATG) injections.

Obese, adipose and ATG mice had higher activities of ATP citrate lyase, malic enzyme (NADP malate dehydrogenase) and pyruvate kinase than normal mice. Heterozygote activities are indistinguishable from wild-type. There was no difference between normal and fat litter-mates in the activity of malate dehydrogenase (NAD-linked), lactate dehydrogenase, isocitrate dehydrogenase and fumarase.

Crosses between mice doubly heterozygous for roth the ad and ob genes produced offspring that were only ‘fat’ or ‘normal’ and no offspring could be phenotypically recognized as the double mutant, either physically or in terms of ATP citrate lyase activity.

Gas–liquid chromatography of the fatty acids of the depot fat showed no differences between any of the types of litter-mate.

The alterations found in enzyme activity in obese and adipose mice are compared to several other enzyme activity differences reported in the literature for obese mice. These are discussed in relation to genetical criteria that may be estarlished to assess, from quantitative data, whether an enzyme is the site of the primary lesion in a mutant pheno-type. Some general observations are made on genetics and the control of metabolism.

The sex-linked gene, brindled, in the mouse produces a coat-colour variegation in heterozygous females. There is much individual variation in the relative areas of mutant and wild-type colour, but it was not known if any of this variation was genetic. The main object, when the experiments were started, was to test the simple expectation of the Lyon hypothesis, that if X-inactivation is random the variegation should not be modifiable by selection. On the assumption that the variegation is due to X-chromosome inactivation, modification by selection would show that the inactivation process, or some property of the derived cell populations, is under genetic control. Heterozygous females were accordingly selected for the area of coat showing the mutant colour. Selection based on individual phenotypes was ineffective, but four cycles of reciprocal recurrent selection based on progeny-means produced a ‘High’ line with 64% mutant area and a ‘Low’ line with 30% mutant area, from a base population with 53% mutant area. Autosomal modifiers were not responsible for the response; the difference between the selected lines was entirely due to properties of the X chromosomes carrying the brindled gene. The changed properties of the X chromosomes were not restricted to the locus of brindled, but extended at least as far as the locus of tabby. The chromosomes carrying the wild-type allele of brindled were not altered by the selection, but normal X chromosomes from other strains affected the degree of variegation. It was concluded that the difference between the selected lines was due either to non-random inactivation or to somatic cell selection. It was not possible to distinguish between these two mechanisms. The results obtained in these experiments with a structurally normal X chromosome were in all essentials similar to those obtained by Cattanach with his X-autosome translocation.

Measurements of chiasma frequency over a range of temperatures from 9 to 35 °C in euploid wheat and lines nullisomic for chromosome 5D showed the absence of chromosome 5D greatly to increase the sensitivity of chiasma frequency to temperature, resulting in complete univalence at the lowest temperatures. Careful examination of meiotic prophase showed the lowering of chiasma frequency to be correlated with failure of zygotene chromosome pairing, justifying the use of the term asynaptic. Observation of the pairing behaviour of an isochromosome in the nullisomic 5D background suggested that the asynapsis was due to a failure in the mechanism of chromosome pairing rather than of the pre-alignment of homologues. The observed effects in the absence of chromosome 5D could be due to the presence of a recessive allele at the locus of chromosome 5A, also known to control stability of chiasma frequency to temperature. In conclusion it is pointed out that in euploid wheat the sensitivity of chiasma frequency to temperatures within the normal meteorological range could influence the cytological stability of the wheat crop.

Several temperature-sensitive mutants of Escherichia coli were isolated which lyse at the restrictive temperature. Some of these possess a biochemically defined lesion in cell-wall mucopeptide synthesis. Three genes, termed murC, E and F, have been localized between the azi and leu markers. From transductional data a fine structure map was constructed of the mur mutations, establishing the order of the genes. The genetic relationship between these cell wall genes and neighbouring genes involved in cell division is discussed.

A genotype of wheat deficient for a pair of chromosomes stabilizing chiasma frequency against extremes of temperature was investigated to determine the position and duration of temperature sensitivity with respect to first metaphase of meiosis. Temperature changes over a critical range, followed by sequential sampling and measurement of chiasma frequency, showed a relatively short temperature-sensitive stage, the position and duration of which were dependent on the final temperature used. Comparison with meiotic timings made independently showed that the temperature-sensitive stage occurred in the premeiotic interphase. Euploid wheat was shown to have a stage in chiasma formation sensitive to high-temperature treatments at a similar time.

Comparison with the work of others showed that the sensitive stage lay between the last premeiotic mitosis and the start of DNA synthesis. This modification of chromosome pairing at a much earlier stage than has been previously demonstrated is further evidence that the processes of chromosome pairing and crossing-over are probably more complex than formerly envisaged.

A strain of Drosophila, homozygous for the variably penetrant gene tu bw, which causes the formation of abnormal masses of melanizing haemocytes (melanotic tumours), has been reared on defined axenic diets containing various sterols, both singly and in pairs. Both optimal and deficient nutritional levels of sterol have been employed, as well as certain sterols inadequate by themselves to support development. The effect of these diets upon probability of tumour formation has been studied in relation to their nutritional adequacy, as defined by the growth-rate, survival, and in one case, adult body-weight.

The results demonstrate a rather complex pattern of interaction between dietary sterols in determining the variables of the phenotype produced, under circumstances suggesting that all the sterols investigated have entered the developing larvae. There is only a partial overall correlation, and occasionally an inverse relationship, between tumour suppressant and growth-promoting properties of particular sterols. Within single molecules, structural sterol features tend to exert their characteristic effects additively upon the phenotype, except for an inadequacy in utilization of molecules containing the Δ7 double bond, which dominates at low concentrations. With pairs of dietary sterols, however, non-additive or ‘saving’ effects are sometimes seen.

It is suggested that the tu bw allele allows the resolution of several discrete developmental functions for sterols and/or their immediate metabolic products in Drosophila, which cannot synthesize its own sterol. However, the molecular nature of these functions is little understood.

Current molecular models of genetic recombination invoke steps mediated by deoxyribonucleases. It is likely therefore that some mutants deficient in these enzymes would have defective recombination mechnisms. Mutants of Ustilago maydis deficient in extracellular and intracellular DNase activity have been isolated. Three of the extracellular mutants are recessive and non-complementing, as are four of the intracellular mutants. The loci for extracellular and intracellular DNase deficiency have been named nuc-1 and nuc-2 respectively, and they are linked.

In crosses where each parent was deficient in both extracellular and intracellular DNase activity, meiotic allelic recombination (gene conversion) within the nar locus was abolished, although crossing-over in one tested interval was apparently normal in frequency. In DNase-deficient diploids, no mitotic allelic recombination in the nar locus was observed and the distribution of crossing over was abnormal. Nuclease deficiency did not appear to have any strong effect on radiation sensitivity.

A simulation study was undertaken of methods of subdividing populations into several small sublines and utilizing the variances generated between lines by selecting among them. Crosses of chosen lines were made, and either selection was continued in a single large population (single cycle) or the population was subdivided again (repeated cycles). As a control for the efficiency of these schemes, a single large population was maintained and selected at the same intensity from the outset. Simple models were used of additive or completely dominant genes, usually of equal effect and equally spaced on a single chromosome.

The single and repeated cycle structures give similar results, but the repeated cycle structure is more extreme.

With additive models intense selection between lines gives short-term advances, but causes a reduction in the limit when compared with a single population. The effect on the limit is greatest with free recombination, very small with complete linkage. If no selection is practised between lines the limit is unaffected, but takes longer to attain.

With complete dominance, and the recessive allele initially at low frequency, greater responses from selection are obtained within sublines than in the large population, large gains are made from selection between sublines, and a higher limit can be reached. If the recessive allele is at high initial frequency the subdivision is not beneficial.

Some simple theory is developed to explain these results. It is concluded that subdivision and crossing schemes are unlikely to be very useful except for elimination of deleterious recessive genes.