The effect of sub-dividing a population during selection was studied by selecting downwards for sternopleural bristles in Drosophila melanogaster. The four structures used all involved the selection of 40 individuals out of 200 measured in each sex. The alternatives were:

(i) one large line with the same selection procedure in all generations,

(ii) eight small lines with the same procedure in all generations,

(iii) the ‘single cycle’ structure in which large lines derived from crosses between selected small lines at either the sixth or twelth generation, and,

(iv) the ‘repeated cycle’ structure in which the best five small lines were mixed at the sixth generation of selection to produce a new set of small lines on which the procedure was repeated for a total of three cycles.

Of the first two methods, the large line had a higher final response than did any of the small lines. The latter, selected with an intensity of 5 out of 25 in each sex, had lower average final response than had a similar group of lines selected from the same base population with the lower intensity of 10/25. The results showed no clear effect of the sub-dicision of the population, followed by selection between lines, though they were in general agreement with theortical expectations. Several second chromosome recessive lethals were found at high frequencies in different selected lines. One of these, found in eight of the lines, had an effect on bristles in the heterzygote of about 1·5 phenotypic standard deviations. The evidence strongly suggests a pleiotropic effect on bristle score.

The genotypes are given of over 4500 asci showing aberrant segregation at the grey (g) spore colour locus in Sordaria fimicola from crosses, with outside markers present, between g locus mutants and wild type, or involving pairs of g locus mutants that differed in spore colour (g locus mutants range from grey to hyaline). This colour difference enabled asci with aberrant segregation of the mutant spore colours to be detected in the two-point crosses, as well as those with wild-type (black) spores. From a total of 21 one-point crosses involving altogether seven primary and two secondary g locus mutants, 2700 aberrant asci have been grouped into the 14 ascus genotypes that can be recognized, and in the two-point crosses 1830 asci (1044 fully scored) from 10 pairwise combinations of the mutants have been classified into the 150 ascus genotypes that can be distinguished.

Salivary-gland chromosomes of 54 methyl methanesulphonate- and 50 triethylene melamine-induced X-chromosome recessive lethals in Drosophila melanogaster were analysed. Two of the lethals induced by the mono-functional agent and 11 of those induced by the polyfunctional agent were found to be associated with detectable aberrations. A complementation analysis was also done on 82 ethyl methanesulphonate- and 34 triethylene melamine-induced recessive lethals in the zeste-white region of the X chromosome. The EMS-induced lethals were found to represent lesions affecting only single cistrons. Each of the 14 cistrons in the region known to mutate to a lethal state was represented by mutant alleles, but in widely different frequencies. Seven of the TEM-induced lethals were associated with deletions, only one of which had both breakpoints within the mapped region. Twenty-six of the 27 mutations in which only single cistrons were affected were mapped to 7 of the 14 known loci. One TEM- and two EMS-induced mutations were alleles representing a previously undetected locus in the zeste-white region.

It is shown that, in a finite population, by ensuring an equal contribution of offspring from each family we achieve a higher selection limit than by using mass selection, given that the correlation between selection criterion and additive genetic value is sufficiently high. The difference between the selection limits of the two schemes increases with more intense selection. The theoretical results were verified by Monte Carlo Simulation, and the influences of several factors were investigated. It is shown that such a breeding scheme might be useful in dairy cattle.

The possibility that changes in latent viruses would contribute to the differentiation of sublines in inbred strains of mice was investigated using the Bittner virus and the BALB/c strain of mice. The results show that, at least for this combination, there is no reason for implicating latent viruses in subline differentiation.

Interallelie crosses of mutants at the grey (g) spore colour locus in Sordaria fimicola, heterozygous for flanking markers, give rise to a large number of aberrant ascus genotypes, 45 of which can arise through relatively simple events and have been chosen for study. These genotypes comprise 50–75% of the aberrant asci, depending on the mutants crossed.

Comparison of the results from 10 pairwise crosses involving 7 alleles reveals that linked postmeiotic segregation and co-conversion decrease rapidly in frequency with increasing separation of the mutant sites.

The data from reciprocally recombinant asci, from asci with normal segregation at one of the two mutant sites, and from flanking marker behaviour in one- and two-point crosses, agree with the Holliday-Sobell formulation, with the following additional features:

(1) The nuclease, which nicks homologous polynucleotides and then degrades one of the two nicked chains when a mutant enters the hybrid DNA structure, can show preferential degradation of the mutant (or the wild-type) chain. In addition, a second nuclease is involved in the excision-repair process that introduces an additional preferential (marker specific) bias in the degradation of the mutant (or the wild-type) chain. This could explain why asci with odd-ratio conversion (5:3 and 3:5 ratios) sometimes show a different bias, as first reported by Emerson for Ascobolus, from those with even-ratio conversion (6:2 and 2:6 ratios), since the latter but not the former require, in addition, the action of a mismatch correction enzyme to account for them.

(2) The migratory hybrid DNA structure which enters the gene at one end may be of a different size from that which enters from the other end.

(3) Mismatch correction at the end of the hybrid DNA structure leads to a non-recombinant outside marker genotype and modifies the 1:1 ratio of parental:recombinant flanking markers that is otherwise found.

For large population sizes, gene frequencies p and q at two linked over-dominant loci and the linkage disequilibrium parameter D will remain close to their equilibrium values. We can treat selection and recombination as approximately linear forces on p, q and D, and we can treat genetic drift as a multivariate normal perturbation with constant variance-covariance matrix. For the additive-multiplicative family of two-locus models, p, q and D are shown to be (approximately) uncorrelated. Expressions for their variances are obtained. When selection coefficients are small the variances of p and q are those previously given by Robertson for a single locus. For small recombination fractions the variance of D is that obtained for neutral loci by Ohta & Kimura. For larger recombination fractions the result differs from theirs, so that for unlinked loci r2 ≃ 2/(3N) instead of 1/(2N). For the Lewontin-Kojima and Bodmer symmetric viability models, and for a model symmetric at only one of the loci, a more exact argument is possible. In the asymptotic conditional distribution in these cases, various of p, q and D are uncorrelated, depending on the type of symmetiy in the model.

Many of the yellow alleles found in Drosophila melanogaster result in a unique pattern of phenotypic expression. These patterns follow the morphologically distinct cell types of the cuticle, so that for one allele all the bristles of the head and thorax might be mutant, while most of the fly appears wild type. A comparison of many different y mutants demonstrates that the yellow phenotype is expressed independently in most if not all the different cell types which form the cuticle. Control of this expression appears to reside at the yellow locus itself.

We have studied the effects on fitness of allelic variation at three gene loci (Est-5, Odh, and Mdh-2)coding for enzymes in Drosophila pseudoobscura. Genotype has a significant effect on fitness for all six parameters measured (female fecundity, male mating capacity, egg-to-adult survival under near-optimal and under competitive conditions, and rate of development under near-optimal and under competitive conditions). No single genotype is best for all six fitness parameters; rather, genotypes with superior performance during a certain stage of the life-cycle may have low fitness at some other stage, or in different environmental conditions. Heterozygotes are sometimes best when all fitness parameters are considered. There are significant interactions between loci. The various forms of balancing selection uncovered in our experiments may account for the polymorphisms occurring in natural populations of D. pseudoobscura at the three loci studied.

The high XO production in Bpa+ mouse stocks appears to be due, not to Bpa itself, but to a closely linked factor for high XO production (Fxo) which may be a gene or a chromosomal aberration. The change of Bpa Fxo to Bpa non-Fxo occurs with a frequency of about 6%; the reciprocal change from Bpa Fxo to Fxo non-Bpa has not been found. There is some evidence that Fxo might involve a structural alteration such as an inversion or a deletion. The X-chromosome loss is due to non-disjunction which occurs in about one-third of the oocytes, probably mainly at meiosis I. Frequencies of other chromosomal abnormalities found in the stocks are given.

Selection for high and low growth-rate was carried out during eight generations of asexual propagation by zoospores and seven generations of sexual reproduction by oospores. The fungus has previously been shown to be diploid during its vegetative phase. In the zoospore lines there was no significant variation and no response to selection, except for the occasional appearance of fast-growing sectors. A high line was established from such a sector; in its sexual progeny the inheritance of growth-rate was non-Mendelian. Propagation through self-fertilized oospores released very considerable genetic variation, and both high and low lines responded to selection. At first the variation within families, and the response to selection, increased with succeeding generations, despite the intense inbreeding. In later generations the high line became less variable, and the progeny oospore cultures resembled the fast-growing sectors. It is concluded that growth-rate is controlled by a polygenic system and by cytoplasmic determinants, a mutant form of which is responsible for the fast-sectoring phenotype.

This paper is devoted to the study of the effects of population subdivision on the evolution of two linked loci. Two simple deterministic models of population subdivision without selection are investigated. One is a finite linear ‘stepping stone’ model and the other is a finite linear stepping stone chain of populations stretching between two large populations of constant genetic constitution. At equilibrium in the first model the gene frequencies in each population are equal and there is linkage equilibrium in each population. The rate of decay to zero of the linkage disequilibrium functions is the larger of (1 – c) and , where λ1 is the rate of convergence of the gene frequencies to equilibrium and c is the recombination frequency. In the second model at equilibrium there will be a linear cline in gene frequencies connecting the two large constant populations. This cline will be accompanied by a ‘cline’ of linkage disequilibria. The rate of convergence to this equilibrium cline is independent of the recombination frequency, and, in fact, the gene frequencies and the linkage disequilibria converge to equilibrium at the same rate.

Clones of V79 Chinese hamster cells resistant to the steroid compound ouabain have been induced by mutagen treatment with MNNG (= N-methyl-N′-nitro-N-nitrosoguanidine). The frequency of resistant colonies was increased from spontaneous value of 2 × 10−6 to a frequency of 1·2 × 10−3 with MNNG treatment.

The highest number of induced mutants appeared when an expression time pf 40 h was allowed between MNNG treatment and addition of ouabain.

We propose a general hypothesis involving properties of circular DNA which can explain such phenomena as the petite mutation, suppressiveness, and the polarity observed in mitochondrial recombination in the yeast Saccharomyces cerevisiae. This hypothesis involves excision and insertion events between circular DNA molecules as well as structural rearrangements in the DNA generated by these events. The special properties of circular DNA have been considered in analysing recombination, and a number of results are obtained which are not intuitively apparent.

This hypothesis can be applied to any situation involving circular DNA such as bacterial plasmids and cytoplasmic circular DNAs, where the opportunity exists for recombination and rearrangement events.

The larvae of Drosophila melanogaster feed continuously during their period of development. The rate of feeding activity, measured as the number of cephalopharyngeal retractions per minute, varies with the physiological age of the larva. Feeding rate responded readily to directional selection to give rise to non-overlapping populations with fast and slow feeding larvae, respectively. Realized heritabilities for the character from different selected lines varied between 11 and 21%. Crosses between the selected populations show significant dominance for fast feeding rate and appreciable non-allelic gene interaction. Larvae of the slow feeding populations showed a correlated reduction in locomotor activity but fast feeding larvae do not move about significantly faster than the unselected controls. Asymmetry of the correlated response to selection, it is argued, is due to selection in the slow feeding populations of alleles with a secondary effect in both behaviours.

Amoebae of the Colonia isolate of Physarum polycephalum produce plasmodia within individual amoebal clones.

This paper reports the derivation from the Colonia strain C50 of a strain CL (Colonia Leicester) which produces plasmodia in clones with high efficiency and which completes the life cycle reliably and repeatedly in single clones. The derivation of a line CLd (CL delayed plasmodium formation) is described and, using CLd, the construction of the isogenic heterothallic strains mt1; CL and mt2; CL.

The above strains provide a system for the isolation and genetic analysis of mutants of P. polycephalum within a uniform genetic background, in particular mutants expressed in the plasmodium.

Using this system two auxotrophic mutants have been isolated. Preliminary genetic analysis has shown that they are due to single gene mutations.

A new metric character in mice, ‘footpad bristle number’ is described. The character is easily measured under a stereo-microscope, is very highly inherited, and is independent of age, sex and the environment common to littermates. Such a character might prove useful in a number of quantitative genetic studies in mice.

In order to detect regulatory genetic sites in the autosomes of Drosophila melanogaster, the levels of X-linked glucose-6-phosphate dehydro-genase and autosomally linked α-glycerophosphate and isocitrate dehydrogenases have been monitored in extracts of flies aneuploid for regions of chromosomes II and III. In addition to expected structural gene dosage responses of α-GPDH and IDH, flies hyperploid for several autosome regions were found to display altered levels of one or more of the enzymes studied. While IDH activity was increased in flies hyperploid for segments of both chromosomes II and III, α-GPDH activity was decreased in specific hyperploids for chromosome II regions only. The latter group of segmental aneuploids were normal with respect to levels of chromosome II-linked alcohol dehydrogenase. To test if the observed responses were due to dosage changes of discrete genes lying within the larger effective segments, flies aneuploid for subdivisions of the chromosome segments 21A-25CD, 35A–40, and 70CD–71B were assayed. For two of these large segments so analysed, the apparent effects were attributable to specific small subdivisions, suggesting the presence of discrete regulatory sites within the latter. For the 35A–40 region the α-GPDH effect observed for subdivisions was not sufficient to account for the large α-GPDH decrease seen in flies hyperploid for the large, inclusive region. These observations are discussed with respect to the possible bases of effect of regulatory elements on enzyme activity.

Klebsiella aerogenes V9A contains two lac operons, one chromosomal and one borne by the Lac plasmid, FKlac. It is shown that the plasmid Lac repressor resembles that of Esherichia coli in that it represses the E. coli operon but is inactivated by melibiose. In contrast, the chromosomal Lac repressor of V9A is unable to repress the E. coli operon or the FKlac operon, but is converted into an active repressor of both these operons on becoming bound to melibiose. The chromosomal Lac repressor is able to repress its own operon whether or not it is bound to melibiose, but is inactivated by isopropyl-β-D-thiogalactoside. These results support the hypothesis that the Klebsiella Lac plasmid was derived from an ancestral E. coli chromosome.

The genetic control of the sterility of male hybrids between certain laboratory and wild mice (Mus musculus L.) is investigated. The observed sterility is, by definition, hybrid sterility since both parental forms (i.e. wild and laboratory mice) are fully fertile, their male offspring displaying small testes with arrest of spermatogenesis at the stage of spermatogenesis or primary spermatocytes. Results of genetic analysis as well as the failure to detect any chromosomal rearrangements point to a genie rather than a chromosomal type of hybrid sterility.

Fifty-three wild males were classified into three sets, after mating with C57BL/10 inbred females, according to the fertility of their male progeny (set I – only sterile sons; set II – only fertile sons; set III – both fertile and sterile sons). The wild males of set I, which yield only sterile male offspring with C57BL/10 females, sire sterile sons also with females of the following inbred strains: A/Ph, BALB/c, DBA/1, and AKR/J, whereas the same wild males produce fertile offspring with females of C3H/Di, CBA/J, P/J, I/St and F/St inbred strains.

The described hybrid sterility seems to be under the control of several independently segregating genes, one of them (proposed symbol Hst-1) being localized on chromosome 17 (linkage group IX), 6 cM distally from dominant T (Brachyury). A chance to search for the mechanism of hybrid sterility is provided by the finding of two laboratory inbred strains, C57BL/10 and C3H/Di, differing with respect to the Hybrid sterility genetic system only at the Hst-1 gene.

Hst-1 is closely linked but apparently not identical with the sterility factor of recessive t alleles of the T locus.