An amber mutation was created in the CAT gene of plasmid vector pACYC184 and this modified plasmid was fused with the Streptomyces vector pIJ702 for use as an indicator for the identification of Streptomyces strains carrying nonsense suppressor tRNA mutations. The resulting hybrid plasmid pGM1109 was introduced into the chloramphenicol-sensitive mutant M252 of Streptomyces lividans. Chloramphenicol-resistant colonies were isolated and characterized. None of them was a nonsense suppressor mutant. The failure to obtain such mutants is discussed on the basis of codon usage in streptomycetes.

Within-line heterogeneity has been found in the mitochondrial DNA (mtDNA) in two isofemale lines of D. simulans. The co-existing types, S and M, were typical of the mtDNA in D. simulans and in D. mauritiana, respectively, their nucleotide divergence per site being ca. 2·1%. Segregation analysis confirmed that some individuals in these lines were heteroplasmic and suggested incomplete maternal inheritance of mtDNA in Drosophila. Examination of other lines of D. simulans revealed that the M type of D. mauritiana occurs at 71% in Réunion, 38% in Madagascar and 0% in Kenya. This finding and interspecific sequence comparisons of both M types indicate that D. mauritiana diverged from D. simulans probably less than 240000 years ago.

Genetic exclusion is the ability of a primary infecting phage to prevent a secondary infecting phage from contributing its genetic information to the progeny. The molecular mechanism of the phenomenon is not well understood. The two genes in phage T4 mainly responsible for genetic exclusion are the immunity (imm) gene and the spackle (sp) gene. Evidence is presented that the imm gp enables the host exonuclease V to degrade superinfecting phage DNA. This appears to be accomplished by the imm gp altering gp 2/64, the presumed pilot protein, which protects the 5′ end(s) of the phage DNA. Exonuclease III is also involved in genetic exclusion but its action does not appear to depend upon the imm or sp gene products. Gp sp appears to interfere with the lysozyme activity of gp 5, a component of the central base plug, postulated to aid in tail tube penetration during the injection process. A molecular model of genetic exclusion is proposed. Genes imm and sp are part of a cluster of genes which also includes 42, beta-glucosyltransferase, and uvsX. The genes of this cluster encode proteins apparently adapted for competition and defence at the DNA level. These genes may encode fundamental adaptive strategies found throughout nature.

Phycomyces blakesleeanus wild-type NRRL1555( − ), the standard strain, when crossed with UBC21( + ), another wild type, gives zygospores that germinate in 50–60 days. By backcrossing to UBC21 and selecting for shorter dormancy we have isolated a ( − ) strain, A803, and a ( + ) strain A804, which when crossed give zygospores that germinate in 32 days, the shortest dormancy period found in Phycomyces. The same result was obtained when A803 was crossed with UBC21. Zygospore dormancy decreased as the parental strains became more isogenic with UBC21, but the number of zygospores giving germsporangia with viable germspores also decreased to zero in the third backcross. The existence of germspore-killer alleles in the strain UBC21 is postulated. The strains of shortest dormancy can be used as helper strains (Orejas et al. 1985) in sexual crosses. Tetrad analysis of the cross NRRL1554 × S102, a two-factor cross, showed 90% of reciprocal ditypes plus tetratypes in the progeny, indicating that the ( + ) wild-type strain NRRL1554, when crossed with the standard strain, gives regular meiosis and, contrary to current beliefs, may be used in Phycomyces genetic analysis.

The DNA structures around the G6PD coding region in three high-G6PD activity mutants and their low-activity revertants of Drosophila melanogaster were analysed by Southern blot using a cloned G6PD gene as a probe. As a result, two kinds of insertion sequences were found; one was present just 5′ to exon I (Ins1), and the other within the intron (Ins2). The Ins1 sequence was 3·5 Kb in two mutants and 2·9 Kb in one mutant. In both cases, it consisted of a core sequence either 1·2 or 0·6 Kb long flanked by terminal repeats. On the other hand, low-activity revertants possessed either a defective Ins1 or no Ins1. The Ins2 sequence was found in all mutants and revertants, but not in Canton S. Although a recombinant phage carrying the DNA fragment spanning the entire Ins1 has not been obtained, sequencing data of the clone containing only the terminal repeats demonstrated that the repeats are defective P elements. Comparison of the genomic DNA structures of mutants and revertants suggested that the element responsible for the positive regulation of the G6PD gene in the mutants would probably be the core sequence, but not the flanking defective P elements. It was also conjectured that the 1·2 Kb core sequence might be composed of two identical elements, which might transpose independently.

Restriction site analysis revealed a variant growth hormone gene haplotype fixed within growth-selected mice (High line-3; HL-3) exhibiting growth rates 1·5 times greater than those of unselected Foundation population (FP-3) mice. Relative to the FP-3 haplotype, the HL-3 haplotype exhibited restriction fragment length polymorphisms for each of seven different restriction enzymes. Three of the polymorphic sites lie within 1·1 kb of the 5′ end of the structural gene; a fourth polymorphism exists within the structural gene. The HL-3 haplotype was also fixed within an additional three growth-selected lines (including a replicate of HL-3). This identification of an association, between the natural variant of a growth regulating gene and a growth-related phenotype, is the prototype of experiments that could lead to the isolation of variant genes which enhance livestock production characters.

In this study we estimate the frequency at which P-element insertion events, as identified by in situ hybridization, generate lethal and mild viability mutations. The frequency of lethal mutations generated per insertion event was 0·004. Viability dropped an average of 1% per insertion event. Our results indicate that it is deletions and rearrangements resulting from the mobilization of P elements already in place and not the insertions per se that cause the drastic effects on viability and fitness observed in most studies of P–M dysgenesis-derived mutations. Elements of five other families (I, copia, 412, B104, and gypsy) were not mobilized in these crosses. Finally, we contrast the density of P elements on the X chromosome with the density on the four autosomal arms in a collection of thirty genomes from an African population. The relative number of P elements on the X chromosome is too high to be explained by either a hemizygous selection or a neutrality model. The possible reasons for the failure to detect selection are discussed.

Using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), the genetic variation of proteins was investigated in three organs (mesocotyl, sheath and blade of second leaf) from two maize lines and their hybrids. Nine hundred and eighty-six spots were numbered over the three organs. One hundred and fifty-five polypeptides were found to be genetically variable, due to allelic polymorphism of structural genes and/or to polymorphism of any genetic elements controlling protein amounts. Of these 155 variants 12% clearly showed complete dominance effects in the hybrid patterns, which could reveal dominance effects in the regulation of the protein biosynthesis. Comparison of the three organs showed that (i) the level of variability between lines depended upon the organ, since it varied from 7·5% for the blade to 12·6% for the mesocotyl and 13·2% for the sheath; (ii) 68 polypeptides displayed different kinds of variation in different organs and (iii) in all cases but one the dominant inheritance was organ-specific.

The role of epistatic interaction of allozymes in the determination of variation in larval ethanol tolerance of Drosophila melanogaster was examined. Isofemale lines from the Tahbilk Winery were made homozygous for different common alleles of alcohol dehydrogenase (Adh) and sn-glycerol-3-phosphate dehydrogenase (Gpdh). When fed 6% ethanol, all the lines had reduced survival and, in the survivors, reduced body weight and lengthened development time. A strong positive correlation between tolerance and development time suggested that alleles responsible for slowing development on ethanol also increased ethanol tolerance. Analysis of larval ethanol tolerance over four generations showed that larvae of the AdhffGpdhff, and AdhssGpdhss allelic combinations were more tolerant than larvae with the other combinations. However, these genotypes were not associated with the slowing of development nor the weight loss on ethanol. Hence, larvae with certain combinations of Adh and Gpdh allozymes may have a greater capacity to metabolize ethanol and be more tolerant to its toxic effects.

One hundred and ninety-eight mice trapped along a south–north transect through the Danish hybrid zone between Mus musculus domesticus and M. m. musculus were typed for mitochondrial DNA (mtDNA), the Y chromosome and ten autosomal loci encoding diagnostic proteins. The southern (domesticus) populations display two mtDNA variants (S1 and S2) and the northern (musculus) have a third mtDNA variant (N) of domesticus origin. Across the hybrid zone defined by ten autosomal loci, there is a steep dine between the southern and northern types of mtDNA. As well as confirming an earlier finding that Danish musculus all have a domesticus mtDNA (Ferris et al. 1983a, & b), our results show that this mtDNA takeover is not the result of a persistent mitochondrial gene flow between the two subspecies. While the coincident dines for the ten autosomal loci and the abrupt dine for the Y chromosome can be explained by selection, it is less likely to be the case for the mtDNA exchanges. We discuss the possible role of sex-linked migration and genetic drift to account for the distribution of the mitochondrial variants.

A recessive autosomal mutation has been found in the CXBI/ByEss recombinant-inbred line but in neither of the parental strains, C57BL/6ByEss and BALB/cByEss. Its presence in the CXBI/ByJax and CXBI/ByLac sublines suggests an origin early in inbreeding. The locus, seminal vesicle shape (svs), appears to be linked to the albino locus on chromosome 7. The homozygote has seminal vesicles with a smooth tubular external appearance. In segregating crosses homozygotes had slightly lighter seminal vesicles but the weights of other androgen target organs were not reduced. Exogenous testosterone increased the size of the seminal vesicles but did not alter their shape. The mutation did not affect the pattern of proteins on SDS–acrylamide gel electrophoresis, which did differ between the parental strains. The locus affecting a 27000 Da protein has provisionally been assigned the symbol svp-4.

In this study we genetically analyse a large autosomal region (23 map units) in Caenorhabditis elegans. The region comprises the left half of linkage group V [LGV(left)] and is recombinationally balanced by the translocation eT1(III; V). We have used rearrangement breakpoints to subdivide the region from the left end of LGV to daf-11 into a set of 23 major zones. Twenty of these zones are balanced by eT1. To establish the zones we examined a total of 110 recessive lethal mutations derived from a variety of screening protocols. The mutations identified 12 deficiencies, 1 duplication, as well as 98 mutations that fell into 59 complementation groups, significantly increasing the number of available genetic sites on LGV. Twenty-six of the latter had more than 1 mutant allele. Significant differences were observed among the alleles of only 6 genes, 3 of which have at least one ‘visible’ allele. Several deficiencies and 3 alleles of let-336 were demonstrated to affect recombination. The duplication identified in this study is sDp30(V;X). Lethal mutations covered by sDp30 were not suppressed uniformly in hermaphrodites. The basis for this non-uniformity may be related to the mechanism of X chromosome dosage compensation in C. elegans.

Position-effect variegation is a phenomenon in which cell-autonomous genes, normally expressed in all cells of a tissue, are expressed in some cells but not in others, leading to a mosaic tissue. Variegation occurs when a normally euchromatic gene is re-positioned close to heterochromatin by chromosome rearrangement. The extent of variegation is known to be influenced by a number of environmental and genetic factors. In the courss of investigations of the influence of the pH of larval medium on the extent of eye-colour variegation in In(1)ωm4 Drosophila melanogaster, we have found that the extent of variegation depends on development time. Flies reared at pH 2·6 develop slowly and show more extreme variegation than those reared at higher pH. This effect, as well as variations within the pH treatments, can be accounted for by differences in development time. The observed regression relationship between variegation and development time also appears to accommodate the influences of temperature on both variables. We suggest that development time may account causally for the reported influences of a number of environmental agents (temperature, crowding, chemicals) on variegation. Ways in which this might occur are discussed in the context of models of the molecular basis of differential gene activity.

Models of variability in quantitative traits maintained by a balance between mutation and stabilizing selection are investigated. The effects of mutant alleles are assumed to be additive and to be randomly sampled from a stationary distribution. With a two-allele model the equilibrium genetic variance in an infinite population is independent of the distribution of mutant effects, and dependent only on the total number of mutants appearing per generation. In a finite population, however, both the shape and standard deviation of the distribution of mutant effects are important. The equilibrium variance is lower when most of the mutational variance is contributed by few genes of large effect. Genes of small effect can eventually contribute substantially to the variance with increasing population size (N.) The equilibrium variance can be higher in a finite than an infinite population since near-neutral alleles can drift to intermediate frequencies where selection is weakest. Linkage leads to a reduction in the maintained variance which is small unless linkage is very tight and selection is strong, but the reduction becomes greater with increasing N since more mutants segregate. A multi-allele model is simulated and it is concluded that the two-allele model gives a good approximation of its behaviour. It is argued that the total number of loci capable of influencing most quantitative traits is large, and that the distribution of mutant effects is highly leptokurtic with the effects of most mutants very small, and such mutants are important in contributing to the maintained variance since selection against them is slight. The weakness of the simple optimum model is discussed in relation to the likely consequences of pleiotropy.

A low activity mutant of glucose-6-phosphate dehydrogenase, G6pda-m1Neu has been used to position G6pd in the mouse X chromosome. Linkage tests with tabby, Ta and harlequin, Hq, indicate a likely gene order of Hq–G6pd–Ta. Muscular dystrophy, mdx, has been located by two-and three-point crosses using Hprt, Pgk-1 and Moblo and suggest a gene order of Hprt–mdx–Pgk-1–Moblo. Together with existing linkage data a tentative order for the seven loci is Hq–Hprt–G6pd–mdx–Ta–Pgk-1–Moblo. The relative positions of G6pd and mdx have not been directly tested and G6pd is assigned provisionally proximal to mdx. In the three point test using Hq, G6pd and Ta the recombination frequency found between Hq and Ta was 9·9 ± 2·6%, substantially less than the value of 20·5 ± 2·1% reported by Isaacson et al. (1974).

Two hitherto unmapped recessive autosomal mutations, ‘arrested development of righting response’ (adr) and ‘myotonia’ (mto, now adrmto), were found to be allelic, so that preliminary linkage data on adr and adrmto can now be combined. No linkage was found to the glucose phosphate isomerase (Gpi-1) locus on Chr 7 that marks a region of homology between mouse Chr 7 and human Chr 19, and in man is closely linked to the myotonic dystrophy (DM) gene. The adr gene was expressed on diverse genetic backgrounds including the athymic nude mouse.

Twenty autosomal dominant cataract mutations were detected among the offspring of male mice irradiated with γ- or X-rays. The single or fractionated doses ranged from 5.34 to 10.2 Gy. The phenotypic manifestation and penetrance of the mutations as well as fertility and viability of the mutants were studied by extensive breeding. Manifestation of 4 mutations was limited to the lens. Sixteen mutations were characterized by multiple ocular anomalies, of which 4 mutations also affected other organs of the body. Seventy per cent of the mutations caused severe opacity of the lens or lens and cornea. Homologous hereditary diseases in man would be juvenile cataracts with serious impairment of vision or blindness. Expressivity of the lens opacities was almost constant whereas the accompanied defects varied with respect to their severity in different individuals as well as in eyes of an individual. Phenotypic differences dependent on the genetic background could not be observed. Fourteen mutations were classified as mutations with complete penetrance without any effect on viability and fertility of heterozygotes. Four other mutations were shown to be fully penetrant but the viability of the heterozygotes was impaired. Two mutations had incomplete penetrance with no viability or fertility effects. Of the 14 mutations with complete penetrance and normal viability and fertility 6 were shown to be homozygous viable, 1 semi-lethal and 7 lethal.

Mice which are either homozygous or heterozygous for the CatFraser mutation have ocular cataracts accompanied by selective reduction of the γ-crystallins, a homologous family of proteins present in the lens and encoded by a family of tightly linked genes. We measured the concentrations of four different mRNAs, each encoding a different γ-crystallin, in the lenses of homozygous CatFraser mice and in normal controls at various stages of development by preparing Northern blots from lens RNA, probing with RNAs complementary to each of the four messages and densitometry of the bands thus generated. The results show that, for each of these messages, the ontogenetic patterns observed in normal mice are retained in the mutant, but at much lower concentrations.

A mutant strain of Drosophila melanogaster with five markers on the X-chromosome was found to be more sensitive than the wild type when infected with an insect-pathogenic strain of Serratia marcescens. Two of the five mutations in this fly strain, cut and miniature, were found to be responsible for this sensitivity. A double-mutant, with both cut and miniature, was as sensitive to Serratia infection as was the original sensitive Drosophila strain with all five mutations. Recombinant flies with other alleles of cut and miniature were also sensitive. A revertant of cut was found to be less sensitive than the parental flies. Our insect pathogenic strain of Serratia produces several proteases and a chitinase. A bacterial mutant, lacking proteases and chitinase, was found to be less virulent than wild-type bacteria. When pupal shells from resistant and cut-miniature flies were incubated with a mixture of protease and chitinase there was a release of N-acetyl glucosamine, and 50% more material was liberated from pupal shells of sensitive flies. Sensitive flies reared on sucrose infected with Serratia showed bacteria in their hemolymph earlier than wild-type flies. We conclude that Drosophila genes for cut and miniature are associated with the sensitivity to Serratia infection, presumably because the gut peritrophic membrane is more susceptible to bacterial proteases and chitinase.

Glycine tastes both bitter and sweet to mice but there are differences between strains in their ability to detect each taste. With respect to the bitter taste, fifteen strains were classified as tasters and twelve strains as non-tasters. The difference is due to a single gene, Glb (glycine bitterness). Cycloheximide tastes bitter to all mice at a concentration of 8 μM, but strain differences in sensitivity to the taste of cycloheximide can be detected at lower concentrations. The BXD RI strains can be classified into two groups with respect to sensitivity to cycloheximide. This is probably due to the segregation of two alleles of a single gene, Cyx. A comparison of the distribution in RI strains of alleles of four bitterness-tasting genes shows that the loci are all closely linked and are probably in the order Cyx–Qui–Rua–Glb.