An allotypic specificity (A1) of sheep serum is described. The antigenic determinant is located on a low molecular weight glycoprotein which has its isoelectric point at pH 5 and is capable of interacting with the lectin concanavalin A.

Family studies showed that the allotype is inherited in a simple Mendelian manner.

Four isolated populations of the skipper frog, Rana cyanophlictis were first studied in 1965 and then again in 1975. The genetical changes were measured by the incidence of 19 non-metrical skeletal variants. It was found that these populations have changed very little in 10 years, although the inter-population diversity, as judged by the estimates of divergence, is less now than previously. This could be due to the similar environmental conditions prevailing in Delhi and its neighbourhood from where these frog populations were collected.

A new method for the isolation of temperature-sensitive mutants of Physarum polycephalum is described. It involves enrichment and prescreening of mutagenized amoebae followed by screening at both the plasmodial and amoebal stage. A total of 74 temperature-sensitive strains were recovered of which 26 were temperature-sensitive only as plasmodia, 35 only as amoebae and 13 in both stages. After a shift to the nonpermissive temperature, DNA and protein synthesis were followed in temperature-sensitive plasmodia to discover if the lesion affected functions of the nuclear cycle.

Genetic variation contained in a multigene family was theoretically investigated from the standpoint of population genetics. Unequal crossover is assumed to be responsible for the coincidental evolution of mutant genes in a chromosome. When the allowed latitude of the duplicated or deleted number of gene units at unequal crossover is 10 ˜ 15% of the total gene number in a chromosome, the arrangement of gene lineage in a chromosome is shown to be roughly random. The equilibrium properties of genetic variation or the probability of identity of two genes within a family (clonality) were studied under mutation, unequal crossover, interchromosomal crossover and sampling of gametes. The clonality of a multigene family within a chromosome is shown to be approximately

in which α = 2k/n2 with k = effective number of cycles of unequal crossover and with n = number of gene units in a family, v is the mutation rate per gene unit, β is the rate of interchromosomal crossover per family and Ne is the effective size of the population, all measured by the rate per generation. The clonality of a gene family between two different chromosomes becomes approximately C1 = C0/(l + 4Neν). Some models of natural selection which lowers the clonality or increases genetic variation in a multigene family were investigated. It was shown that natural selection may be quite effective in increasing genetic variation in a gene family.

Hydroxyurea (HU) effectively inhibits meiosis in Schizophyllum. The predominant cytological stage in inhibited fruit bodies is fusion. The inhibition is reversible and makes possible synchronization of a naturally nonsynchronous system. Microphotometric determinations of the DNA content in prefusion nuclei treated with HU suggest that premeiotic DNA replication occurs in prefusion nuclei. Synaptinemal complexes are not completed in HU-treated nuclei, suggesting that this event is dependent on premeiotic DNA replication.

The alcohol dehydrogenase-1 gene in maize presents advantages for mutational analysis. Foremost among these is the ability to chemically select ADH-negative and ADH-low gametophytes owing to their resistance to allyl alcohol vapour. Immature tassels were irradiated with either 220 kV X-rays or 400 MeV/amu accelerated neon-ions; spontaneous mutants were also selected and recovered. RBE for neon-20 was about 5. A total of 70 presumptive mutants were placed into one of four classes on the basis of allozyme profiles following electrophoresis and ADH staining: (A) dysfunction, (B) underproducer, (C) overproducer, and (D) up-Adh2 gene. Mutants have been recovered and confirmed in the first three classes. These include two male-transmissible deletion-type lesions induced by X-rays, five underproducer transpositions and one overproducer transposition induced by neon-20. Certain of the neoninduced alleles are unstable in their expression. All 70 mutants are chromosomal aberrations; no intragenic lesions were recovered although our experimental design would have preferentially recovered them if they had occurred.

The Discussion considers the mutagenic action of ionizing radiation, and especially the well-documented differences between maize and Drosophila data. In particular, the effect of these chromosome derangements on the ‘programmable’ component(s) of the Adhl cistron is discussed.

The (I; II) duplication strain of Aspergillus nidulans contains a terminal segment of chromosome I twice, one copy being in the normal position, and the other one translocated to a tip of chromosome II. We show that in selfed cleistothecia (homozygous for the duplication) crossing-over between the two segments of the duplication followed by the appropriate disjunction and distribution of the meiotic chromosomes, results in segregation of recessive markers in the duplication. Alternative segregation mechanisms like the deletion mechanism responsible for mitotic non-conformity, cannot explain the observations. The average segregation frequency of the marker yA2 is 11%. Using the mathematical model outlined in the Appendix to this paper, we estimated the recombination frequency between the translocation breakpoint and the yA locus from the segregation frequency. The essential feature of the model is the computation of the probabilities of combinations of different tetrad types in quadrivalents. Application of the model leads to the qualitative conclusion that the meiotic recombination frequency within the duplication is increased over the normal level. Elsewhere in the genome the frequencies are either unchanged or decreased. Also in crosses heterozygous for the duplication, an increase by at least a factor of two is found. As judged from the appearance of certain recombinant classes, the quadrivalent frequency in homozygous and heterozygous crosses is 2/3 (random pairing) or slightly higher. The increased recombination is attributed to the same lesions that are responsible for the occurrence of deletions in duplication strains of A. nidulans.

Combining data from mitotic crossing over in, and haploidization of, heterozygous diploid strains, 33 markers have been mapped successfully in Verticillium spp. One marker (Hyl), which determines the absence of darkly pigmented resting structures in many stable hyaline strains, showed an irregular segregation. In view of previous evidence from acriflavine treatment and heterokaryon analyses in the fungus, this further substantiated indications of a cytoplasmic pattern of inheritance for this marker. The phenotypic expression of dark pigment genes showing nuclear inheritance, such as Sot., depends upon the cytoplasmically determined (Hyl+) presence of resting structures.

The influence of sodium octanoate on the polymorphism at the loci G6PD and 6PGD in Drosophila melanogaster was investigated by studying its effect on egg hatchability, larval-to-adult survival and adult survival. The results demonstrate the existence of differences in fitness between the different genotypes of the two loci both for larval-to-adult survival and for adult survival. Furthermore, changes in enzyme activity of both enzymes, brought about by the sodium octanoate treatment, were observed. This makes it highly probable that the observed differences in fitness can be ascribed to the loci themselves and not to linked fitness genes. Finally, this study demonstrates the existence of strong interaction between the two loci with respect to fitness. Epistasis was demonstrated both in the larval-to-adult survival experiment and in the adult survival experiment.

Models of two linked overdominant loci in moderately large, but finite, populations are examined by looking at the variance-covariance matrix of the two gene frequencies and the linkage disequilibrium around stable deterministic equilibrium points. In particular, the effect of genetic drift is examined in cases where, in infinite populations, two stable equilibria with non-zero linkage disequilibrium, D, are maintained. Theoretical formulae are produced and checked by computer simulation. In general, the results show that unless the population size is very large indeed, genetic drift causes the values of D to vary considerably about the equilibrium values and that for many models, where stable equilibria exist at non-zero D values, a wide range of values of D have a high probability. Thus it is very difficult to draw conclusions about the selection regime by measuring Linkage disequilibrium in a finite population.

Mice homozygous for the asebia mutation (ab/ab) are char1acterized by defective sebaceous glands, a short sparse hair coat from 7 days and progressive alopecia. In addition, we have found that the initial hair follicle rudiments in the skin of these mice are able to differentiate into relatively normal anagen follicles which are often excessive in length and have minor abnormalities of the inner and outer root sheath components. The inner root sheath fails to form the typical transverse corrugations at the level of the sebaceous glands and its cells apparently remain, partially undegraded, plugging the hair canal and adhering to emerging hair shafts. Defects noted in the outer root sheath may be responsible for the failure of inner root sheath degradation. With increasing age, irregularities in hair cycle duration, loss of the originally parallel arrangement of hair follicles and further abnormalities of the individual follicular components are increasingly evident. Follicles in asebic mice have a tendency to form buds and branches which occasionally begin typical follicular differentiation. The consistent failure of the asebic follicles to pass normally through the catagen stage to the telogen stage results in long twisted follicles with abnormal and often loosely anchored hair clubs. The dermal papillae are often abnormal or absent from telogen follicles, while typical germ cells are not formed. Thus the lack of multiple hair follicles, the disorganization of follicles and the progressive alopecia observed in the asebic mice are accounted for. It is suggested that the altered dermal environment and outer root sheath abnormalities may be responsible for many of the follicular defects.

Mice homozygous for the asebia mutation (ab/ab), which have defective sebaceous glands, display abnormalities in several other aspects of the integument. Histological sections showed that hyperplasia of the cellular layers and the stratum corneum of the epidermis is apparent at birth and increases markedly with age. Enlarged intercellular spaces are also noted in the epidermis. The thicker dermal layer of the asebic mice is characterized by increased vascularity, increased cellularity and the abnormal morphology of a large proportion of the ‘fibroblast’ population. Electron microscopy demonstrated the many abnormalities in the dermal fibroblasts as well as large amounts of cellular debris in the surrounding matrix. Collagen and elastin show alterations at the light microscopic and ultrastructural levels. Many features of the asebic dermis resemble those found with mild inflammation and with the lysosomal storage diseases. Changes in the dermis of asebic foetuses were noted prior to epidermal alterations and may mediate the latter.

Contrary to what their name asebia implies, mice homozygous for the ab gene do possess actively secreting sebaceous glands which develop normally from the follicular outer root sheath, at 18 days post-conception. However, by the 20th day post-conception, these mice exhibit the abnormal sebaceous cytodifferentiation which remains typical of the asebic glands throughout life. Nests of outer root sheath cells below the sebaceous glands also undergo atypical sebaceous differentiation. The smooth membrane system and mitochondria, which appear to be responsible for the orderly accumulation of lipid droplets and sebum production in normal mice, become increasingly abnormal in asebic mice. Fewer lipid droplets form, the smooth endoplasmic reticulum becomes distorted and dilated, and the normal transformation of mitochondria does not occur. Atypical differentiation occurs randomly and ‘differentiated’ cells often degenerate within the asebic sebaceous glands. Of the larger specialized sebaceous-type glands studied, only the Meibomian glands are similarly affected by the asebia mutation, while the anal and preputial glands appear to undergo a more normal cytological differentiation. The abnormalities seen in the asebic sebaceous glands seem to be due to defective regulation of the synthetic or degenerative processes necessary for completion of normal sebum production. Both the defects of sebaceous glands and the unusual characteristics of the epidermis and hair follicles in asebic mice may be initiated by the abnormal underlying dermis or the apparently abnormal endocrine system.

Homozygotes for recessive visible genes have often been discovered in lines under artificial selection, sometimes many generations from the start. As a help in the interpretation of this phenomenon, the distribution of the time to first detection as a homozygote of a recessive gene occurring only once in the initial generation has been obtained. Alternatively the results may be considered as referring to the time of first appearance as a homozygote of a new mutation occurring in a finite population. For a monoecious random mating population of size N with selfing permitted, the mean time to detection is very close to 2N⅓ over a range of N from 1 to 500 with a coefficient of variation of roughly 2/3 and a 95% upper limit about 2·5 times the mean. If selfing is prohibited, the mean time is increased by a little over 1 generation. The treatment is extended to cover the effects of artificial selection in favour of the heterozygote, of the frequency of occurrence in the initial generation and of the examination of more individuals each generation than are used as parents.

The combined effect of multi-niche selection and cyclical selection is studied in a deterministic model. Sufficient conditions for protected polymorphism are derived for diploid populations with and without dominance and for haploid populations. These conditions appear to be broader than in the cases of only multi-niche selection or only cyclical selection.

Analysis of tetraparental Hfr × F− matings of Escherichia coli strains showed that mating complexes were predominantly pairs or small aggregates of cells. Many physically associated complexes of donor and recipient cells gave rise to no recombinant cells. The observed linkage of genetic markers in recombinants is sensitive to multiple mating events, and should therefore be measured under well-defined conditions giving pairwise matings only.

The paper describes a cattle serum antigen (McA2) located on a macroglobulin molecule which has its isoelectric point at pH 5 and is capable of interacting with the wheat germ lectin and concanavalin A.

The specificity is inherited in a simple Mendelian manner and the gene controlling its synthesis is allelic to the one controlling the synthesis of the McAl antigen.

A series of derepressed mutants of the tetracycline resistance (T) determinant in R-factor R57 have been found to be repressor-negative and recessive to the T determinant in R6. It is shown that these (Tdr) mutants are dominant to the inducible T determinant in RPl, indicating that the T determinants in R57 and RP1 code for different repressors of the resistance gene. The same Tdr determinants are unstable in cells carrying both the R57 mutant and RP1, probably due to selection against the dominant Tdr gene because it depresses the growth rate of the host cell compared with its T+ homologue. It is suggested that the T determinants giving high-level resistance in R57, R6 and R100 form one homologous group, probably disseminated by the transposon TnlO, while T determinants giving a much lower level of resistance, such as that in RP1, form a separate group, which may include those in R46, and R199. It is proposed that the gene responsible for tetracycline resistance should be designated tetA and the repressor gene tetI. The R57 Tdr mutants then have the genotype tetI−tetA+.

The number of blastoderm cells in Drosophila whose descendants form adult structures has frequently been estimated from genetic mosaics. Data from somatic recombination (method I) and gynandromorph (method II) mosaics both yield very low estimates, e.g. about 10–20 progenitor cells for the eye and antenna, wing or leg.

In gynandromorphs the mosaic dividing line has a random orientation on the blastoderm. In the 6000 cell blastoderm it should be very unlikely that the mosaic dividing line passes through any small patch of only 10–20 cells. Yet it has been reported that 10–25% of eye/antenna, wing or leg disks in gynandromorphs are mosaic. Thus the frequency of mosaicism data seems to be in contradiction to the progenitor population estimates. Similar discrepancies are found in the data for other adult structures.

In this paper we derive a formula for estimating the number of cells in a blastoderm patch from the frequency with which the gynandromorph dividing line passes through it (method III). In a second method (method IV) we use the maximum distances inside the progenitor areas on a fate map to estimate the progenitor patch size. These two estimates agree closely with each other. We find, e.g. that 50–100 cells are in the patches from which the eye/antenna, wing or leg disks derive.

We examine a number of possible explanations for why the first two estimates are so much smaller than the last two. The former estimates refer to the number of progenitor cells which actually have descendants in the adult structure; the latter estimates refer to the total patch area in which the progenitor cells sit. With the present information the most reasonable conclusion is that the progenitor cells for the adult structures are dispersed among other cells which have different developmental fates. If confirmed by experiment, this result has many implications for the process of determination.

Adult females from 19 strains of mice were injected with either coumarin or 7-ethoxycoumarin and the urinary excretion of the umbelliferone produced by the metabolism of these substances was measured. With the exception of C57L the strains fell into three classes as follows: high metabolizers (DBA/1 and DBA/2), medium metabolizers (CBA, 129/Rr, NZB and NZW) and low metabolizers (the other 12 strains). The difference in metabolizing ability between the medium group and the low group of strains was also evident when the 4-methyl derivatives of the same two substances were used. However with the 4-methyl derivatives there was no difference in metabolizing ability between the medium group and the high group. The results are interpreted as evidence that the gene Coh on chromosome 7 comprises two closely linked genes which determine cytochrome P-450 isozymes with different substrate specificities.