Plasmodial formation in the Myxomycete Physarum polycephalum is controlled by a mating type (mt) locus. There are a number of different heterothallic mt alleles; and also a variant, mth, that allows plasmodial formation in pure clones. This paper reports an analysis of this differentiation system. The strain CL (mth) forms plasmodia in pure clones (i.e. it selfs). CL was mutagenized with NMG and 21 mutants unable to differentiate into amoebae were isolated. The mutants, together with CLd, fell into two complementation groups, twelve in difA and ten in difB. Both complementation groups are closely linked or allelic to the mt locus. difA represents a gene essential for plasmoclial formation, but it is suggested that difB represents a class of revertants to the mt2 heterothallic state. A model of the control of plasmodial formation is proposed in which the mt locus is suggested to code for the repressor of the difA gene. Genetic control is explained in terms of the dilution of allele-specific repressors.

Plasmodial formation in the myxomycete Physarum polycephalum is controlled by a mating type (mt) locus, with heterothallic amoebae normally being unable to form plasmodia in pure clones. We report the isolation by mutagenesis of selfing mutants from heterothallic strains, and their analysis. Various amoebal strains of different mating types were mutagenized with a range of mutagens, and a number of selfing mutants (designated Het−) were isolated. A specific sensitivity of mt2 amoebae to mutagenesis by NMG was observed. This sensitivity segregated as a single locus closely linked or allelic to the mt2 locus. When the Het− clones were incubated at 30 °C, selfing was greatly inhibited. This property was used to determine the mt specificities of four Het− clones. The process of plasmodial induction in pure clones of CL was also studied using the 30 °C temperature effect.

Plasmodial formation in the Myxomycete Physarum polycephalum is under heterothallic control by a mating type (mt) locus. In natural isolates only amoebae with different mt alleles are able to cross to form diploid plasmodia. A class of mutants isolated from heterothallic amoebae, together with the variant strain CL, is able to form plasmodia in pure clones, designated as selfing. Non-selfing mutants have been isolated from CL and from other selfing amoebae.

This paper reports the isolation and analysis of 64 non-selfing derivatives (designated Npf−) from seven selfing (Het−) strains. The Npf− mutants could be grouped into eight classes on the basis of their crossing and complementation patterns. The possible significance of these mutants is discussed.

1. The occurrence of fusion between plasmodia produced from amoebal clones of P. polycephalum was studied.

2. The occurrence of fusion was found to be strain-dependent and the factors responsible segregated in the progeny of a cross.

3. The segregations found in crosses between several strains led to the conclusion that four alleles (f1–f4) of one gene f were controlling fusion in these strains.

4. Fusion occurs only between plasmodia carrying identical f alleles, except in one class of results.

5. A model accommodating all the results, including the ‘exceptional’ class, is proposed. It requires that the action of the f factors is to inhibit fusion between dissimilar strains rather than to promote fusion between identical strains. Certain physiological deductions from this model are discussed.

6. The locus (mt) determining mating type of the amoebae is not concerned in plasmodial fusion and is unlinked to f.

7. The rate of fusion between some pairs of strains is apparently influenced by modifying genes.

8. It is suggested that, as a result of the operation of the f gene and of the previously described killing reaction, heterokaryons will occur rarely in natural populations of P. polycephalum.

The homothallic amoebal clones of Physarum polycephalum are of potential use in understanding the developmental genetics of this organism. Such an application requires that complementation and recombination analysis be possible between pairs of homothallic clones. This paper is a report of the formation of mixed plasmodia by pairs of homothallic amoebal clones. In order to detect such mixed plasmodia use was made of two marker genes involved in plasmodial fusion, fusA and fusB. Sporulation of a mixed plasmodium formed from two homothallic (delayed) amoebal clones yielded progeny amoebae which were genetically recombinant. It is deduced from the ratios of various genotypes in these progeny clones that the mixed plasmodium was diploid and that meiosis was associated with sporulation. There is therefore no impediment to the use of the homothallic strains for genetical analysis. The progeny amoebal clones were observed to be showing segregation for the characters homothallic (rapid) and homothallic (delayed). This observation, taken together with other related observations, suggests that the homothallic (delayed) character is produced by mutation of the homothallic (rapid) character. The rare plasmodia formed by a homothallic (delayed) amoebal clone are the result of reversion of this mutation. Amoebal clones of the homothallic (delayed) type are therefore developmental mutants unable to perform the differentiation from amoeba to plasmodium.

A genetic polymorphism is responsible for determining that some humans express lactase at high levels throughout their lives and are thus lactose tolerant, while others lose lactase expression during childhood and are lactose intolerant. We have previously shown that this polymorphism is controlled by an element or elements which act in cis to the lactase gene. We have also reported that 7 polymorphisms in the lactase gene are highly associated and lead to only 3 common haplotypes (A, B and C) in individuals of European extraction. Here we report the frequencies of these polymorphisms in Caucasians from north and south Europe and also from the Indian sub-continent, and show that the alleles differ in frequency, the B and C haplotypes being much more common in southern Europe and India. Allelic association studies with lactase persistence and non-persistence phenotypes show suggestive evidence of association of lactase persistence with certain alleles. This association was rather more clear in the analysis of small families, where haplotypes could be determined. Furthermore haplotype and RNA transcript analysis of 11 unrelated lactase persistent individuals shows that the persistence (highly expressed) allele is almost always on the A haplotype background. Non-persistence is found on a variety of haplotypes including A. Thus it appears that lactase persistence arose more recently than the DNA marker polymorphisms used here to define the main Caucasian haplotypes, possibly as a single mutation on the A haplotype background. The high frequency of the A haplotype in northern Europeans is consistent with the high frequency of lactase persistence.

A susceptibility locus for schizophrenia in the ‘pseudo-autosomal’ region has been proposed on the basis of the reported excess of sex-chromosome aneuploidies (e.g. XXY and XXX) among patients with schizophrenia and the finding that schizophrenic sib-pairs are more often of the same than of the opposite sex. This hypothesis has been tested in 83 sibships with two or more siblings fulfilling Research Diagnostic Criteria for schizophrenia or schizoaffective disorder. Alleles at the pseudo-autosomal telomeric locus DXYS14, which is unlinked with sex, were analysed using the method of affected sib-pairs. Affected sibs shared alleles at DXYS14 more frequently than expected by random Mendelian assortment, supporting genetic linkage between DXYS14 and schizophrenia.

The activities of the A and B forms of the enzyme monoamine oxidase (MAO, E.C. 1.4.3.4) have been assessed with the substrates 5-hydroxytryptamine and benzylamine respectively in seven areas of the brains of 39 patients with schizophrenia and 44 control subjects. Whereas previous studies have found the enzyme unchanged in brain in schizophrenia, in this study there was a modest but significant decrease in the activity of MAO-B in frontal and temporal cortices and in amygdala. This decrease could not be accounted for by neuroleptic medication, age, sex or post-mortem variables. In a series of 22 patients who had been assessed in life, the reduction in MAO-B activity was found to be associated specifically with the presence of negative symptoms (flattening of affect and paucity of speech). The findings are therefore consistent with other evidence for structural and neurochemical change in the temporal lobe that have been associated with the type II (defect state) syndrome of schizophrenia. The change in enzyme activity is unlikely to be related to a change in monoamine metabolism but may reflect a disturbance in glial function. The change in MAO-B activity in brain in this study is confined to particular areas of brain and a subgroup of patients; it is thought to be entirely unrelated to earlier reports of reductions of enzyme activity in platelets, which are probably attributable to prolonged neuroleptic medication.

Opioid receptor binding sites were assessed in membrane preparations of caudate nucleus from post-mortem brains of controls and of patients with schizophrenia. There was no difference between the two groups in the total specific binding of 3H-etorphine or in its ‘μ’ and (‘δ+χ’) components. Similarly, the binding of 3H-naloxone did not differ between patients and controls. It is concluded that a previous report of reduced opioid receptors in caudate of schizophrenics is unlikely to prove a consistent finding and that the results of the present study offer no support to the claim that there is a general disturbance in opiate mechanisms in schizophrenia.