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Wright's model for the effects of random fluctuations in gene frequency in a population of fixed size is generalized to randomly fluctuating population size, and treated from the viewpoint of G. Malécot, using a martingale convergence theorem. The gene frequency approaches a limit, whose value depends on the actual realization, or history, of the process; that is, convergence is with probability one (or: almost surely) in statistical language. The limit does not necessarily represent a state of fixation of either allele; in particular, the limiting probability distribution is not necessarily trivial. For the special case of deterministically varying population size, a necessary and sufficient condition for such non-triviality is given.

The degree of misreading in vitro as a function of increasing concentrations of streptomycin was determined for ribosomes of three Escherichia coli mutants resistant to streptomycin and of the parental strain. By comparison with mutants of known allele types it was found that mutant SM-1 belongs to allele type A40, SM-5 to type A60 and SM-10 to type A1. Ribosomes were isolated from 2–3 kg cells of each of the mutants and the parental strain. After separation of subunits in zonal rotors and extraction of proteins from 30-S subunits the ribosomal proteins were separated by CM-cellulose chromatography and Sephadex gel filtration. Protein S12, which is altered in streptomycin mutants, was digested with trypsin and the tryptic peptides were analysed after separation by SE-cellulose and paper chromatography. Comparison of the amino acid compositions of all peptides from the mutants with those of the parental strain and sequence analysis of the altered peptides revealed the following amino acid replacements: Lysine by arginine in peptide T15 (position number 87 of protein S12) in mutant SM-1, lysine by arginine in peptide T6 (position 42) in SM-5 and lysine by asparagine in peptide T6 (position 42) in SM-10. There is good agreement between our protein-chemical results and previous genetic data on streptomycin-resistant mutants as discussed in the last section of this paper.

We have found that the phenol oxidase activity in 50-hr Drosophila melanogaster pupae is much greater than that of adult flies. The mutants lz and lzg have all of the phenol oxidase components present in wild type, whereas the mutant tyr-1 has all of the wild-type components but the activity of each component is greatly reduced in comparison with wild-type activity. The newly discovered lozenge allele, lzrfg, lacks all phenol oxidase activity.

Neurospora crassa can utilize glucose 6-sulfate as its sole sulfur source, although this compound cannot serve as a carbon source for this organism. Neurospora possesses a transport system capable of glucose 6-sulfate uptake; the system is energy dependent, is inhibited by extracellular sulfate, and is clearly distinct from the permeases responsible for the uptake of glucose and those for sulfate transport. The metabolism of glucose 6-sulfate apparently involves its transport as an intact molecule, followed by a slow intracellular hydrolysis. Methionine, which represses the synthesis of a number of enzymes of sulfur anabolism, also represses the synthesis of the transport system responsible for glucose 6-sulfate uptake. A regulatory gene, cys-3, which controls the synthesis of aryl sulfatase, choline sulfatase, choline-O-sulfate permease, and two distinct permease species, also regulates the permease for glucose 6-sulfate.

The oxidation of both N1-methylnicotinamide and pyridoxal appears to be catalyzed by a single liver enzyme, aldehyde oxidase (aldehyde:oxygen oxidoreductase, EC 1.2.3.1). This notion is based on the following evidence: (1) Inbred strains of mice having characteristic and different levels of N1-methylnicotinamide oxidase activity also differ in their abilities to oxidize pyridoxal; the levels of the two activities have been found to vary among the strains in a parallel fashion. (2) The Km values of the N1-methylnicotinamide oxidizing activity for N1-methylnicotinamide and pyridoxal oxidizing activity for pyridoxal also vary among the inbred strains of mice in a parallel fashion. (3) The genetic determinants of pyridoxal and N1-methylnicotinamide oxidizing activity in the mouse do not segregate in the F2 generation or in backcrosses to the parental strains. (4) The levels of N1-methylnicotinamide and pyridoxal oxidizing activities in male mice increase in a parallel fashion upon the attainment of sexual maturity. (5) Competition of N1-methylnicotinamide and pyridoxal for oxidation in vivo has been demonstrated in the rat. (6) The inactivation of N1-methylnicotinamide oxidase activity which is connected with catalytic performance results in an equal loss of pyridoxal oxidase activity. A parallel loss in activity for both substrates also results from the catalysis of pyridoxal oxidation. In the course of these studies, a genetic analysis of aldehyde oxidase in the C58/J and C57B1/6J strains of mice was conducted. The earlier conclusion that aldehyde oxidase is controlled by a single autosomal locus with alleles acting in a codominant manner has been confirmed.

From a consideration of genetic and chromosomal alterations which affect the banding pattern of a specific salivary chromosome region, it is concluded that (1) a regulator locus, sal, is closely linked with the region in question but separated from it spatially by a few bands; (2) either mutation of the sal locus or transfer of the region to a heterochromatic region affects the banding pattern similarly; and (3) the change probably consists of a compaction of DNA and a concomitant inactivation of genetic loci.

A microscale isoelectric focusing technique has been developed and used to study hypoxanthine-guanine phosphoribosyl transferase (HGPRT; E.C. 2.4.2.8, inosinate-guanylate:pyrophosphate phosphoribosyl transferase) activities in mouse and human cell lines. The enzymes of both mouse and human origin are shown to exhibit considerable heterogeneity, but each type has a unique range of isoelectric pH. The enzyme of a mouse × human hybrid cell line, derived by fusion of HGPRT− parental cells, gives a homogeneous peak of activity, unlike the wild-type enzyme of either parent. The possibility is suggested that this enzyme activity is due to intra-allelic complementation.

Wild-type alleles at the peak locus of Neurospora have been transferred by backcrossing from N. sitophila and N. tetrasperma to N. crassa. In the genomic background of N. crassa the different wild-type alleles show strikingly different dominance relations with Pk-4, a dominant peak mutation in N. crassa.

Tetrazolium oxidase from the blood and liver of rainbow trout was found to be genetically polymorphic. The inheritance pattern of the liver enzyme was compatible only with a one locus-two allele hypothesis. The enzymes in the blood while having an electrophoretically identical polymorphism could differ genotypically from that of the liver in a given fish. The significance of these findings to the understanding of the evolution of the salmonid genome is discussed.

Two electrophoretic forms of erythrocytic carbonic anhydrase were found to be controlled by one autosomal locus with two codominant alleles, CAf and CA8. The gene frequencies for the CAf and CA8 alleles were found to be.15 and.85, respectively, in a sample of 53 mice from Middlesex County, New Jersey. The observed genotypic frequencies indicated that the population was in Hardy-Weinberg equilibrium.

The soluble sulfur pool of wild-type Neurospora was examined in extracts from mycelia, conidia, and ascospores. The soluble sulfur pools of the regulatory mutants cys -3 and scon c , and of several cysteineless mutants, were also studied. While the sulfur pool of mycelia is complex, the conidial sulfur pool contains only a few specialized components, including choline- O -sulfate and cysteine. A third component of the conidial pool, also found in mycelia has been shown to contain adenine, guanine, ribose, phosphate, cysteine, and homocysteine. Cys -3 and the other cysteine-less mutants, which are unable to utilize exogenous choline- O -sulfate, were found to contain normal levels of this compound in their conidia. The sulfur pool in conidia of scon c was characterized by normal proportions of each of the components, but the size of the total sulfur pool was significantly altered in this strain. Ascospores were found to contain only choline- O -sulfate (80%) and cysteine (20%) in their soluble sulfur pool, but the presence of some insoluble sulfur storage compound was suggested by an increase in the total size of the soluble sulfur pool observed during spore germination.

In a survey of mice from 40 inbred strains, largely previously untested, four alleles were distinguished at the Hba locus, determining structure of adult mouse hemoglobin α chain. This finding supports and extends previous sequence studies by others. Methods are given by which each phenotype was characterized by its solubility profile at varying pH and by its chromatography pattern. Concordance was complete between histidine-positive αT-4 (defining Hbac) and high-intermediate solubility profile. In three inbred strains, a distinct new low-solubility profile, not associated with his-positive αT-4, was recognized, and mice with this phenotype were classified as Hbad. Implications of observed widely distributed four-allele polymorphism of mouse hemoglobin α-chain structure are discussed.

Evidence of strong association of alleles at the Esterase-5 and adult Acid phosphatase-6 loci with the Sex Ratio and the Standard X chromosome arrangements in D. pseudoobscura is presented. There is no differentiation at these two loci, either in the Sex Ratio or the Standard arrangement from two widely separated geographic populations. At the Esterase-5 locus, alleles characteristic of one arrangement are found in low frequencies in the other arrangement. It is concluded, from these and other observations that the differentiation between the Sex Ratio and the Standard arrangement, at these two loci, is a result of natural selection favoring different coadapted gene blocks in these arrangements. The average heterozygosity at these two loci in different karyotypes is in the following order: ST/SR > ST/ST >> SR/SR which agrees very well with the fitness estimates of these karyotypes.

A 49-year-old woman, suffering from peripheral vascular disease, was found to have two lipoprotein abnormalities, namely, type III hyperlipoproteinaemia and sinking prebeta lipoprotein. Twenty-one members of the kindred were investigated in an attempt to determine the pattern of inheritance of both of these abnormalities. In a 21-year-old son of the proband plasma electrophoresis was in keeping with a type V hyperlipoproteinaemia. It is suggested that this may be a stage in the development of the characteristic type III pattern. If this is so it is consistent with previous suggestions of an incompletely penetrant single autosomal allele. Sinking prebeta lipoprotein was found in the plasma of two other members of the family. If this abnormality is also inherited as a single autosomal allele it must have a very low penetrance and the possibility that the abnormality is acquired cannot be excluded.

L'analyse des acides amines de la cystinurie du type I-III dans l'urine de deux enfants d'un heterozygote double a revele que les quantite d'acides amines dibasiques excretees en 24 h sont celles qui furent trouvees chez les heterozygotes de la cystinurie du type III. Les donnees experimentales s'accordent sur ce point que les types biochimiquement heterogenes de la cystinurie sont regies par des alleles.

ANALYSES of eye-colour mutants have brought important contributions to the genetics, as well as to the biochemistry, of pigment metabolism of insects1. As in Drosophila, Ephestia and Bombyx, mutants have been found in Apis mellifera which are more or less different in their eye colour2,3. Although several genetic studies have been carried out on these honey bee mutations3,4, their characteristic phenotypes have not been analysed chemically. The objective of the research reported here was to identify the substances producing the eye colour of the mutants and to follow every change in their metabolism so that all mutants could be chemically characterized.

The previous paper (LANGLEYT,O BARanId KOJIMA 1974) reports that the directional linkage disequilibria, Dw = PABPab-PAbPaB, tend to be negative for data between allozymes and linked to inversions. A and B stand for the two alleles with the greatest frequency in the population. In this paper we show that linkage disequilibrium in this direction is produced at equilibrium when double homozygotes have fitnesses that are a constant fraction of the product of the two component single homozygote fitnesses, a pattern that is frequently observed in experimental data.

In this paper a beginning is made on the sampling theory of neutral alleles. That is, we consider deductive and subsequently inductive questions relating to a sample of genes from a selectively neutral locus. The inductions concern estimation, confidence intervals and hypothesis testing. In particular the test of the hypothesis that the alleles being sampled are indeed selectively neutral will be considered. In view of the large amount of data currently being obtained by electrophoretic methods on allele frequencies and numbers, and the current interest in the possibility of extensive “non-Darwinian” evolution, such a sampling theory seems necessary. However, a large number of unsolved problems in this area remain, a partial listing being given towards the end of this paper.

Summary. Results of typing platelet specimens from 299 random group 0 blood donors with three antibodies agree with the hypothesis that the antigens detected are controlled by three alleles present in Caucasian populations with frequencies of 0.276,0.109,0.179. These alleles are denoted by PIB1, PIB2 and PIB3 respectively. The remaining 43.6% of alleles at this locus PIB- are not detectable with antibodies discussed in this paper. Tests on twelve families with a total of 34 children support this hypothesis. Evidence is presented from population data supporting the hypothesis that PIB1 and PIB3 are identical or closely related to LA2 and LA1 respectively. Population data also supports the hypothesis that PIB2 and PIB3 correspond to 7d and 7c respectively. In the appendix of this paper a description is given of a statistical technique that demonstrates the number of specimens from a population that should be typed in order to distinguish between the hypotheses of allelism and independence of genes controlling blood group antigens.

The recessive lethal amber suppressor su + 7(UAG-1) in Escherichia coli inserts glutamine in response to the UAG codon. The genetic analysis presented in this paper shows that the su − 7 precursor allele can give rise to suppressors of the UGA codon as well as of the UAG codon. This observation suggests that the su − 7 gene normally codes for transfer RNA Trp , a tRNA whose anticodon can be modified by single base changes to forms that can translate either UAG or UGA. The chemical findings presented in the accompanying paper (Yaniv et al. , 1974) are wholly in accord with this interpretation. Thus, a single base substitution in the anticodon sequence of a tRNA can affect both the coding specificity of the molecule and also the amino acid acceptor specificity.

This paper gives a development of ideas presented in a previous paper on the dynamics of haploid genetic populations in an infinite habitat. A brief review of necessary ideas and a discussion of a concept of value for haploid populations are given. A general model for a diploid population, which incorporates life tables, mating of individuals, and fecundities is presented and general recursive relationships for frequencies of genetic types developed. Because of its intractability special cases are then considered in which there is equal fecundity of all matings in the population of matings that occurs. It is found that in some cases the numbers of the various types increase asymptotically at geometric rates, so that each type may be said to have a Malthusian parameter. It is then found that a version of Fisher's Fundamental Theorem holds in that the asymptotic rate of increase of the average Malthusian parameter is equal to the genotypic variance in this parameter. Additionally, the Malthusian parameters are found to be additive. It does not seem possible, however, to extend the concept of value to diploid mating populations.