Showing papers in "Genetics in 1969"

The number of heterozygous nucleotide sites maintained in a finite population due to steady flux of mutations.

Abstract: N natural populations, it is expected that there is a constant supply of mutaI tions in each generation. These mutations may have different persistence depending on their fitnesses, but collectively, they constitute the ultimate source of genetic variability in the populations. Since the maintenance of genetic variability is an important subject of study in population genetics, it may be worthwhile to investigate, using various models, the effect of mutation on the genetic variability. For example, KIMURA and CROW (1964) studied the number of alleles maintained in a finite population, assuming that each mutant is an allele not preexisting in the population. In the present paper I will use a different model and will investigate the number of heterozygous sites per individual and some related quantities that represent the statistical properties of the mutant frequency distribution, assuming that a very large number of independent sites are available for mutation. In this paper, “site” refers to a single nucleotide pair, although the theory is still appropriate to a small group of nucleotides, such as a codon.

The behavior of four neurological mutants of Drosophila.

Abstract: INGLE gene changes offer an efficient and attractive way to study the genetic control of behavior. Drosophila, with its numerous technical advantages, would seem to provide a fruitful approach in working out the complexities of neurological control. The four neurological mutants discovered serendipitously and described in this report present just such an opportunity. The phenotype common to all four is a rapid shaking of the legs following etherization. Because the mutants appeared, among the progeny of four different males of the original thirty treated, they represent four independent mutational events. Subsequent study has disclosed that three separate gene loci are involved, all on the X-chromosome. This shaking phenotype has been described previously in D. melanogaster by CATSCH (1944) who localized the dominant gene at 58 on the X-chromosome and named the mutant, Shaker, because of its resemblance to the sex-linked dominant in D. funebris (LUERS 1936). Since then three other occurrences of the Shaker phenotype in D. melanogaster have been reported, ( NOVITSKI 1949; FAHMY and FAHMY 1959) all produced by a gene change at the original Shaker locus. To our knowledge, however, these stocks no longer exist nor were the studies carried beyond the description of the phenotype and the localization of the gene.

A mutational analysis of conidial development in Aspergillus nidulans.

Abstract: NDIVIDUAL morphological mutants have been studied in many higher organ' isms such as Drosophila (HADORN 1955) and the mouse (GRUNEBERG 1952), but a rigorous mutational analysis of the type employed on many biochemical pathways is readily carried out only in microorganisms. The most remarkable study of this type is the work on bacteriophage T4 (EPSTEIN et al. 1963) in which the whole of the development of the virus is open to analysis. In more complex organisms the spectrum of morphological mutants obtainable is very broad (e.g., in Neurospora: GARNJOBST and TATUM 1967) and analysis can only be carried to any depth if attention is confined to a process such as sporulation (reviewed in HALVORSON, VARY and STEINBERG 1966). or to mutants affecting an individual enzyme (e.g., BRODY and TATUM 1966). Aspergillus nidulans, unlike most eukaryotes, lends itself to a similar approach since it can be treated as a microorganism and has a well-studied genetic system (PONTECORVO et al. 1953). The conidial apparatus is a particularly suitable subject, as the structure is a well-defined one, and the spores possess a distinctive green pigment so that mutants lacking this can readily be picked up and examined for modification or absence of conidia. Most important, however, is the fact that the conidia are dispensable structures, inessential for normal growth, and indeed, inessential for storage and propagation since the sexual cycle in this homothallic organism provides an alternative source of spores. The structure of the conidial apparatus of Aspergillus nidulans is shown in Figures 1 and 2. Like the hyphae, the conidiophores and vesicles are multinucleate, but the sterigmata and conidia are uninucleate (PONTECORVO et al. 1953; CLUTTERBUCK 1969). Initiation of conidiation in ascomycetes is complex (MORTON 1961 ; TURIAN 1966), and preliminary studies in A. nidulans suggest that there is a balance between conidiation and production of cleistothecia or aerial mycelia. Considering this complexity, it was decided to accept for study only those mutants that had a normal density of conidiophore initials; that is, to confine the study to the processes following conidiophore initiation. A second limitation imposed on this analysis is the rejection of mutants whose linear growth rate on agar is less than that of the wild type. This is done in order to exclude the many mutants in which there is a defect in their normal metabolism that only has a serious effect during conidiation. Since the subject of this

Protein polymorphism and genic heterozygosity in a wild population of the house mouse (Mus musculus).

Abstract: PROTEIN polymorphisms demonstrable by zone electrophoresis are finding increasing use in studies of the population genetics, systematics, and ecology of rodents. For wild populations of the house mouse (Mus musculus), studies to date have dealt largely with esterases and hemoglobin (PETRAS 1967; SELANDER and YANG 1969; SELANDER, YANG and HUNT 1969), although genetically determined variation in a variety of other proteins has been described in laboratory strains and may be expected to occur in wild mice from which the domestic forms were derived. In an effort to increase the number of protein types available for studies of wild populations, and to assess the extent of genic polymorphism in wild populations of this species for comparison with estimates available for Drosophila and other organisms, we have examined electrophoretic variation in 35 enzymes and nonenzymatic proteins in samples of mice taken in several barns at a farm in southern California.

Linkage disequilibrium at steady state determined by random genetic drift and recurrent mutation.

Abstract: order to understand the genetic architecture of Mendelian populations, we '2ave to know, in addition to gene frequencies, the degree of linkage disequilibrium between loci, namely, the extent to which combinations of genes at linked loci deviate from randomness. In panmictic populations, two factors are mainly responsible for the production of linkage disequilibrium. They are epistatic interaction in fitness and random sampling of gametes in reproduction. Although a number of papers have been published since the work of KIMURA (1956), treating the problem of epistasis and linkage in an infinite population, it was only last year that the first systematic treatment of linkage disequilibrium due to random drift was presented by HILL and ROBERTSON (1968). Using the method of moment-generating matrix, they obtained the variance of the linkage disequilibrium coefficient as a function of time and initial gametic frequencies for the case of no recombination, assuming that mutation and selection are absent. In addition, they studied numerically several cases of recombination by multiplying the moment-generating matrix and also by carrying out simulation experiments. They demonstrated that significant linkage disequilibrium may result from random drift under tight linkage and small population number. Their results were extended by OHTA and KIMURA (1969) who obtained, by the method of Kolmogorov backward equation, the formula for the variance of linkage disequilibrium in which recombination is incorporated. In natural populations, however, it is expected that random drift and recurrent mutation balance each other so that a steady state is reached with respect to linkage disequilibrium. SVED (1968) studied this problem assuming that all gene frequencies are held at 50% by strong overdominance while mutation is so rare as to be negligible. Presumably, his treatment is applicable to a certain transient state but not necessarily to the equilibrium state. In the present paper we intend to present a theoretical foundation for the treatment of linkage disequilibrium at steady state determined by random drift and mutation (or more generally, linear evolutionary pressure). The problem of linkage disequilibrium will become particularly important when we consider two neighboring nucleotide sites within a cistron for which the recombination fraction may be much smaller than the reciprocal of the population number. It will also

The galactose operon of E. coli K-12. II. A deletion analysis of operon structure and polarity.

Abstract: PREVIOUS genetic studies have conclusively established the order of the three structural genes in the galactose operon to be epimerase-transferasekinase (see Figure 1 ) ( ADLER and KAISER 1963; BUTTIN 1963b; ADLER and TEMPLETON 1963). The elegant work of ADLER and TEMPLETON (1963) and subsequently of KAYAJANIAN (1965), DAVISON, FRAME and BISHOP (1967), and PFEIFFER and OELLERMAN ( 1967) have demonstrated the feasibility of high-resolution deletion mapping of the kinase and transferase structural genes by the use of xdg transducing particles which carry partial galactose operons. However, because only transducing particles carrying an intact, active epimerase gene can be isolated and purified, they cannot be used to map the epimerase end of the operon. Both biochemical (MICHAELIS and STARLINGER 1968) and genetic (ADHYA and SHAPIRO 1969) data suggest that reading of the galactose operon proceeds from the epimerase end and that there exist one or more non-structural, regulatory elements in which mutations can lead to reduction or abolition of the activity of all three genes of the galactose operon. Hence, the need for a complete and detailed map of the galactose operon, in particular the epimerase gene, is clear. In this communication we shall present such a map based on the use of transducing phage and bacterial deletions. Our results confirm our previous conclusion on the epimerase to kinase polarity of the galactose operon and show that essential and ratelimiting regulatory elements are located at the epimerase end.

Linkage modification and sex difference in recombination

Abstract: IN a previous paper entitled “Modification of linkage intensity by natural selection,” NEI (1967) showed that linkage intensity may be modified either through structural changes of chromosomes or through selection of modifier genes affecting recombination frequencies, provided that there is gene interaction or epistasis between the loci whose recombination value is to be modified. In the study of selection of modifier genes, it was assumed that the modifier genes are inherited independently of the genes between which recombination is to be modified in both haploid and diploid populations. Most viruses and bacteria, however, appear to have only one chromosome, so that all genes are necessarily linked, although a pair of genes located far apart may be inherited almost independently. Even in higher organisms, those genes located near the modifier genes are not inherited independently of the latter. It is, therefore, desirable to consider the modification of linkage intensity with a linked modifier gene. In some organisms, recombination values differ between the two sexes. For example, male Drosophila melanogaster show no intrachromosomal recombination, while such recombinations do occur in females. It seems that wherever crossing over is absent or markedly reduced in one sex, that sex is the heterogametic sex, as indicated by HALDANE ( 1922) and HUXLEY (1 928), though there are several exceptions (DUNN and BENNETT 1967). In the present paper we will consider the modification of linkage intensity between genes on the autosomes as well as on the sex chromosomes, assuming an arbitrary degree of linkage between the modifier gene and two genes whose recombination frequency is to be modified. In this paper emphasis will be on the efficiency of linkage modification by a linked modifier rather than on the relationship between linkage modification and genotype fitnesses, since this relationship has been dealt with in the previous paper. LINKAGE MODIFICATION WITH A LINKED MODIFIER

Molecular characterization of the Drosophila genome.

Abstract: A remarkable feature of evolution in the genus Drosophila is the conservation of the basic karyotype. Postulation of Robertsonian centric fusions (ROBERTSON 1916) is sufficient to explain most of the karyotypic rearrangements found in the various species. The fixation of large duplications of genetic material during the evolution of this genus appears to have been rare (STONE 1955). On the other hand, amino acid sequence data for proteins of other organisms indicate that many cistrons have very similar nucleotide sequences, and are presumably related by prior gene duplication (JUKES 1966). Physical studies of DNA of various eucaryotes also suggest that these genomes contain very large families of related cistrons (BRITTEN and KOHNE 1968). The size of such families is often in excess of that inferred from existing protein data (BRITTEN and KOHNE 1968; MCCARTHY 1967; WETMUR and DAVIDSON 1968). This may in some cases reflect the presence of cistrons with similar nucleotide sequences which specify proteins of overtly different functions. It is also likely that some of these families of genes have functions other than the determination of amino acid sequences. In keeping with the cytological studies, the reassociation kinetics of denatured Drosophila melanogaster DNA imply that the genome of this organism is much less complex, in terms of intragenome nucleotide sequence homologies, than those of vertebrates (LAIRD and MCCARTHY 1968b). Estimates made from these measurements suggest that perhaps 90% of D. melanogaster nucleotide sequences are not closely related to others elsewhere in the genome. In light of the extensive diversity within the genus Drosophila (LAIRD and MCCARTHY 1968a) , a detailed analysis of the intragenome homologies of representative species is expected to provide information about the evolution of genomes. In particular, our results indicate that genome simplicity extends to other Drosophila species and to a representative of another Dipteran family. In addition, there are variations among Diptera in genome size as inferred from the informational content of nucleotide sequences. MATERIALS AND METHODS Details of labeling and isolation of DNA and RNA from Drosophila, preparation of filterbound DNA, hybridization and duplex formation procedures, and analytical CsCl pycnography

The estimation of fitnesses from population data.

Abstract: HIS paper is concerned with certain statistical problems which arise in conTnection with attempts to estimate fitnesses from the genotype frequency data produced by artificial populations in which rapid changes in genotype frequencies are taking place. The special situation of concern here is the one in which the investigator wishes to obtain several estimates of fitness, each taken from small segments of the selection curve, in an attempt to evaluate patterns of change in fitness as the experiment proceeds. Examples of such attempts are DOBZHANSKY and LEVENE (1951), POLIVANOV (1964), TOBARI and KOJIMA (1967) and YARBROUGH and KOJIMA (1967). The problems of estimation arise when the genotypes are classified and counted in each generation at a stage when the selection process is incomplete. PROUT (1965) pointed out that if selection is incomplete at the time of observation, then estimates of net fitness could not be obtained by methods then in use. The present paper constitutes an extension of this analysis.

Conjugation in Pseudomonas aeruginosa.

Abstract: N general terms, the characteristics of the conjugation system in Pseudomonas I aeruginosa show some similarities to those of the more intensively studied Escherichia coli. Mating occurs between parents differing in the possession of a fertility factor FP. Genetic transfer is from the male FP+ or donor parent to the female F P or recipient parent. The sex factor FP is infectious in that it can be transferred from some FP+ strains to the FPstrain 1 at a frequency far in excess of that found for the transfer and recovery of chromosomal markers. Not all FP+ strains are infectious and as male forms comparable to the E. coli Hfr have not yet been found, the role of FP in transferring chromosom? is uncertain. Two main issues have conditioned our approach in this further study of pseudomonad conjugation. Firstly the nature of chromosome transfer in P. aeruginosa, and secondly the use of conjugation for the general mapping of the P. aeruginoaa chromosome. In selecting the experimental system to do this, it became obvious that there were distinct advantages in carrying out matings between F P and FP+ forms of the same strain as has been done with E. coli K12. Recombination in P. aeruginosa was first demonstrated between four unrelated strains (HOLLOWAY 1955). However, we have since shown that in the best studied of these mating combinations, 1 . P x 2.FP+, the recombination of markers is considerably influenced by DNA host-specificity differences ( HOLLOWAY and ROLFE 1964; ROLFE and HOLLOWAY 1966). As FP from strain 2 can be introduced into strain 1 by recombinants from 1 X 2 crosses which are infectious for FP (HOLLOWAY and JENNINGS 1958), such differences can be avoided by using 1 . F P x 1 .FP+ crosses. Previously, mating in P . aeruginosa was carried out by plating washed saline suspensions of the two parents onto minimal agar. The analysis of recombinants derived from such a procedure can be used to determine some aspects of linkage but such results do not enable us to draw any conclusions as to how chromosome is transferred. In this paper we will describe the application of an interrupted mating technique to P. aeruginosa to show that there is an oriented transfer of chromosome; and to discuss the use of this technique for linkage studies.