Showing papers in "Genetics in 1967"

Linkage and selection: theoretical analysis of the deterministic two locus random mating model.

Abstract: Introduction. 1. The general model. 2. The condition for the existence of a nontrivial equilibrium with D = 0. 3. The additive viability model. 4. The multiplicative viability model. 5. A general necessary condition for the stability of a nontrivial equilibrium with D = 0. 6. A general symmetric viability model. 6.1 Derivation of equilibrium solutions. 6.2 Conditions for stability of the equilibria. 7. Conditions for the increase of a new allele linked to a polymorphic locus. 8. Conditions for the simultaneous increase of new alleles at each of two linked loci. 9. A general condition for stable linkage disequilibrium when r is sufficiently small. IO. Sufficient conditions for the existence of a two-locus polymorphism. Discussion. Summary. Literature cited.

Differential Induction and Repair of Ultraviolet Damage Leading to True Reversions and External Suppressor Mutations of an Ochre Codon in ESCHERICHIA COLI B/R Wp2

Abstract: UCH of the published work on the mechanisms by which radiation-induced lesions result in genetic mutations in bacteria has involved the reversion to prototrophy of amino-acid requiring strains, in particular the tryptophan auxotroph Escherichia coli B/r WP2 isolated by WITKIN. It has been realised for some time that mutant prototrophs are not all true reversions to ‘wild type. HILL (1963), for example, foiund that some spontaneous and ultraviolet-induced prototrophs of B/r WP2 grew more slowly and were unstable. She suggested that they might be suppressor mutants. WITKIN (1963) also gave evidence that suppressor mutations, capable of cvvercoming at a single step auxotrophies at several loci, were induced by ultraviolet light (UV) under certain conditions. Unfortunately the difficulty in performing genetic analysis in the B family of E. coli has hitherto precluded a study of the involvement of true reversion and suppressor mutation in the several phenomena associated with radiation mutagenesis. Recently BRIDGES, DENNIS and PVIuNsoN (1967) showed that many prototrophs derived from B/r WP2 contain’ed suppressors capable of suppressing chain terminating codons in T4 phage, and a simple way of distinguishing suppressor mutants from true revertants was described. (Chain terminating codons UGA, UAG (“amber”) and UAA (“ochre”) appear to code for no amino acid and thus prevent the assembly of the polypeptide chain beyond the point at which they are situated in the messenger RNA.) In this paper we show that the suppressors in B/r WP2 are all ochre suppressors from which we infer thLat the parent B/r WP2 has an ochre (UAA) codon at a tryptophan locus. A sindar conclusion has been drawn by OSBORN and PERSON (1967). We also investigate the induction of true and suppressor mutations by UV under different conditions, and compare their relative susceptibility to various processes which have been described for the removal (or bypassing) of genetic damage.

Polygenic control of aldehyde oxidase in drosophila

Abstract: HEN extracts of wild-type Drosophila are electrophoresed on agar gels and the gels stained with a tetrazolium solution containing benzaldehyde, a formazan band is formed at a location not identical to the xanthine dehydrogenase (XDH) band ( COURTRIGHT 1966a). This was a surprising observation since benzaldehyde has been reported to serve as a substrate for XDH (GLASSMAN and MITCHELL 1959a). Since our new band is detected in extracts of ry flies, but not ma-1 flies, the evidence suggested that benzaldehyde was serving as a substrate for pyridoxal oxidase, a possibly related enzyme which also is present in ry and absent in ma-2 flies (FORREST, HANLY and LAGOWSKI 1961). The present paper presents genetic and biochemical evidence that the enzyme in question is neither pyridoxal oxidase nor XDH, but an aldehyde oxidase under similar genetic control. The enzyme also has some properties in common with the so-called ma-lf factor (GLASSMAN 1965, 1966), although its identity to the ma-l+ complementing factor is questionable.

Meiotic gene conversion in yeast tetrads and the theory of recombination

Abstract: ONVENTIONAL recombination theory has held that genetic recombination occurs after DNA replication, when each chromosome is composed of two chromatids; that crossing over involves a full-chromatid interaction between nonsister chromatids, and yields reciprocal products from breakage reunion events; and that either no crossing over occurs between sister chromatids, or if it occurs it is unrelated to homologous exchanges. Experience with this theory has shown that in a chromosome arm the occurrence of one exchange interferes with another exchange in an adjacent region. This has been manifested by detecting significantly fewer double crossovers than would be predicted on the assumption that individual exchanges occur independently of each other. Furthermore, among the multiple exchanges that do occur no evidence for chromatid interference has been found; two-, three-, and four-strand double exchanges are typically observed to occur in the expected 1:2: 1 ratio (PERKINS 1962). This theory has had the consequence that multiply recombined progeny derived from random sperm or random spores have been interpreted in terms of multiple exchanges between the genetic markers, even when the reciprocal products themselves have not been available for analysis. However, recombination need not be a reciprocal process. The initial report by MITCHELL (1955) of nonreciprocal recombination (gene conversion) was followed by others (reviewed by WHITEHOUSE and HASTINGS 1965) from which the following has become clear. (1 ) Recombination within a cistron may be nonrecip-

Distribution of DNA in heterochromatin and euchromatin of polytene nuclei of Drosophila hydei.

Abstract: HE concept that all cells of an organism contain the same quantity of DNA Tor a geometric multiple of it has been demonstrated in a large number of cases (SWIFT 1950; MIRSKY and RIS 195 1 ) . Many exceptions to this concept have been observed, some recent ones being those described by BEERMANN ( 1959,1966) and GEYER-DUSZYNSKA (1 966). For some organisms, it was demonstrated that the exception to the concept of DNA constancy could be explained by a different replication behavior of the euchromatin and heterochromatin (NUR 1966; KEYL and HAGELE 1966). In other organisms the validity of the concept is also in doubt. As long ago as 1934, HEITZ indicated that polytene nuclei of Drosophila virilis showed less heterochromatin than would be expected on the basis of visible heterochromatic structures present in diploid mitotically active nuclei. I t is generally accepted now that the absence of visible sex chromosomes or parts of them in polytene cells is mainly responsible for this deficit. These chromosomes show a heteropycnotic behavior during the mitotic cycle ( KAUFMANN 1934; COOPER 1959). Recently, RUDKIN (1 963) suggested three possibilities to explain such a shift of the euchromatin-heterochromatin ratio during the process of polytenization. RUDKIN proposed that either a slow replication of the heterochromatin in relation to the euchromatin, a delayed replication of the heterochromatin, or a partial replication of the heterochromatin caused such a shift. His observations supported the second possibility. The data indicated that the centric heterochromatin stops its replication soon after the process of polytenization begins (RUDKIN 1965). The present study deals with the replication of euchromatin and heterochromatin in polytene nuclei of the brain ganglion of Drosophila hydei. In this tissue, the centric heterochromatin shows a replication behavior during the first stages of polytenization that is different from that observed by RUDKIN in the salivary glands of Drosophila mlanogaster.

Spontaneous Mutations and Mutation Rates in the House Mouse

Abstract: HE frequency of occurrence of spontaneous mutations has been under investigation in the extensive mouse breeding colonies of the Jackson Laboratory since the autumn of 1963. The primary goal of this study is to estimate the spontaneous mutation rates, both forward and reverse, at each of five specific coat-color loci (non-agouti, a, brown, b, albino, c, dilute, d, and leaden, In). A secondary goal is to estimate an overall rate using all of the mutations found. Forward natural mutation rates based on large numbers of mice have been reported by RUSSELL (1963) and by CARTER, LYON, and PHILLIPS (1958). Preliminary estimates of rates in this study have been reported by GREEN, SCHLAGER and DICKIE (1965, 800,000 mice examined) and by SCHLAGER and DICKIE (1966, 1.5 million mice examined). This report will present estimates based on 3.5 million mice examined, representing ten million gene reproductions at the five specific coat-color loci, and 1.3 to 6.9 million gene reproductions at each of 40 other loci. These data were collected during the period from August 1963, through April, 1966. and include the data previously reported.

Continuously Distributed Factors Affecting Fitness

Abstract: UBBY and LEWONTIN (1966; LEWONTIN and HUBBY 1966) have demonstrated the probability that a population of diploid organisms can support more than an estimated 1000 polymorphisms. Their calculations agree with those of KIMURA and CROW (1964) and VAN VALEN (1963) in indicating that such widespread polymorphism cannot be maintained through single locus heterosis without entailing an absurdly high segregational load. The present paper is intended to demonstrate one way in which a high level of polymorphism might be maintained through selection favoring heterozygosis, with a modest segregational load. The segregational load will be considered as a component in the total variance in viability, rather than as a proportion of the population lost through selection. A mathematical model will be presented and several numerical examples will be given. For the sake of simplicity, one aspect of fitness will be treated as if it represented the sum of all as,pects of fitness; this aspect of fitness is zygote to adult viability, which can be treated as a probability. The simplifying assumption is that the genes being considered do not influence the fecundity of fertile adults. Very severe genetic effects, like severe environmental accidents, will result in death under most circumstances. Minor decrements in the probability of survival, such as those due to overdominance and to small fluctuations in the environment, are subject to many modifying factors, and are cumulative in nature. One of the principal factors affecting the expression of minor genetic and environmental effects is the environm'ental opportunity afforded as a result of the density of the population. In most natural populations, the reproductive potential far exceeds the environmental opportunity, and natural selection proceeds by culling to what the habitat can support. In the present model it is assumed that the genetic and nongenetic factors affecting the probability of survival are cumulative in each individual, and that individuals can be ordered in a linear array according to the sum of the factors affecting their survival. Natural selection proceeds by culling a proportion of the zygotes, taking those with the worst combinations of genes, environment and luck. The remainder, with better combinations of genes, environment and luck, survive to reproduce. Thus this is a threshold model. A few more simplifying assumptions must be made. I t is assumed that the probability of homozygosis is the same at each of N polymorphic loci, and that the selective advantage of the heterozygote is the same over any homozygote at

Transposition derivatives of an Hfr strain of Escherichia coli K-12.

Abstract: HE genome in Escherichia coli K-12 exists normally as one ring of doublestranded DNA (CAIRINS 1963). The fertility factor, F, is responsible for the ability of certain strains to act as genetic donors. F may exist as an autonomously replicating element (in Ff strains) or be integrated into and replicate with bacterial genome (in Hfr strains) (WOLLMAN, JACOB, and HAYES 1956). Multiplication of the autonomous F factor is inhibited by growth in a medium containing acridine orange: this converts an F+ culture to an Fculture. Acridine orange, however, does not affect the duplication of the integrated F factor (HIROTA 1960). Hfr cells transfer their chromosomes to suitable recipients in an oriented manner, beginning at the site of F factor integration (the origin). The F factor itself is the last marker transferred. Since there is spontaneous breakage of the donor chromosome during transfer, the probability of a marker being introduced into a recipient decreases with its distance from the origin of chromosome transfer (JACOB and WOLLMAN 1958). JACOB and ADELBERG (1 959) found that matings interrupted before the entire Hfr chromosome could be transferred still yielded a few recombinants for a distal Hfr marker. Many of these recombinants were able to donate this marker with high frequency to Frecipients, which became, in turn, high frequency donors. These were found to possess the selected distal marker associated with the F factor in an autonomous genetic element. Such elements are termed F-prime (F’) factors. I? factors, like F factors, may be removed from strains such as those described by JACOB and ADELBERG by growth in medium containing acridine orange (HIROTA and SNEATH 1961). CAMPBELL (1962) provided a framework for understanding the properties of I?’ factors when he proposed that autonomous elements (episomes) were circular structures. He suggested that episomes become associated with the bacterial chromosome by a single reciprocal crossover which integrates the episome into the chromosome. Thus, a reversal of the integrating exchange would release the

The location of genetic factors controlling a number of quantitative characters in wheat.

Abstract: technique for the location of genetic factors in the hexaploid wheat, Triticum A aestiuum (2n = 6x = 42), has been described in an earlier paper (LAW 1966). This technique exploited an inter-varietal chromosome-substitution line in which a single homologous pair of chromosomes in a recipient variety has been replaced by its homologues from a donor variety (SEARS 1953). By using this type of genetic material, it is possible to produce single chromosome heterozygotes, the derivatives of which provide estimates of the variation created by means of crossing over. It is the study of the amount and the type of this variation which allows the location of the determinants not only for qualitative characters but also for those having effects on quantitative aspects of the phenotype. This technique has been applied to the allelic differences existing between the two homologues of chromosome 7B found in the wheat varieties Chinese Spring and Hope. For the character days to ear emergence, LAW (1966) has shown that at least two factors, e, and e,, are responsible for the differences between these two homologues. Furthermore, el was shown to be closely linked to the centromere (LAW and WOLFE 1966), most probably located on the short arm, whereas e, must be at least 50 map-units from the centromere but on the long arm of this chromosome. Genes controlling purple culm ( P c ) , mildew resistance (mZ) and leaf-rust resistance (Zr) have also been located on this chromosome (LAW 1966; LAW and WOLFE 1966; LAW and JOHNSON, unpublished). The present paper describes the use of the same experimental material to determine the positions of factors controlling the quantitative characters yield, grain weight, height, tiller number and grain number.

The genetics of a mutable gene at the white locus of Drosophila melanogaster.

Abstract: LMOST coincidental with the rediscovery of Mendelism, genes of high sponA taneous mutation rate, often referred to as unstable, labile or mutable genes, were found. Such mutable genes, although not described as such, were identified in association with variegated phenotypes especially noticeable in plants as flower color variegation. R. A. EMERSON (1914, 191 7) from his studies of variegated pericarp color in maize was the first to suggest that the variegation was a consequence of frequent mutation of the gene for colorless pericarp, in short associated with a mutable gene. Subsequent studies all pointed to the conclusion that the high mutation rate of mutable genes was an inherent, autonomous property of the gene itself (see reviews by DEMEREC 1935 and STUBBE 1933). Especially noteworthy in this connection are the studies of DEMEREC who over a period of 15 years described and characterized several mutable genes in Drosophila virilis (summarized in DEMEREC 1941 ) . His detailed studies, particularly of the mutable miniature wing genes, led him to conclude that mutability, although influenced by specific genetic and environmental factors, was fundamentally a property of the mutable gene itself. More or less concurrently RHOADES (1938) described the then unique situation in which mutational instability was conferred upon the normally stable a gene in maize in the presence of the gene Dotted. We are indebted to MCCLINTOCK for the most extensive and detailed cytogenetic analysis of mutable genes in maize. Beginning with a report in 1950 ( MCCLINTOCK 1950, 195 1 ) , she was able to show in a brilliant series of investigations that high mutability of a number of genes in maize is controlled by genetic elements independent of the mutating gene itself. The diversity of interaction and control of the elements involved have been recently summarized and no further details need be elaborated here except to note that correctness of MCCLINTOCK’S conclusion has been amply verified by maize studies of BRINK and associates on PVu, by PETERSON on pg, a , and as and by NUFFER on bz, (MCCLINTOCK 1965). In contrast to the apparent widespread occurrence of mutable genes in maize, the mutable genes described by DEMEREC in D. viriZis represent the only other adequately investigated examples in multicellular organisms. Significantly, despite an intensive search for mutable genes by a number of investigators, especially in D. melanogaster, no good example has been described. Since DEMEREC’S mutable genes have been lost for some tme, it has not been possible to determine

A survey of new morphological mutants in neurospora crassa

Abstract: HIS investigation of morphological mutants in Neurospora crassa was underTtaken to examine a wide spectrum of such strains and to obtain information regarding their number and distribution in each of the seven linkage groups. This information, as well as a comparative study of their morphological characteristics, is important both theoretically and practically in facilitating further investigations of the biochemical defects involved. The present report describes the linkage to known markers of 90 morphological strains of independent origin. Of these, 58 have designated as new loci; the remainder appear to represent alleles either of the new or previously described loci. The order of the genes has been determined only in group V (MORGAN, GARNJOBST and TATUM 1967). The differences between strains in type of mycelial growth, both from the ascospore and upon transfer, and the distinct differences between some strains in hyphal morphology have suggested a new and practical classification of the morphological mutants. Six classes are defined, illustrated, and discussed.

Mutagenesis at a complex locus in Drosophila with the monofunctional alkylating agent, ethyl methanesulfonate.

Abstract: use of chemical mutagens in Drosophila usually results in the production T:mutants which are composed of mutant and nonmutant tissue. Mutants of this type are referred to as mosaic or fractional, as opposed to the complete or whole body mutants so commonly found in studies of X-ray mutagenesis. For the detection of mosaic and complete mutants, as well as for general mutagenesis studies, the most frequently used genetic system is the sex-linked lethal system. The use of this system( has, however, certain disadvantages, especially for the detection of mosaics when using a powerful mutagen such as ethyl methanesulfonate (EMS). One reason for this is the misclassification of double mosaics as completes; these “pseudlocompletes” arise from a two-hit event occurring at different sites along the two strands or subunits of a chromosome with one hit on each strand (EPLER 1966; JENKINS 1967). Another problem arises when more than one lethal hit occurs along the same strand or subunit of a chromosome. Such multiple-hit mutants vvould be classified as single-hit events, and they would result in an underestimation of the frequency of induced lethal mutations. Using a complex locus, such as dumpy, to study chemical mutagenesis has some advantages. If art intragenic double bilateral or complex mosaic were induced, two types of dumpy mutants would be produced-both detectable under most circumstances. This would permit a more accurate determination of the number of mutations arising at a given locus as well as the relative mutability of the various mutant sites within that locus. The dumpy locus, with its multiplicity of mutant sites and wide range of phenotypes, is an ideal locus for studying genetic fine structure and mutagenesis. The dumpy phenotype involves the thorax and its derivatives, the legs and wings, as well as an embryonic lethal effect. A mosaic dumpy mutant would be detected three times more frequently than would a mosaic eye mutant because of the larger number of cleavage nuclei which participate in the formation of thoracic tissue; however, probably only 75 % of the dumpy mosaics induced are actually detected in the somatic or germinal tissues because of the presence of mutant tissue in nondetectable areas such as the head or abdomen (LEE, KIRBY, and DEBNEY 1967). Nevertheless, compared to the sex-linked lethal system, dumpy is a preferable system to use because both the soma and the gonad can be analyzed for