bluuebunny/crossref_metadata_2025 huggingface dataset:
Transposition of the Responder element (Rsp) of the Segregation distorter system (SD) to the X chromosome in Drosophila melanogaster.
Authors: Walker E S , Lyttle T W , Lucchesi J C
Published: January 2021

In order to test whether the meiotic drive system Segregation distorter (SD) can operate on the X chromosome to exclude it from functional sperm, we have transposed the Responder locus (Rsp) to this element. This was accomplished by inducing detachments of a compound-X chromosome in females carrying a Y chromosome bearing a Rsps allele. Six Responder-sensitive-bearing X chromosomes, with kappa values ranging from 0.90 to 1.00, were established as permanent lines. Two of these have been characterized more extensively with respect to various parameters affecting meiotic drive. SD males with a Responder-sensitive X chromosome produce almost exclusively male embryos, while those with a Rsp-Y chromosome produce almost exclusively female embryos. This provides a genetic system of great potential utility for the study of early sex-specific differentiation events as it allows the collection of large numbers of embryos of a given sex.
The PET54 gene of Saccharomyces cerevisiae: characterization of a nuclear gene encoding a mitochondrial translational activator and subcellular localization of its product.
Authors: Costanzo M C , Seaver E C , Fox T D
Published: January 2021

The product of the nuclear Saccharomyces cerevisiae gene PET54 is specifically required, along with at least two other nuclear gene products, for translation of the mitochondrial mRNA encoding subunit III of cytochrome c oxidase (coxIII). We have genetically mapped PET54 (to the right arm of chromosome VII, 4.8 cM centromere-distal to SUF15), and have biochemically characterized the gene and its product. We determined the nucleotide sequence of a 1.6-kb DNA fragment carrying PET54 and identified the PET54 reading frame by determining the sequence of an ochre mutant allele as well as frameshift and frameshift-revertant alleles of the gene. The wild-type PET54 gene encodes a slightly basic 293-amino acid protein. PET54 is expressed from two mRNAs, both with unusual features: a major transcript with an extremely short 5'-untranslated leader, and a minor transcript with a relatively long 5'-leader carrying three short open reading frames. Antiserum raised against a trpE-PET54 fusion protein was used to probe subcellular fractions. These experiments showed that the PET54 protein is specifically associated with mitochondria, suggesting that it is likely to act directly in coxIII translation.
A tripartite interaction among alleles of Notch, Delta, and Enhancer of split during imaginal development of Drosophila melanogaster.
Authors: Shepard S B , Broverman S A , Muskavitch M A
Published: January 2021

A dramatic example of a phenotypic interaction that involves neurogenic loci during Drosophila imaginal development is the synergistic impact of split (spl), a recessive allele of the Notch locus, and E(spl)D, a dominant gain-of-function allele of the Enhancer of split locus, on morphogenesis of the compound eye. Screens for mutations that relieve the enhancing effect of E(spl)D on spl have yielded three classes of mutations: intragenic revertants of the E(spl)D allele, extragenic suppressors that are allelic to the neurogenic gene Delta (Dl) and unlinked extragenic modifiers. Analysis of the suppression of the spl-E(spl)D interaction by various Dl alleles indicates that this modification is sensitive to the dosage of the Dl locus. This tripartite interaction illustrates the combinatorial action of N, Dl and E(spl) during imaginal development.
Pleiotropic stabilizing selection limits the number of polymorphic loci to at most the number of characters.
Authors: Hastings A , Hom C L
Published: January 2021

We demonstrate that, in a model incorporating weak Gaussian stabilizing selection on n additively determined characters, at most n loci are polymorphic at a stable equilibrium. The number of characters is defined to be the number of independent components in the Gaussian selection scheme. We also assume linkage equilibrium, and that either the number of loci is large enough that the phenotypic distribution in the population can be approximated as multivariate Gaussian or that selection is weak enough that the mean fitness of the population can be approximated using only the mean and the variance of the characters in the population. Our results appear to rule out antagonistic pleiotropy without epistasis as a major force in maintaining additive genetic variation in a uniform environment. However, they are consistent with the maintenance of variability by genotype-environment interaction if a trait in different environments corresponds to different characters and the number of different environments exceeds the number of polymorphic loci that affect the trait.
The genetics of catalase in Drosophila melanogaster: isolation and characterization of acatalasemic mutants.
Authors: Mackay W J , Bewley G C
Published: January 2021

Activated oxygen species have been demonstrated to be the important agents in oxygen toxicity by disrupting the structural and functional integrity of cells through lipid peroxidation events, DNA damage and protein inactivation. The biological consequences of free radical damage have long been hypothesized to be a causal agent in many aging-related diseases. Catalase (H2O2:H2O2 oxidoreductase; EC 1.15.1.1) is one of several enzymes involved in the scavenging of oxygen free radicals and free radical derivatives. The structural gene for catalase in Drosophila melanogaster has been localized to region 75D1-76A on chromosome 3L by dosage responses to segmental aneuploidy. This study reports the isolation of a stable deficiency, Df(3L)CatDH104(75C1-2;75F1), that uncovers the catalase locus and the subsequent isolation of six acatalasemic mutants. All catalase mutants are viable under standard culture conditions and recessive lethal mutations within the 75Cl-F1 interval have been shown not to affect catalase activity. Two catalase mutations are amorphic while four are hypomorphic alleles of the Cat+ locus. The lack of intergenic complementation between the six catalase mutations strongly suggests that there is only one functional gene in Drosophila. One acatalesemic mutation was mapped to position 3-47.0 which resides within the catalase dosage sensitive region. While complete loss of catalase activity confers a severe viability effect, residual levels are sufficient to restore viability to wild type levels. These results suggest a threshold effect for viability and offer an explanation for the general lack of phenotypic effects associated with the known mammalian acatalasemics.
Induction of mitochondrial DNA heteroplasmy by intra- and interspecific transplantation of germ plasm in Drosophila.
Authors: Matsuura E T , Chigusa S I , Niki Y
Published: January 2021

A new experimental system for inducing mitochondrial DNA heteroplasmy in Drosophila was developed. By transplanting the germ plasm of Drosophila melanogaster and Drosophila mauritiana into the posterior pole of the recipient eggs of D. melanogaster, it was possible to introduce foreign mitochondria into the recipient female germline. Heteroplasmic individuals containing both donor and recipient mtDNA were obtained in intra- and interspecific combinations at similar frequencies. The proportion of donor-derived mtDNA in the heteroplasmic individuals varied considerably from individual to individual irrespective of the donor species used. No significant decrease in or elimination of donor mtDNA was observed, and the heteroplasmic state in female germlines persisted for several generations. The present system should serve very much to promote the study and clarification of the transmission genetics of mtDNA in insects.
Does postzygotic isolation result from improper dosage compensation?
Authors: Orr H A
Published: January 2021

The X chromosome invariably has the largest effect on postzygotic isolation between animal species. One explanation of this pattern is that inviability and sterility result from a breakdown in the dosage compensation of X-linked genes in hybrids. In Drosophila, such breakdown could result from divergence of the genes used to assess the X/autosomal (X/A) ratio, and thus the sex, of an individual. I test this hypothesis by introducing mutant alleles of the Sex-lethal locus into Drosophila melanogaster-Drosophila simulans hybrids. These mutants "ignore" any perceived anomalous X/A ratio and thus can be used to ensure proper dosage compensation in hybrids. These mutants do not rescue hybrid viability or fertility, implying that postzygotic isolation in this hybridization does not result from a disruption of dosage compensation caused by divergence of the X/A counting system.
Apparent negative interference due to variation in recombination frequencies.
Authors: Säll T , Bengtsson B O
Published: January 2021

Variation in recombination frequencies may lead to a bias in the estimated interference value in a linkage experiment. Depending on the pattern of variation, the bias may be toward negative interference or toward positive interference, even when there is positive interference at the cytological level. In this paper we have mainly concentrated on the case of negative interference. We use models to quantify this effect when data are derived from a backcross experiment or from the selfing of F1 individuals. The effect is quantitatively similar in the two cases. There is an upper limit to the size the bias may reach for every given level of recombination. Two reported cases of negative interference in Drosophila and cultivated barley fall within this possible parameter range, i.e., the observed negative interference values could--at least in principle--be due solely to a variation in the recombination frequencies in the experiments.
The multivulva phenotype of certain Caenorhabditis elegans mutants results from defects in two functionally redundant pathways.
Authors: Ferguson E L , Horvitz H R
Published: January 2021

We previously identified Caenorhabditis elegans mutants in which certain of the six vulval precursor cells adopt fates normally expressed by other vulval precursor cells. These mutants define genes that appear to function in the response to an intercellular signal that induces vulval development. The multivulva (Muv) phenotype of one such mutant, CB1322, results from an interaction between two unlinked mutations, lin-8(n111) II and lin-9(n112) III. In this paper, we identify 18 new mutations, which are alleles of eight genes, that interact with either lin-8(n111) or lin-9(n112) to generate a Muv phenotype. None of these 20 mutations alone causes any vulval cell lineage defects. The "silent Muv" mutations fall into two classes; hermaphrodites carrying a mutation of each class are Muv, while hermaphrodites carrying two mutations of the same class have a wild-type vulval phenotype. Our results indicate that the Muv phenotype of these mutants results from defects in two functionally-redundant pathways, thereby demonstrating that redundancy can occur at the level of gene pathways as well as at the level of gene families.
Causes and consequences of variation in energy storage in Drosophila melanogaster.
Authors: Clark A G
Published: January 2021

Variation in energy storage pools has a proximate cause variation in rates of influx and efflux from the pools, and it may, as an ultimate consequence, result in variation in fitness. The possibility of this chain of causal links motivates attempts to quantify the genetic correlations among pool sizes, enzyme activities and fitness components. In this report, homogenates from 83 second chromosome replacement lines of Drosophila melanogaster were analyzed to determine the amounts of stored triacylglycerols and glycogen as well as the activities of 11 enzymes in relevant metabolic pathways. The viabilities and fecundities of these same lines were determined by a segregation test using the SM5 balancer chromosome. Analysis of covariance revealed significant differences among lines in quantities of stored triacylglycerols and glycogen, as well as in activities of the assayed enzymes. Significant broad-sense genetic correlations were detected for a number of enzyme pairs. Some of the traits showed a significant correlation with viability and fecundity, including lipid and glycogen storage. Multiple regression models that fitted fitness components to linear and quadratic functions of the biochemical traits yielded highly significant fits. The partial regression coefficients indicate the shape of the selection gradient, and instances of significant directional and stabilizing selection were detected.
Potential germline competition in animals and its evolutionary implications.
Authors: Hastings I M
Published: January 2021

Mutation, mitotic crossing over and mitotic gene conversion can create genetic diversity in otherwise uniform diploid cell lineages. In the germline this diversification may result in competition between diploid germline phenotypes, with subsequent biases in the frequency of alleles transmitted to the offspring. Sperm competition is a well documented feature of many higher organisms and a model is developed to quantify this process. Competition, and hence selection, can also occur by differential survival of diploid lineages before meiosis. It is concluded that under certain circumstances germline selection is an efficient means of eliminating unfavorable alleles from the population. This does not require differences in adult fertility or viability which is the usual mechanism cited as causing changes in gene frequency in a population. It is proposed that such competition may play a role in maintaining the efficiency of basic metabolic pathways.
Definition and properties of disequilibria within nuclear-mitochondrial-chloroplast and other nuclear-dicytoplasmic systems.
Authors: Schnabel A , Asmussen M A
Published: January 2021

We define and determine the interrelationships among five sets of disequilibrium parameters that measure two- and three-locus nonrandom associations in nuclear-dicytoplasmic systems. These assume a diploid nuclear locus and two haploid cytoplasmic loci, with special reference to nuclear-mitochondrial-chloroplast systems. Three sets of two-locus disequilibria measure the association between haplotypes at the two cytoplasmic loci (DMC) and associations between each cytoplasmic locus and nuclear alleles or genotypes (DM, D1M, D2M, D3M; DC, D1C, D2C, D3C). In addition, we present two classes of higher-order disequilibria that measure nonrandom allelic or genotypic associations involving all three loci. The first class quantifies associations between the nuclear locus and the two cytoplasmic loci taken jointly (DA/MC, DAA/MC, DAa/MC, Daa/MC, etc.), whereas the second measures only those associations remaining after all two-locus associations have been taken into account (DA/M/C, DAA/M/C, DAa/M/C, Daa/M/C). Based on combinations of these five sets of measures, we suggest a variety of parameterizations of three-locus, nuclear-dicytoplasmic systems. The dynamics of these disequilibria are then investigated under models of random and mixed mating, either with both cytoplasmic genomes inherited through the same parent or through opposite parents. Except for associations between the cytoplasmic haplotypes, which are constant when the two cytoplasmic genomes are inherited through the same parent, all disequilibria ultimately decay to zero. These randomizations do not necessarily occur monotonically, however, and in some cases are preceded by an initial increase in magnitude or sign change. For both inheritance patterns, the asymptotic decay rates are steadily retarded by increasing levels of self-fertilization. This behavior contrasts with that in the extreme case of complete selfing, for which only the heterozygote disequilibria always decay to zero. For all models considered, the dynamics of the two-locus cytonuclear subsystems are solely a function of the mating system, whereas the dynamical behavior and sign patterns of the cytoplasmic and three-locus disequilibria also depend strongly on the mode of cytoplasmic inheritance.
Nonrecombinant meiosis I nondisjunction in Saccharomyces cerevisiae induced by tRNA ochre suppressors.
Authors: Louis E J , Haber J E
Published: January 2021

The presence of the tRNA ochre suppressors SUP11 and SUP5 is found to induce meiosis I nondisjunction in the yeast Saccharomyces cerevisiae. The induction increases with increasing dosage of the suppressor and decreases in the presence of an antisuppressor. The effect is independent of the chromosomal location of SUP11. Each of five different chromosomes monitored exhibited nondisjunction at frequencies of 0.1%-1.1% of random spores, which is a 16-160-fold increase over wild-type levels. Increased nondisjunction is reflected by a marked increase in tetrads with two and zero viable spores. In the case of chromosome III, for which a 50-cM map interval was monitored, the resulting disomes are all in the parental nonrecombinant configuration. Recombination along chromosome III appears normal both in meioses that have no nondisjunction and in meioses for which there was nondisjunction of another chromosome. We propose that a proportion of one or more proteins involved in chromosome pairing, recombination or segregation are aberrant due to translational read-through of the normal ochre stop codon. Hygromycin B, an antibiotic that can suppress nonsense mutations via translational read-through, also induces nonrecombinant meiosis I nondisjunction. Increases in mistranslation, therefore, increase the production of aneuploids during meiosis. There was no observable effect of SUP11 on mitotic chromosome nondisjunction; however some disomes caused SUP11 ade2-ochre strains to appear white or red, instead of pink.
Mutations in nuclear gene cyt-4 of Neurospora crassa result in pleiotropic defects in processing and splicing of mitochondrial RNAs.
Authors: Dobinson K F , Henderson M , Kelley R L , Collins R A , Lambowitz A M
Published: January 2021

The nuclear cyt-4 mutants of Neurospora crassa have been shown previously to be defective in splicing the group I intron in the mitochondrial large rRNA gene and in 3' end synthesis of the mitochondrial large rRNA. Here, Northern hybridization experiments show that the cyt-4-1 mutant has alterations in a number of mitochondrial RNA processing pathways, including those for cob, coI, coII and ATPase 6 mRNAs, as well as mitochondrial tRNAs. Defects in these pathways include inhibition of 5' and 3' end processing, accumulation of aberrant RNA species, and inhibition of splicing of both group I introns in the cob gene. The various defects in mitochondrial RNA synthesis in the cyt-4-1 mutant cannot be accounted for by deficiency of mitochondrial protein synthesis or energy metabolism, and they suggest that the cyt-4-1 mutant is defective in a component or components required for processing and/or turnover of a number of different mitochondrial RNAs. Defective splicing of the mitochondrial large rRNA intron in the cyt-4-1 mutant may be a secondary effect of failure to synthesize pre-rRNAs having the correct 3' end. However, a similar explanation cannot be invoked to account for defective splicing of the cob pre-mRNA introns, and the cyt-4-1 mutation may directly affect splicing of these introns.
Genetic mapping in Xenopus laevis: eight linkage groups established.
Authors: Graf J D
Published: January 2021

Inheritance of alleles at 29 electrophoretically detected protein loci and one pigment locus (albinism) was analyzed in Xenopus laevis by backcrossing multiply heterozygous individuals generated by intersubspecies hybridization. Pairwise linkage tests revealed eight classical linkage groups. These groups have been provisionally numbered from 1 to 8 in an arbitrarily chosen order. Linkage group 1 includes ALB-2 (albumin), ADH-1 (alcohol dehydrogenase), NP (nucleoside phosphorylase), and ap (periodic albinism). Linkage group 2 contains ALB-1 and ADH-2, and probably is homeologous to group 1. Linkage group 3 comprises PEP-B (peptidase B), MPI-1 (mannosephosphate isomerase), SORD (sorbitol dehydrogenase), and mIDH-2 (mitochondrial isocitrate dehydrogenase). Linkage group 4 contains GPI-1 (glucosephosphate isomerase) and EST-4 (esterase 4). Linkage group 5 contains GPI-2 and PEP-D (peptidase D). Linkage group 6 comprises ACP-3 (acid phosphatase), sME (cytosolic malic enzyme), and GLO-2 (glyoxalase). Linkage group 7 consists of sSOD-1 (cytosolic superoxide dismutase), GPD-2 (glycerol-3-phosphate dehydrogenase), mME (mitochondrial malic enzyme), and the sex determining locus. Linkage group 8 includes FH (fumarate hydratase) and TRF (transferrin). Recombination frequencies between linked loci showed differences related to the genomic constitution (parental subspecies) and to the sex of the heterozygous parent. Independent assortment was observed between the duplicate ALB loci. This is true for the duplicate ADH, GLO, and MPI loci as well, supporting the view that these genes have been duplicated as part of a genome duplication that occurred in the evolutionary history of X. laevis. Comparative analysis of genetic maps reveals a possible conservation of several linkages from the Xenopus genome to the human genome.
Genetic resistance to viral infection: the molecular cloning of a Drosophila gene that restricts infection by the rhabdovirus sigma.
Authors: Contamine D , Petitjean A M , Ashburner M
Published: January 2021

The ref(2)P gene of Drosophila melanogaster has two common alleles, ref(2)Po which permits the infection of flies by the rhabdovirus sigma (sigma), and ref(2)Pp which is restrictive for sigma infection. This gene has been cloned by P element tagging and shown to code for two RNAs in adult flies. These RNAs are expressed in both males and females, but only the larger is expressed in ovaries. Both transcripts are shorter, by about 50 nucleotides, in flies carrying the ref(2)Pp allele than in those carrying ref(2)Po. The dominance relationships of these two alleles, and the fact that ref(2)Pnull alleles are permissive to sigma infection, suggest that the ref(2)Po product is antimorphic to that of the ref(2)Pp allele.
Genetic analysis of an interspecific hybrid swarm of Populus: occurrence of unidirectional introgression.
Authors: Keim P , Paige K N , Whitham T G , Lark K G
Published: January 2021

Restriction fragment length polymorphisms were used to distinguish genotypes of two species of Populus, P. fremontii ('Fremont') and P. angustifolia ('narrowleaf'). Both inter- and intraspecific polymorphisms were detected in these cottonwood trees. The interspecific variation was much greater than the intraspecific variation. This permitted identification of parental genotypes within individual trees of a hybrid swarm which exists in an overlap zone between the two species. Within this hybrid swarm, individual trees are either F1 hybrids or backcrosses with a pure 'narrowleaf' parent; no progeny were found that could be attributed to crossing between F1 hybrid trees, or to backcrossing between F1 hybrid trees and 'Fremont'.
Time for spreading of compensatory mutations under gene duplication.
Authors: Ohta T
Published: January 2021

Evolution by compensatory mutations is accelerated by gene duplication because selective constraint is relaxed by gene redundancy. A mutation is called compensatory if it corrects the effect of an earlier deleterious mutation. Without duplication, Kimura has shown that the time for spreading of compensatory mutations is much reduced by tight linkage between the two chromosomal sites of mutations. In this report, the time for spreading with gene duplication was studied by using the diffusion equation method of Kimura, together with computer simulations. It was shown that, when 2Nv- is much less than unity, the time for spreading is greatly shortened by gene duplication as compared with the case of complete linkage between the two sites of mutations, where 2N is the effective population size (haploid) and v- is the rate of compensatory mutations. However, if 2Nv- greater than 1, gene duplication is not effective for accelerating the evolution by such mutations.
The effect of change in population size on DNA polymorphism.
Authors: Tajima F
Published: January 2021

The expected number of segregating sites and the expectation of the average number of nucleotide differences among DNA sequences randomly sampled from a population, which is not in equilibrium, have been developed. The results obtained indicate that, in the case where the population size has changed drastically, the number of segregating sites is influenced by the size of the current population more strongly than is the average number of nucleotide differences, while the average number of nucleotide differences is affected by the size of the original population more severely than is the number of segregating sites. The results also indicate that the average number of nucleotide differences is affected by a population bottleneck more strongly than is the number of segregating sites.
Yeast intrachromosomal recombination: long gene conversion tracts are preferentially associated with reciprocal exchange and require the RAD1 and RAD3 gene products.
Authors: Aguilera A , Klein H L
Published: January 2021

A yeast intrachromosomal recombination system based on an inverted repeat has been designed to examine mitotic gene conversion tract length and the association of crossing over with gene conversion as a function of the conversion tract length. Short conversion tracts are found to be preferentially noncrossover while conversion tracts longer than 1.16 kb show a 50% association with crossover. Mutation in the excision repair gene RAD1 leads to a reduction in conversion tracts of at least 1.16 kb and a reduction in crossovers associated with conversion, regardless of the length of the conversion tract. Mutation in the excision repair gene RAD3, which encodes a DNA helicase, also leads to a reduction in conversion tracts of at least 1.16 kb, but has no effect on the frequency of associated crossovers. The roles of RAD1 and RAD3 in recombination are discussed.
Coordinately and differentially mutable activities of torpedo, the Drosophila melanogaster homolog of the vertebrate EGF receptor gene.
Authors: Clifford R J , Schüpbach T
Published: January 2021

The torpedo (top) locus of Drosophila encodes the fruitfly homolog of the vertebrate epidermal growth factor receptor gene and the neu proto-oncogene. We have isolated 13 top alleles in a screen for mutations failing to complement the female sterility of top, a recessive maternal effect allele that disrupts the establishment of the dorsoventral pattern of the egg shell and embryo. Several alleles recovered in this screen are zygotic lethal mutations; genetic analysis of these alleles has demonstrated that top is allelic to the embryonic lethal locus faint little ball. The 13 mutations recovered in our screens and 19 previously isolated top alleles have been genetically characterized through complementation tests with a series of hypomorphic and amorphic alleles. Nearly every top allele fails to complement the maternal effect sterility of top. Complementation tests show that the gene is required not only for oogenesis and embryogenesis, but also for pupal viability, for the growth of certain imaginal discs and for the patterning of specific ectodermal derivatives of the imaginal discs. Complementation analysis further demonstrates that the top lesions can be divided into general phenotypic categories: alleles affecting all gene activities in a coordinate manner, alleles preferentially affecting embryogenesis, alleles preferentially retaining oogenesis activity and alleles differentially affecting the development of specific imaginal disc derivatives. Correlations observed between the various developmental defects produced by top lesions suggest that the gene possesses several differentially, though not independently, mutable activities.
Identification and characterization of a mutation affecting the division arrest signaling of the pheromone response pathway in Saccharomyces cerevisiae.
Authors: Fujimura H
Published: January 2021

Mating pheromones, a- and alpha-factors, arrest the division of cells of opposite mating types, alpha and a cells, respectively. I have isolated a sterile mutant of Saccharomyces cerevisiae that is defective in division arrest in response to alpha-factor but not defective in morphological changes and agglutinin induction. The mutation was designated dac2 for division arrest control by mating pheromones. The dac2 mutation was closely linked to gal1 and was different from the previously identified cell type nonspecific sterile mutations (ste4, ste5, ste7, ste11, ste12, ste18 and dac1). Although dac2 cells had no phenotype in the absence of pheromones, they showed morphological alterations and divided continuously in the presence of pheromones. As a result, dac2 cells had a mating defect. The dac2 mutation could suppress the lethality caused by the disruption of the GPA1 gene (previously shown to encode a protein with similarity to the alpha subunit of mammalian G proteins). In addition, dac2 cells formed prezygotes with wild-type cells of opposite mating types, although they could not undergo cell fusion. These results suggest that the DAC2 product may control the signal for G-protein-mediated cell-cycle arrest and indicate that the synchronization of haploid yeast cell cycles by mating pheromones is essential for cell fusion during conjugation.
Detailed structure of the Drosophila melanogaster stellate genes and their transcripts.
Authors: Livak K J
Published: January 2021

The X-linked Stellate locus contains two major size classes of a tandemly repeated gene. An example of each class has been sequenced. The steady-state level of Stellate RNA is much higher in XO testis than in XY testis. Sequencing of six cDNA clones derived from XO testis RNA shows that there are two major introns in the Stellate genes. Primer extension and RNase protection analyses show that these introns are spliced much more efficiently in XO than in XY testis. These results also indicate the major transcriptional start site for Stellate RNA. P element transformation results with a marked Stellate gene demonstrate that at least one of the genes sequenced contains a functional promoter, which generates low levels of RNA in XY testis and high levels of RNA in XO testis. This promoter does not contain a TATA element in the -30 region relative to the transcriptional start. Previous results had implicated a specific region of the Y chromosome, designated here as the Su(Ste) locus, in the control of the Stellate genes on the X. Analysis using segmental Y deficiencies shows that the Su(Ste) region suppresses both the high levels and efficient splicing of Stellate RNA.
Evidence for horizontal transmission of the P transposable element between Drosophila species.
Authors: Daniels S B , Peterson K R , Strausbaugh L D , Kidwell M G , Chovnick A
Published: January 2021

Several studies have suggested that P elements have rapidly spread through natural populations of Drosophila melanogaster within the last four decades. This observation, together with the observation that P elements are absent in the other species of the melanogaster subgroup, has lead to the suggestion that P elements may have entered the D. melanogaster genome by horizontal transmission from some more distantly related species. In an effort to identify the potential donor in the horizontal transfer event, we have undertaken an extensive survey of the genus Drosophila using Southern blot analysis. The results showed that P-homologous sequences are essentially confined to the subgenus Sophophora. The strongest P hybridization occurs in species from the closely related willistoni group. A wild-derived strain of D. willistoni was subsequently selected for a more comprehensive molecular examination. As part of the analysis, a complete P element was cloned and sequenced from this line. Its nucleotide sequence was found to be identical to the D. melanogaster canonical P, with the exception of a single base substitution at position 32. When the cloned element was injected into D. melanogaster embryos, it was able to both promote transposition of a coinjected marked transposon and induce singed-weak mutability, thus demonstrating its ability to function as an autonomous element. The results of this study suggest that D. willistoni may have served as the donor species in the horizontal transfer of P elements to D. melanogaster.
Mechanisms of activation of the cryptic cel operon of Escherichia coli K12.
Authors: Parker L L , Hall B G
Published: January 2021

The cel (cellobiose utilization) operon of Escherichia coli K12 is not expressed in the wild-type organism. However, mutants that can express the operon and thereby utilize the beta-glucoside sugars cellobiose, arbutin and salicin are easily isolated. Two kinds of mutations are capable of activating the operon. The first involves mutations that allow the repressor to recognize the substrates cellobiose, arbutin and salicin as inducers. We have identified the sequence changes in five different active alleles and found those differences to be single base pair changes at one of two lysine codons in the repressor gene. The second kind of mutation involves the integration of the insertion sequences IS1, IS2 or IS5 into a 108-bp region 72-180 bp upstream of the start of transcription. Integration occurs at several different sites and in different orientations. Transcription of the cel operon begins at the same base pair in all mutants examined. Of 44 independent cel+ mutants, 27 were activated by point mutations and 17 were activated by insertion sequences. The preferred mechanism of activation appears to be strain dependent, since one of the parents yielded 94% insertionally activated alleles, while another yielded 100% point mutation activated alleles.
Pleiotropic models of quantitative variation.
Authors: Barton N H
Published: January 2021

It is widely held that each gene typically affects many characters, and that each character is affected by many genes. Moreover, strong stabilizing selection cannot act on an indefinitely large number of independent traits. This makes it likely that heritable variation in any one trait is maintained as a side effect of polymorphisms which have nothing to do with selection on that trait. This paper examines the idea that variation is maintained as the pleiotropic side effect of either deleterious mutation, or balancing selection. If mutation is responsible, it must produce alleles which are only mildly deleterious (s approximately 10(-3)), but nevertheless have significant effects on the trait. Balancing selection can readily maintain high heritabilities; however, selection must be spread over many weakly selected polymorphisms if large responses to artificial selection are to be possible. In both classes of pleiotropic model, extreme phenotypes are less fit, giving the appearance of stabilizing selection on the trait. However, it is shown that this effect is weak (of the same order as the selection on each gene): the strong stabilizing selection which is often observed is likely to be caused by correlations with a limited number of directly selected traits. Possible experiments for distinguishing the alternatives are discussed.
DNA fingerprints applied to gene introgression in breeding programs.
Authors: Hillel J , Schaap T , Haberfeld A , Jeffreys A J , Plotzky Y , Cahaner A , Lavi U
Published: January 2021

An application of DNA fingerprints (DFP) for gene introgression in breeding programs of both farm animals and plants is proposed. DFP loci, detectable by minisatellite probes, are extremely polymorphic. Individuals have unique patterns of DFP and thus can be selected for maximal genomic similarity to the recipient line, and minimal similarity to the donor line, using their DFP patterns as the criterion for similarity. This genomic selection (GS) can be performed at generations BC1, BC2 or both, and thus significantly reduce the required number of backcross generations in introgression breeding programs. The association between genomic and DFP similarity is demonstrated. Theoretical distributions and variances of the relative percentages of the donor and recipient genomes as the basis for the GS approach are presented.
Isolation and characterization of mutants constitutive for expression of the fbp1 gene of Schizosaccharomyces pombe.
Authors: Hoffman C S , Winston F
Published: January 2021

Transcription of the fbp1 gene of Schizosaccharomyces pombe, encoding fructose-1,6-bisphosphatase, is glucose repressible. We have constructed two hybrid genes, containing the fbp1 promoter, that allow selection for mutations that alter transcriptional regulation of fbp1. Strains carrying fbp1-ura4 and fbp1-lacZ fusions are phenotypically Ura-, resistant to 5-fluoro-orotic acid, and express a low level of beta-galactosidase activity when grown under repressing conditions (8% glucose). By selecting for Ura+ strains grown under repressing conditions, we have isolated 187 independent mutants that constitutively express the fbp1-ura4 fusion. These mutants identify ten complementation groups that represent ten unlinked git (glucose insensitive transcription) genes. The git gene products are required in trans for glucose repression of expression from the fbp1 promoter since these mutations also alter expression of the fbp1-lacZ fusion. We have shown that transcription of the wild type fbp1 gene in most git mutants is elevated to a level consistent with the increased expression of the fbp1-lacZ hybrid gene. Mutations in some git genes confer additional phenotypes such as slow growth, temperature-sensitive lethality and reduced spore viability. Therefore, some of these genes are likely to encode factors that are of general importance for S. pombe transcription.
Recent appearance and molecular characterization of mitochondrial DNA deletions within a defined nematode pedigree.
Authors: Hyman B C , Slater T M
Published: January 2021

The mitochondrial genome of Romanomermis culicivorax, a parasitic nematode of mosquitoes, contains an amplified 3.0-kilobase (kb) locus organized as direct repeats and as noncontiguous, inverted copies. These amplified sequences are actively undergoing rearrangement. One recent event has resulted in a 1133-base pair (bp) deletion located entirely within a single amplified segment. The deletion junction occurs between two imperfect 58-bp repeats, implicating strand pairing in this alteration. A second event has generated mitochondrial DNA (mtDNA) forms differing by a single, intact 3.0-kb repeating unit. By analyzing molecules derived from independently reared subcultures, it appears these new mtDNA forms arose within the last 170 nematode generations. Our results indicate that the occurrence and selection of novel animal mitochondrial genomes can now be studied in this experimentally manipulable nematode system.
Developmental expression of the glucose dehydrogenase gene in Drosophila melanogaster.
Authors: Cox-Foster D L , Schonbaum C P , Murtha M T , Cavener D R
Published: January 2021

The Gld gene of Drosophila melanogaster is transiently expressed during every stage of development. The temporal pattern of Gld expression is highly correlated with that of ecdysteroids. Exogeneous treatment of third instar larvae with 20-hydroxyecdysone induces the accumulation of Gld mRNA in the hypoderm and anterior spiracular gland cells. During metamorphosis Gld is expressed in a variety of tissues derived from the ectoderm. In the developing reproductive tract, Gld mRNA accumulates in the female spermathecae and oviduct and in the male ejaculatory duct and ejaculatory bulb. These four organs are derived from closely related cell lineages in the genital imaginal disc. Since the expression of Gld is not required for the development of these reproductive structures, this spatial pattern of expression is most likely a fortuitous consequence of a shared regulatory factor in this cell lineage. At the adult stage a high level of the Gld mRNA is only observed in the male ejaculatory duct.
Genetic analysis of the adenosine3 (Gart) region of the second chromosome of Drosophila melanogaster.
Authors: Tiong S Y , Nash D
Published: January 2021

The Gart gene of Drosophila melanogaster is known, from molecular biological evidence, to encode a polypeptide that serves three enzymatic functions in purine biosynthesis. It is located in polytene chromosome region 27D. One mutation in the gene (ade3(1)) has been described previously. We report here forty new ethyl methanesulfonate-induced mutations selected aga!nst a synthetic deficiency of the region from 27C2-9 to ++28B3-4. The mutations were characterized cytogenetically and by complementation analysis. The analysis apparently identifies 12 simple complementation groups. In addition, two segments of the chromosome exhibit complex complementation behavior. The first, the 28A region, gave three recessive lethals and also contains three known visible mutants, spade (spd), Sternopleural (Sp) and wingless (wg); a complex pattern of genetic interaction in the region incorporates both the new and the previously known mutants. The second region is at 27D, where seven extreme semilethal mutations give a complex complementation pattern that also incorporates ade3(1). Since ade3(1) is defective in one of the enzymatic functions encoded in the Gart gene, we assume the other seven also affect the gene. The complexity of the complementation pattern presumably reflects the functional complexity of the gene product. The phenotypic effects of the mutants at 27D are very similar to those described for ade2 mutations, which also interrupt purine biosynthesis.
Interactions of vestigial and scabrous with the Notch locus of Drosophila melanogaster.
Authors: Rabinow L , Birchler J A
Published: January 2021

Interactions are described between the Notch locus of Drosophila melanogaster, and two other loci, scabrous and vestigial, which respectively affect the eyes and wings. The Notch locus is responsible for mediating decisions of cell fate throughout development in many different tissues. Mutations and duplications of vestigial and scabrous alter the severity of phenotypes associated with Notch mutations and duplications in a manner that is essentially tissue- and allele-specific. These interactions indicate that the products of vestigial and scabrous act in conjunction with Notch to stimulate the differentiation of specific cell types.
Mutations in polycombeotic, a Drosophila polycomb-group gene, cause a wide range of maternal and zygotic phenotypes.
Authors: Phillips M D , Shearn A
Published: January 2021

The polycomb-group genes, a set of genes characterized by mutations that cause similar phenotypes and dosage-dependent interactions, are required for the normal expression of segment-specific homeotic loci. Here we report that polycombeotic (formerly 1(3)1902), originally identified by a lethal mutation that causes a small-disc phenotype, is also a member of this group of essential genes. Adults homozygous for temperature-sensitive pco alleles that were exposed to the restrictive temperature during larval life display the second and third leg to first leg transformation characteristic of polycomb-group mutants. Adult females homozygous for temperature-sensitive alleles exposed to the restrictive temperature during oogenesis produce embryos that show anterior segments with structures normally unique to the eighth abdominal segment, another transformation characteristic of polycomb-group mutants. Mutations in the polycombeotic gene also cause defects not reported for mutations in other polycomb-group genes. Females homozygous for the most extreme temperature-sensitive allele are sterile, and larvae homozygous for null alleles have small imaginal discs and reduced frequencies of mitotic figures in the brain. Dominant mutations originally identified as enhancers or suppressors of zeste are gain-of-function alleles of polycombeotic. The type and variety of defects displayed by different mutations in this gene indicate that the product might be involved in chromosome structure and/or function.
Mixed segregation of chromosomes during single-division meiosis of Saccharomyces cerevisiae.
Authors: Sharon G , Simchen G
Published: January 2021

Normal meiosis consists of two consecutive cell divisions in which all the chromosomes behave in a concerted manner. Yeast cells homozygous for the mutation cdc5, however, may be directed through a single meiotic division of a novel type. Dyad analysis of a cdc5/cdc5 strain with centromere-linked markers on four different chromosomes has shown that, in these meioses, some chromosomes within a given cell segregate reductionally whereas others segregate equationally. The choice between the two types of segregation in these meioses is made individually by each chromosome pair. Different chromosome pairs exhibit different segregation tendencies. Similar results were obtained for cells homozygous for cdc14.
Is there selection on RFLP differences in mitochondrial DNA?
Authors: Nigro L , Prout T
Published: January 2021

Experimental populations of Drosophila simulans were established for the purpose of detecting the presence or absence of selection on a restriction fragment length polymorphism in mitochondrial DNA (mtDNA). It was then discovered that the founding strains differed with respect to the Rickettsia-mediated incompatibility system in this species, which is maternally transmitted together with the mtDNA differences. A population model was constructed using the known fitness effects of the incompatibility system, with the result that the population trajectories can be completely explained by the effects of the microorganism with no need to invoke selection on mtDNA. The strong conclusion is that in this case we can rule out the strong selection proposed by MacRae and Anderson to explain the "dramatic mtDNA changes" in their Drosophila pseudoobscura populations. The population theory used for the experiments is discussed in the context of natural populations. Estimated parameters include the possibility that with two populations, one with the organism and one without it, there may be no bias as to which will invade the other, which in turn suggests no global tendency for the infection to spread or decline.
Mathematical models of gene amplification with applications to cellular drug resistance and tumorigenicity.
Authors: Kimmel M , Axelrod D E
Published: January 2021

An increased number of copies of specific genes may offer an advantage to cells when they grow in restrictive conditions such as in the presence of toxic drugs, or in a tumor. Three mathematical models of gene amplification and deamplification are proposed to describe the kinetics of unstable phenotypes of cells with amplified genes. The models differ in details but all assume probabilistic mechanisms of increase and decrease in gene copy number per cell (gene amplification/deamplification). Analysis of the models indicates that a stable distribution of numbers of copies of genes per cell, observed experimentally, exists only if the probability of deamplification exceeds the probability of amplification. The models are fitted to published data on the loss of methotrexate resistance in cultured cell lines, due to the loss of amplified dihydrofolate reductase gene. For two mouse cell lines unstably resistant to methotrexate the probabilities of amplification and deamplification of the dihydrofolate reductase gene on double minute chromosomes are estimated to be approximately 2% and 10%, respectively. These probabilities are much higher than widely presumed. The models explain the gradual disappearance of the resistant phenotype when selective pressure is withdrawn, by postulating that the rate of deamplification exceeds the rate of amplification. Thus it is not necessary to invoke a growth advantage of nonresistant cells which has been the standard explanation. For another analogous process, the loss of double minute chromosomes containing the myc oncogene from SEWA tumor cells, the growth advantage model does seem to be superior to the amplification and deamplification model. In a more theoretical section of the paper, it is demonstrated that gene amplification/deamplification can result in reduction to homozygosity, such as is observed in some tumors. Other applications are discussed.