bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of Mutations That Feminize Gametophytes of the Fern Ceratopteris
Authors: Strain Errol , Hass Barbara , Banks Jo Ann 
Published: April 2021

Abstract
Gametophytes of the fern Ceratopteris are either male or hermaphroditic. Their sex is epigenetically determined by the pheromone antheridiogen, which is secreted by the hermaphrodite and induces male and represses female development in other young, sexually undetermined gametophytes. To understand how antheridiogen represses the development of female traits at the genetic level, 16 new mutations that feminize the gametophyte in the presence of antheridiogen were identified and characterized. Seven are very tightly linked to the FEM1 locus previously described. Nine others define another locus named NOTCHLESS1 (NOT1), as several of the not1 mutants lack a meristem notch. Some not1 mutations also affect sporophyte development only when homozygous, indicating that the not1 mutations are recessive and that NOT1 is also required for normal sporophyte development. The epistatic interactions among FEM1, NOT1, and other sex-determining genes are described. This information was used to expand the genetic model of the sex-determining pathway in Ceratopteris. On the basis of this model, we can say that the presence of antheridiogen leads to the activation of the FEM1 gene, which not only promotes the differentiation of male traits, but also represses female development by activating the NOT1 gene. NOT1 represses the TRA genes necessary for the development of female traits in the gametophyte.
Probabilistic Prediction of Unknown Metabolic and Signal-Transduction Networks
Authors: Gomez Shawn M , Lo Shaw-Hwa , Rzhetsky Andrey 
Published: April 2021

Abstract
Regulatory networks provide control over complex cell behavior in all kingdoms of life. Here we describe a statistical model, based on representing proteins as collections of domains or motifs, which predicts unknown molecular interactions within these biological networks. Using known protein-protein interactions of Saccharomyces cerevisiae as training data, we were able to predict the links within this network with only 7% false-negative and 10% false-positive error rates. We also use Markov chain Monte Carlo simulation for the prediction of networks with maximum probability under our model. This model can be applied across species, where interaction data from one (or several) species can be used to infer interactions in another. In addition, the model is extensible and can be analogously applied to other molecular data (e.g., DNA sequences).
Estimating Recombination Rates From Population Genetic Data
Authors: Fearnhead Paul , Donnelly Peter 
Published: April 2021

Abstract
We introduce a new method for estimating recombination rates from population genetic data. The method uses a computationally intensive statistical procedure (importance sampling) to calculate the likelihood under a coalescent-based model. Detailed comparisons of the new algorithm with two existing methods (the importance sampling method of Griffiths and Marjoram and the MCMC method of Kuhner and colleagues) show it to be substantially more efficient. (The improvement over the existing importance sampling scheme is typically by four orders of magnitude.) The existing approaches not infrequently led to misleading results on the problems we investigated. We also performed a simulation study to look at the properties of the maximum-likelihood estimator of the recombination rate and its robustness to misspecification of the demographic model.
Mapping Quantitative Trait Loci Using Generalized Estimating Equations
Authors: Lange Christoph , Whittaker John C 
Published: April 2021

AbstractA number of statistical methods are now available to map quantitative trait loci (QTL) relative to markers. However, no existing methodology can simultaneously map QTL for multiple nonnormal traits. In this article we rectify this deficiency by developing a QTL-mapping approach based on generalized estimating equations (GEE). Simulation experiments are used to illustrate the application of the GEE-based approach.
Estimating the Total Number of Alleles Using a Sample Coverage Method
Authors: Huang Shu-Pang , Weir B S 
Published: April 2021

AbstractPreviously reported methods for estimating the number of different alleles at a single locus in a population have not described a useful general result. Using the number of alleles observed in a sample gives an underestimate for the true number of alleles. The similar problem of estimating the number of species in a population was first investigated in 1943. In this article we use the sample coverage method proposed by Chao and Lee in 1992 to estimate the number of alleles in a population when there are unequal allele frequencies. Simulation studies under the recurrent mutation model show that, for reasonable sample sizes, a significantly better estimate of the true number can be obtained than that using only the observed alleles. Results under the stepwise mutation model and infinite-allele model are presented. Possible applications include improving the characterization of the prior distribution for the allele frequencies, adjusting the estimates of genetic diversity, and estimating the range of microsatellite alleles.
On Prediction of Genetic Values in Marker-Assisted Selection
Authors: Lange Christoph , Whittaker John C 
Published: April 2021

Abstract
We suggest a new approximation for the prediction of genetic values in marker-assisted selection. The new approximation is compared to the standard approach. It is shown that the new approach will often provide substantially better prediction of genetic values; furthermore the new approximation avoids some of the known statistical problems of the standard approach. The advantages of the new approach are illustrated by a simulation study in which the new approximation outperforms both the standard approach and phenotypic selection.
Dissection of the Functions of the Saccharomyces cerevisiae RAD6 Postreplicative Repair Group in Mutagenesis and UV Sensitivity
Authors: Ćejka Petr , Vondrejs Vladimír , Storchová Zuzana 
Published: April 2021

Abstract
The RAD6 postreplicative repair group participates in various processes of DNA metabolism. To elucidate the contribution of RAD6 to starvation-associated mutagenesis, which occurs in nongrowing cells cultivated under selective conditions, we analyzed the phenotype of strains expressing various alleles of the RAD6 gene and single and multiple mutants of the RAD6, RAD5, RAD18, REV3, and MMS2 genes from the RAD6 repair group. Our results show that the RAD6 repair pathway is also active in starving cells and its contribution to starvation-associated mutagenesis is similar to that of spontaneous mutagenesis. Epistatic analysis based on both spontaneous and starvation-associated mutagenesis and UV sensitivity showed that the RAD6 repair group consists of distinct repair pathways of different relative importance requiring, besides the presence of Rad6, also either Rad18 or Rad5 or both. We postulate the existence of four pathways: (1) nonmutagenic Rad5/Rad6/Rad18, (2) mutagenic Rad5/Rad6 /Rev3, (3) mutagenic Rad6/Rad18/Rev3, and (4) Rad6/Rad18/Rad30. Furthermore, we show that the high mutation rate observed in rad6 mutants is caused by a mutator different from Rev3. From our data and data previously published, we suggest a role for Rad6 in DNA repair and mutagenesis and propose a model for the RAD6 postreplicative repair group.
Profiles of Adaptation in Two Similar Viruses
Authors: Holder K Kichler , Bull J J 
Published: April 2021

Abstract
The related bacteriophages ϕX174 and G4 were adapted to the inhibitory temperature of 44° and monitored for nucleotide changes throughout the genome. Phage were evolved by serial transfer at low multiplicity of infection on rapidly dividing bacteria to select genotypes with the fastest rates of reproduction. Both phage showed overall greater fitness effects per substitution during the early stages of adaptation. The fitness of ϕX174 improved from −0.7 to 5.6 doublings of phage concentration per generation. Five missense mutations were observed. The earliest two mutations accounted for 85% of the ultimate fitness gain. In contrast, G4 required adaptation to the intermediate temperature of 41.5° before it could be maintained at 44°. Its fitness at 44° increased from −2.7 to 3.2, nearly the same net gain as in ϕX174, but with three times the opportunity for adaptation. Seventeen mutations were observed in G4: 14 missense, 2 silent, and 1 intergenic. The first 3 missense substitutions accounted for over half the ultimate fitness increase. Although the expected pattern of periodic selective sweeps was the most common one for both phage, some mutations were lost after becoming frequent, and long-term polymorphism was observed. This study provides the greatest detail yet in combining fitness profiles with the underlying pattern of genetic changes, and the results support recent theories on the range of fitness effects of substitutions fixed during adaptation.
Cdc28 and Ime2 Possess Redundant Functions in Promoting Entry Into Premeiotic DNA Replication in Saccharomyces cerevisiae
Authors: Guttmann-Raviv Noga , Boger-Nadjar Elisabeth , Edri Iris , Kassir Yona 
Published: April 2021

Abstract
In the budding yeast Saccharomyces cerevisiae initiation and progression through the mitotic cell cycle are determined by the sequential activity of the cyclin-dependent kinase Cdc28. The role of this kinase in entry and progression through the meiotic cycle is unclear, since all cdc28 temperature-sensitive alleles are leaky for meiosis. We used a “heat-inducible Degron system” to construct a diploid strain homozygous for a temperature-degradable cdc28-deg allele. We show that this allele is nonleaky, giving no asci at the nonpermissive temperature. We also show, using this allele, that Cdc28 is not required for premeiotic DNA replication and commitment to meiotic recombination. IME2 encodes a meiosis-specific hCDK2 homolog that is required for the correct timing of premeiotic DNA replication, nuclear divisions, and asci formation. Moreover, in ime2Δ diploids additional rounds of DNA replication and nuclear divisions are observed. We show that the delayed premeiotic DNA replication observed in ime2Δ diploids depends on a functional Cdc28. Ime2Δ cdc28-4 diploids arrest prior to initiation of premeiotic DNA replication and meiotic recombination. Ectopic overexpression of Clb1 at early meiotic times advances premeiotic DNA replication, meiotic recombination, and nuclear division, but the coupling between these events is lost. The role of Ime2 and Cdc28 in initiating the meiotic pathway is discussed.
Analysis of a Mutant Exhibiting Conditional Sorting to Dense Core Secretory Granules in Tetrahymena thermophila
Authors: Bowman Grant R , Turkewitz Aaron P 
Published: April 2021

Abstract
The formation of dense core granules (DCGs) requires both the sorting of granule contents from other secretory proteins and a postsorting maturation process. The Tetrahymena thermophila strain SB281 fails to synthesize DCGs, and previous analysis suggested that the defect lay at or near the sorting step. Because this strain represents one of the very few mutants in this pathway, we have undertaken a more complete study of the phenotype. Genetic epistasis analysis places the defect upstream of those in two other characterized Tetrahymena mutants. Using immunofluorescent detection of granule content proteins, as well as GFP tagging, we describe a novel cytoplasmic compartment to which granule contents can be sorted in growing SB281 cells. Cell fusion experiments indicate that this compartment is not a biosynthetic intermediate in DCG synthesis. Sorting in SB281 is strongly conditional with respect to growth. When cells are starved, the storage compartment is degraded and de novo synthesized granule proteins are rapidly secreted. The mutation in SB281 therefore appears to affect DCG synthesis at the level of both sorting and maturation.
P-Element Repression in Drosophila melanogaster by Variegating Clusters of P-lacZ-white Transgenes
Authors: Ronsseray Stéphane , Boivin Antoine , Anxolabéhère Dominique 
Published: April 2021

Abstract
In Drosophila, clusters of P transgenes (P-lac-w) display a variegating phenotype for the w marker. In addition, X-ray-induced rearrangements of chromosomes bearing such clusters may lead to enhancement of the variegated phenotype. Since P-lacZ transgenes in subtelomeric heterochromatin have some P-element repression abilities, we tested whether P-lac-w clusters also have the capacity to repress P-element activity in the germline. One cluster (T-1), located on a rearranged chromosome (T2;3) and derived from a line bearing a variegating tandem array of seven P-lac-w elements, partially represses the dysgenic sterility (GD sterility) induced by P elements. This cluster also strongly represses in trans the expression of P-lacZ elements in the germline. This latter suppression shows a maternal effect. Finally, the combination of variegating P-lac-w clusters and a single P-lacZ reporter inserted in subtelomeric heterochromatic sequences at the X chromosome telomere (cytological site 1A) leads to strong repression of dysgenic sterility. These results show that repression of P-induced dysgenic sterility can be elicited in the absence of P elements encoding a polypeptide repressor and that a transgene cluster can repress the expression of a single homologous transgene at a nonallelic position. Implications for models of transposable element silencing are discussed.
Two-Locus Sampling Distributions and Their Application
Authors: Hudson Richard R 
Published: April 2021

Abstract
Methods of estimating two-locus sample probabilities under a neutral model are extended in several ways. Estimation of sample probabilities is described when the ancestral or derived status of each allele is specified. In addition, probabilities for two-locus diploid samples are provided. A method for using these two-locus probabilities to test whether an observed level of linkage disequilibrium is unusually large or small is described. In addition, properties of a maximum-likelihood estimator of the recombination parameter based on independent linked pairs of sites are obtained. A composite-likelihood estimator, for more than two linked sites, is also examined and found to work as well, or better, than other available ad hoc estimators. Linkage disequilibrium in the Xq28 and Xq25 region of humans is analyzed in a sample of Europeans (CEPH). The estimated recombination parameter is about five times smaller than one would expect under an equilibrium neutral model.
Mutations in sfdA and sfdB Suppress Multiple Developmental Mutations in Aspergillus nidulans
Authors: Kellner Ellen M , Adams Thomas H 
Published: April 2021

Abstract
Conidiophore morphogenesis in Aspergillus nidulans occurs in response to developmental signals that result in the activation of brlA, a well-characterized gene that encodes a transcription factor that is central to asexual development. Loss-of-function mutations in flbD and other fluffy loci have previously been shown to result in delayed development and reduced expression of brlA. flbD message is detectable during both hyphal growth and conidiation, and its gene product is similar to the Myb family of transcription factors. To further understand the regulatory pathway to brlA activation and conidiation, we isolated suppressor mutations that rescued development in strains with a flbD null allele. We describe here two new loci, designated sfdA and sfdB for suppressors of flbD, that bypass the requirement of flbD for development. sfd mutant alleles were found to restore developmental timing and brlA expression to strains with flbD deletions. In addition, sfd mutations suppress the developmental defects in strains harboring loss-of-function mutations in fluG, flbA, flbB, flbC, and flbE. All alleles of sfdA and sfdB that we have isolated are recessive to their wild-type alleles in diploids. Strains with mutant sfd alleles in otherwise developmentally wild-type backgrounds have reduced growth phenotypes and develop conidiophores in submerged cultures.
The Drosophila melanogaster Seminal Fluid Protein Acp62F Is a Protease Inhibitor That Is Toxic Upon Ectopic Expression
Authors: Lung Oliver , Tram Uyen , Finnerty Casey M , Eipper-Mains Marcie A , Kalb John M , Wolfner Mariana F 
Published: April 2021

Abstract
Drosophila melanogaster seminal fluid proteins stimulate sperm storage and egg laying in the mated female but also cause a reduction in her life span. We report here that of eight Drosophila seminal fluid proteins (Acps) and one non-Acp tested, only Acp62F is toxic when ectopically expressed. Toxicity to preadult male or female Drosophila occurs upon one exposure, whereas multiple exposures are needed for toxicity to adult female flies. Of the Acp62F received by females during mating, ~10% enters the circulatory system while ~90% remains in the reproductive tract. We show that in the reproductive tract, Acp62F localizes to the lumen of the uterus and the female's sperm storage organs. Analysis of Acp62F's sequence, and biochemical assays, reveals that it encodes a trypsin inhibitor with sequence and structural similarities to extracellular serine protease inhibitors from the nematode Ascaris. In light of previous results demonstrating entry of Acp62F into the mated female's hemolymph, we propose that Acp62F is a candidate for a molecule to contribute to the Acp-dependent decrease in female life span. We propose that Acp62F's protease inhibitor activity exerts positive protective functions in the mated female's reproductive tract but that entry of a small amount of this protein into the female's hemolymph could contribute to the cost of mating.
Differential Gene Silencing by trans-heterochromatin in Drosophila melanogaster
Authors: Csink Amy K , Bounoutas Alexander , Griffith Michelle L , Sabl Joy F , Sage Brian T 
Published: April 2021

Abstract
The brownDominant (bwD) allele contains a large insertion of heterochromatin leading to the trans-inactivation of the wild-type allele in bwD/bw+ heterozygous flies. This silencing is correlated with the localization of bw+ to a region of the interphase nucleus containing centric heterochromatin. We have used a series of transgene constructs inserted in the vicinity of the bw locus to demarcate both the extent of bwD influence along the chromosome and the relative sensitivities of various genes. Examples of regulatory regions that are highly sensitive, moderately sensitive, and insensitive were found. Additionally, by using the same transgene at increasing distances from the bwD insertion site in trans we were able to determine the range of influence of the heterochromatic neighborhood in terms of chromosomal distance. When the transgene was farther away from bw, there was, indeed, a tendency for it to be less trans-inactivated. However, insertion site also influenced silencing: a gene 86 kb away was trans-inactivated, while the same transgene 45 kb away was not. Thus location, distance, and gene-specific differences all influence susceptibility to trans-silencing near a heterochromatic neighborhood. These results have important implications for the ability of nuclear positioning to influence the expression of large blocks of a chromosome.
Molecular Characterization of the Mouse In(10)17Rk Inversion and Identification of a Novel Muscle-Specific Gene at the Proximal Breakpoint
Authors: Benson Kathleen F , Chada Kiran 
Published: April 2021

Abstract
Chromosomal rearrangements provide an important resource for molecular characterization of mutations in the mouse. In(10)17Rk mice contain a paracentric inversion of ~50 Mb on chromosome 10. Homozygous In(10)17Rk mice exhibit a pygmy phenotype, suggesting that the distal inversion breakpoint is within the pygmy locus. The pygmy mutation, originally isolated in 1944, is an autosomal recessive trait causing a dwarf phenotype in homozygous mice and has been mapped to the distal region of chromosome 10. The pygmy phenotype has subsequently been shown to result from disruption of the Hmgi-c gene. To identify the In(10)17Rk distal inversion breakpoint, In(10)17Rk DNA was subjected to RFLP analysis with single copy sequences derived from the wild-type pygmy locus. This analysis localized the In(10)17Rk distal inversion breakpoint to intron 3 of Hmgi-c and further study determined that a fusion transcript between novel 5′ sequence and exons 4 and 5 of Hmgi-c is created. We employed 5′ RACE to isolate the 5′ end of the fusion transcript and this sequence was localized to the proximal end of chromosome 10 between markers Cni-rs2 and Mtap7. Northern blot analysis of individual tissues of wild-type mice determined that the gene at the In(10)17Rk proximal inversion breakpoint is a novel muscle-specific gene and its disruption does not lead to a readily observable phenotype.
Structural Analysis of Aberrant Chromosomes That Occur Spontaneously in Diploid Saccharomyces cerevisiae: Retrotransposon Ty1 Plays a Crucial Role in Chromosomal Rearrangements
Authors: Umezu Keiko , Hiraoka Mina , Mori Masaaki , Maki Hisaji 
Published: April 2021

Abstract
The structural analysis of aberrant chromosomes is important for our understanding of the molecular mechanisms underlying chromosomal rearrangements. We have identified a number of diploid Saccharomyces cerevisiae clones that have undergone loss of heterozygosity (LOH) leading to functional inactivation of the hemizygous URA3 marker placed on the right arm of chromosome III. Aberrant-sized chromosomes derived from chromosome III were detected in ~8% of LOH clones. Here, we have analyzed the structure of the aberrant chromosomes in 45 LOH clones with a PCR-based method that determines the ploidy of a series of loci on chromosome III. The alterations included various deletions and amplifications. Sequencing of the junctions revealed that all the breakpoints had been made within repeat sequences in the yeast genome, namely, MAT-HMR, which resulted in intrachromosomal deletion, and retrotransposon Ty1 elements, which were involved in various translocations. Although the translocations involved different breakpoints on different chromosomes, all breakpoints were exclusively within Ty1 elements. Some of the resulting Ty1 elements left at the breakpoints had a complex construction that indicated the involvement of other Ty1 elements not present at the parental breakpoints. These indicate that Ty1 elements are crucially involved in the generation of chromosomal rearrangements in diploid yeast cells.