bluuebunny/crossref_metadata_2025_split huggingface dataset:
Schizosaccharomyces pombe Ste7p Is Required for Both Promotion and Withholding of the Entry to Meiosis
Authors: Matsuyama Akihisa , Yabana Naoyuki , Watanabe Yoshinori , Yamamoto Masayuki 
Published: April 2021

Abstract
The fission yeast ste7 mutant cannot mate and undergo meiosis, but shows no defect in vegetative growth. We cloned and characterized the ste7 gene. The deduced ste7 gene product (Ste7p) was a protein of 569 amino acids with no significant similarity to other proteins. Transcription of ste7 was induced by nutrient starvation via the function of the transcription factor Ste11p. Disruption of the ste7 gene blocked both conjugation and meiosis, showing that Ste7p plays a positive role in these two processes, probably activating the pheromone signal pathway. Unexpectedly, overexpression of ste7+ promoted conjugation but inhibited meiosis in wild-type cells. The temperature-sensitive pat1-114 mutant underwent ectopic conjugation at the semirestrictive temperature when its genetic background was ste7+, whereas the same mutant initiated haploid meiosis when its genetic background was ste7Δ. Two-hybrid analysis suggested that Ste7p interacts physically with both Pat1p and Mei2p, which together constitute the major switch to initiate meiosis. Ste7p tagged with green fluorescent protein accumulated in haploid cells under nutrient starvation until they completed conjugation, but this protein disappeared when they were to enter meiosis. These observations suggest that Ste7p may have a function to suppress the onset of meiosis until the conjugation process has been duly completed.
The Impact of Lagging Strand Replication Mutations on the Stability of CAG Repeat Tracts in Yeast
Authors: Ireland Malia J , Reinke Shanda S , Livingston Dennis M 
Published: April 2021

Abstract
We have examined the stability of long tracts of CAG repeats in yeast mutants defective in enzymes suspected to be involved in lagging strand replication. Alleles of DNA ligase (cdc9-1 and cdc9-2) destabilize CAG tracts in the stable tract orientation, i.e., when CAG serves as the lagging strand template. In this orientation nearly two-thirds of the events recorded in the cdc9-1 mutant were tract expansions. While neither DNA ligase allele significantly increases the frequency of tract-length changes in the unstable orientation, the cdc9-1 mutant produced a significant number of expansions in tracts of this orientation. A mutation in primase (pri2-1) destabilizes tracts in both the stable and the unstable orientations. Mutations in a DNA helicase/deoxyribonuclease (dna2-1) or in two RNase H activities (rnh1Δ and rnh35Δ) do not have a significant effect on CAG repeat tract stability. We interpret our results in terms of the steps of replication that are likely to lead to expansion and to contraction of CAG repeat tracts.
Suppressors of a Cold-Sensitive Mutation in Yeast U4 RNA Define Five Domains in the Splicing Factor Prp8 That Influence Spliceosome Activation
Authors: Kuhn Andreas N , Brow David A 
Published: April 2021

Abstract
The highly conserved splicing factor Prp8 has been implicated in multiple stages of the splicing reaction. However, assignment of a specific function to any part of the 280-kD U5 snRNP protein has been difficult, in part because Prp8 lacks recognizable functional or structural motifs. We have used a large-scale screen for Saccharomyces cerevisiae PRP8 alleles that suppress the cold sensitivity caused by U4-cs1, a mutant U4 RNA that blocks U4/U6 unwinding, to identify with high resolution five distinct regions of PRP8 involved in the control of spliceosome activation. Genetic interactions between two of these regions reveal a potential long-range intramolecular fold. Identification of a yeast two-hybrid interaction, together with previously reported results, implicates two other regions in direct and indirect contacts to the U1 snRNP. In contrast to the suppressor mutations in PRP8, loss-of-function mutations in the genes for two other splicing factors implicated in U4/U6 unwinding, Prp44 (Brr2/Rss1/Slt22/Snu246) and Prp24, show synthetic enhancement with U4-cs1. On the basis of these results we propose a model in which allosteric changes in Prp8 initiate spliceosome activation by (1) disrupting contacts between the U1 snRNP and the U4/U6-U5 tri-snRNP and (2) orchestrating the activities of Prp44 and Prp24.
Bacillus thuringiensis (Bt) Toxin Susceptibility and Isolation of Resistance Mutants in the Nematode Caenorhabditis elegans
Authors: Marroquin Lisa D , Elyassnia Dino , Griffitts Joel S , Feitelson Jerald S , Aroian Raffi V 
Published: April 2021

Abstract
The protein toxins produced by Bacillus thuringiensis (Bt) are the most widely used natural insecticides in agriculture. Despite successful and extensive use of these toxins in transgenic crops, little is known about toxicity and resistance pathways in target insects since these organisms are not ideal for molecular genetic studies. To address this limitation and to investigate the potential use of these toxins to control parasitic nematodes, we are studying Bt toxin action and resistance in Caenorhabditis elegans. We demonstrate for the first time that a single Bt toxin can target a nematode. When fed Bt toxin, C. elegans hermaphrodites undergo extensive damage to the gut, a decrease in fertility, and death, consistent with toxin effects in insects. We have screened for and isolated 10 recessive mutants that resist the toxin's effects on the intestine, on fertility, and on viability. These mutants define five genes, indicating that more components are required for Bt toxicity than previously known. We find that a second, unrelated nematicidal Bt toxin may utilize a different toxicity pathway. Our data indicate that C. elegans can be used to undertake detailed molecular genetic analysis of Bt toxin pathways and that Bt toxins hold promise as nematicides.
The Use of a Genetic Algorithm for Simultaneous Mapping of Multiple Interacting Quantitative Trait Loci
Authors: Carlborg Örjan , Andersson Leif , Kinghorn Brian 
Published: April 2021

Abstract
Here we describe a general method for improving computational efficiency in simultaneous mapping of multiple interacting quantitative trait loci (QTL). The method uses a genetic algorithm to search for QTL in the genome instead of an exhaustive enumerative (“step-by-step”) search. It can be used together with any method of QTL mapping based on a genomic search, since it only provides a more efficient way to search the genome for QTL. The computational demand decreases by a factor of ~130 when using genetic algorithm-based mapping instead of an exhaustive enumerative search for two QTL in a genome size of 2000 cM using a resolution of 1 cM. The advantage of using a genetic algorithm increases further for larger genomes, higher resolutions, and searches for more QTL. We show that a genetic algorithm-based search has efficiency higher than or equal to a search method conditioned on previously identified QTL for all epistatic models tested and that this efficiency is comparable to that of an exhaustive search for multiple QTL. The genetic algorithm is thus a powerful and computationally tractable alternative to the exhaustive enumerative search for simultaneous mapping of multiple interacting QTL. The use of genetic algorithms for simultaneous mapping of more than two QTL and for determining empirical significance thresholds using permutation tests is also discussed.
Regulation of proboscipedia in Drosophila by Homeotic Selector Genes
Authors: Rusch Douglas B , Kaufman Thomas C 
Published: April 2021

Abstract
The gene proboscipedia (pb) is a member of the Antennapedia complex in Drosophila and is required for the proper specification of the adult mouthparts. In the embryo, pb expression serves no known function despite having an accumulation pattern in the mouthpart anlagen that is conserved across several insect orders. We have identified several of the genes necessary to generate this embryonic pattern of expression. These genes can be roughly split into three categories based on their time of action during development. First, prior to the expression of pb, the gap genes are required to specify the domains where pb may be expressed. Second, the initial expression pattern of pb is controlled by the combined action of the genes Deformed (Dfd), Sex combs reduced (Scr), cap'n'collar (cnc), and teashirt (tsh). Lastly, maintenance of this expression pattern later in development is dependent on the action of a subset of the Polycomb group genes. These interactions are mediated in part through a 500-bp regulatory element in the second intron of pb. We further show that Dfd protein binds in vitro to sequences found in this fragment. This is the first clear demonstration of autonomous positive cross-regulation of one Hox gene by another in Drosophila melanogaster and the binding of Dfd to a cis-acting regulatory element indicates that this control might be direct.
A Genome-Wide Departure From the Standard Neutral Model in Natural Populations of Drosophila
Authors: Andolfatto Peter , Przeworski Molly 
Published: April 2021

Abstract
We analyze nucleotide polymorphism data for a large number of loci in areas of normal to high recombination in Drosophila melanogaster and D. simulans (24 and 16 loci, respectively). We find a genome-wide, systematic departure from the neutral expectation for a panmictic population at equilibrium in natural populations of both species. The distribution of sequence-based estimates of 2Nc across loci is inconsistent with the assumptions of the standard neutral theory, given the observed levels of nucleotide diversity and accepted values for recombination and mutation rates. Under these assumptions, most estimates of 2Nc are severalfold too low; in other words, both species exhibit greater intralocus linkage disequilibrium than expected. Variation in recombination or mutation rates is not sufficient to account for the excess of linkage disequilibrium. While an equilibrium island model does not seem to account for the data, more complicated forms of population structure may. A proper test of alternative demographic models will require loci to be sampled in a more consistent fashion.
Retrotransposon Evolution in Diverse Plant Genomes
Authors: Langdon Tim , Seago Charlotte , Mende Michael , Leggett Michael , Thomas Huw , Forster John W , Thomas Howard , Jones R Neil , Jenkins Glyn 
Published: April 2021

Abstract
Retrotransposon or retrotransposon-like sequences have been reported to be conserved components of cereal centromeres. Here we show that the published sequences are derived from a single conventional Ty3-gypsy family or a nonautonomous derivative. Both autonomous and nonautonomous elements are likely to have colonized Poaceae centromeres at the time of a common ancestor but have been maintained since by active retrotransposition. The retrotransposon family is also present at a lower copy number in the Arabidopsis genome, where it shows less pronounced localization. The history of the family in the two types of genome provides an interesting contrast between “boom and bust” and persistent evolutionary patterns.
Evolution of Odorant Receptors Expressed in Mammalian Testes
Authors: Branscomb Aron , Seger Jon , White Raymond L 
Published: April 2021

Abstract
About 10% of mammalian odorant receptors are transcribed in testes, and odorant-receptor proteins have been detected on mature spermatozoa. Testis-expressed odorant receptors (TORs) are hypothesized to play roles in sperm chemotaxis, but they might also be ordinary nasal odorant receptors (NORs) that are expressed gratuitously in testes. Under the sperm-chemotaxis hypothesis, TORs should be subject to intense sexual selection and therefore should show higher rates of amino acid substitution than NORs, but under the gratuitous-expression hypothesis, TORs are misidentified NORs and therefore should evolve like other NORs. To test these predictions, we estimated synonymous and nonsynonymous divergences of orthologous NOR and TOR coding sequences from rat and mouse. Contrary to both hypotheses, TORs are on average more highly conserved than NORs, especially in certain domains of the OR protein. This pattern suggests that some TORs might perform internal nonolfactory functions in testes; for example, they might participate in the regulation of sperm development. However, the pattern is also consistent with a modified gratuitous-expression model in which NORs with specialized ligand specificities are both more highly conserved than typical NORs and more likely to be expressed in testes.
The Evolution of Haploid, Diploid and Polymorphic Haploid-Diploid Life Cycles: The Role of Meiotic Mutation
Authors: Hall David W 
Published: April 2021

Abstract
Here I present a simple population genetic model to investigate the evolution of polymorphic haploiddiploid life cycles. The key feature of the model is the assumption of mutation occurring during meiosis. I show that, in addition to regions favoring haploid or diploid life cycles, there are substantial regions of the parameter space under which polymorphic haploid-diploid life cycles are expected to evolve.
Statistical Models for Estimating the Genetic Basis of Repeated Measures and Other Function-Valued Traits
Authors: Jaffrézic Florence , Pletcher Scott D 
Published: April 2021

Abstract
The genetic analysis of characters that are best considered as functions of some independent and continuous variable, such as age, can be a complicated matter, and a simple and efficient procedure is desirable. Three methods are common in the literature: random regression, orthogonal polynomial approximation, and character process models. The goals of this article are (i) to clarify the relationships between these methods; (ii) to develop a general extension of the character process model that relaxes correlation stationarity, its most stringent assumption; and (iii) to compare and contrast the techniques and evaluate their performance across a range of actual and simulated data. We find that the character process model, as described in 1999 by Pletcher and Geyer, is the most successful method of analysis for the range of data examined in this study. It provides a reasonable description of a wide range of different covariance structures, and it results in the best models for actual data. Our analysis suggests genetic variance for Drosophila mortality declines with age, while genetic variance is constant at all ages for reproductive output. For growth in beef cattle, however, genetic variance increases linearly from birth, and genetic correlations are high across all observed ages.
Deficiency Mapping of Quantitative Trait Loci Affecting Longevity in Drosophila melanogaster
Authors: Pasyukova Elena G , Vieira Cristina , Mackay Trudy F C 
Published: April 2021

Abstract
In a previous study, sex-specific quantitative trait loci (QTL) affecting adult longevity were mapped by linkage to polymorphic roo transposable element markers, in a population of recombinant inbred lines derived from the Oregon and 2b strains of Drosophila melanogaster. Two life span QTL were each located on chromosomes 2 and 3, within sections 33E–46C and 65D–85F on the cytological map, respectively. We used quantitative deficiency complementation mapping to further resolve the locations of life span QTL within these regions. The Oregon and 2b strains were each crossed to 47 deficiencies spanning cytological regions 32F–44E and 64C–76B, and quantitative failure of the QTL alleles to complement the deficiencies was assessed. We initially detected a minimum of five and four QTL in the chromosome 2 and 3 regions, respectively, illustrating that multiple linked factors contribute to each QTL detected by recombination mapping. The QTL locations inferred from deficiency mapping did not generally correspond to those of candidate genes affecting oxidative and thermal stress or glucose metabolism. The chromosome 2 QTL in the 35B–E region was further resolved to a minimum of three tightly linked QTL, containing six genetically defined loci, 24 genes, and predicted genes that are positional candidates corresponding to life span QTL. This region was also associated with quantitative variation in life span in a sample of 10 genotypes collected from nature. Quantitative deficiency complementation is an efficient method for fine-scale QTL mapping in Drosophila and can be further improved by controlling the background genotype of the strains to be tested.
Maximum Likelihood Estimation of Recombination Rates From Population Data
Authors: Kuhner Mary K , Yamato Jon , Felsenstein Joseph 
Published: April 2021

Abstract
We describe a method for co-estimating r = C/μ (where C is the per-site recombination rate and μ is the per-site neutral mutation rate) and Θ = 4Neμ (where Ne is the effective population size) from a population sample of molecular data. The technique is Metropolis-Hastings sampling: we explore a large number of possible reconstructions of the recombinant genealogy, weighting according to their posterior probability with regard to the data and working values of the parameters. Different relative rates of recombination at different locations can be accommodated if they are known from external evidence, but the algorithm cannot itself estimate rate differences. The estimates of Θ are accurate and apparently unbiased for a wide range of parameter values. However, when both Θ and r are relatively low, very long sequences are needed to estimate r accurately, and the estimates tend to be biased upward. We apply this method to data from the human lipoprotein lipase locus.
CSE4 Genetically Interacts With the Saccharomyces cerevisiae Centromere DNA Elements CDE I and CDE II but Not CDE III: Implications for the Path of the Centromere DNA Around a Cse4p Variant Nucleosome
Authors: Keith Kevin C , Fitzgerald-Hayes Molly 
Published: April 2021

Abstract
Each Saccharomyces cerevisiae chromosome contains a single centromere composed of three conserved DNA elements, CDE I, II, and III. The histone H3 variant, Cse4p, is an essential component of the S. cerevisiae centromere and is thought to replace H3 in specialized nucleosomes at the yeast centromere. To investigate the genetic interactions between Cse4p and centromere DNA, we measured the chromosome loss rates exhibited by cse4 cen3 double-mutant cells that express mutant Cse4 proteins and carry chromosomes containing mutant centromere DNA (cen3). When compared to loss rates for cells carrying the same cen3 DNA mutants but expressing wild-type Cse4p, we found that mutations throughout the Cse4p histone-fold domain caused surprisingly large increases in the loss of chromosomes carrying CDE I or CDE II mutant centromeres, but had no effect on chromosomes with CDE III mutant centromeres. Our genetic evidence is consistent with direct interactions between Cse4p and the CDE I-CDE II region of the centromere DNA. On the basis of these and other results from genetic, biochemical, and structural studies, we propose a model that best describes the path of the centromere DNA around a specialized Cse4p-nucleosome.
A Directed Mutagenesis Screen in Drosophila melanogaster Reveals New Mutants That Influence hedgehog Signaling
Authors: Haines Nicola , van den Heuvel Marcel 
Published: April 2021

Abstract
The Hedgehog signaling pathway has been recognized as essential for patterning processes in development of metazoan animal species. The signaling pathway is, however, not entirely understood. To start to address this problem, we set out to isolate new mutations that influence Hedgehog signaling. We performed a mutagenesis screen for mutations that dominantly suppress Hedgehog overexpression phenotypes in the Drosophila melanogaster wing. We isolated four mutations that influence Hedgehog signaling. These were analyzed in the amenable wing system using genetic and molecular techniques. One of these four mutations affects the stability of the Hedgehog expression domain boundary, also known as the organizer in the developing wing. Another mutation affects a possible Hedgehog autoregulation mechanism, which stabilizes the same boundary.
Genetic and Developmental Analysis of X-Inactivation in Interspecific Hybrid Mice Suggests a Role for the Y Chromosome in Placental Dysplasia
Authors: Hemberger Myriam , Kurz Haymo , Orth Annie , Otto Sabine , Lüttges Angela , Elliott Rosemary , Nagy Andras , Tan Seong-Seng , Tam Patrick , Zechner Ulrich , Fundele Reinald H 
Published: April 2021

Abstract
It has been shown previously that abnormal placental growth, i.e., hyper- and hypoplasia, occurs in crosses and backcrosses between different mouse (Mus) species. A locus that contributes to this abnormal development has been mapped to the X chromosome. Unexpectedly, an influence of fetal sex on placental development has been observed, in that placentas attached to male fetuses tended to exhibit a more pronounced phenotype than placentas attached to females. Here, we have analyzed this sex dependence in more detail. Our results show that differences between male and female placental weights are characteristic of interspecific matings and are not observed in intraspecific Mus musculus matings. The effect is retained in congenic lines that contain differing lengths of M. spretus-derived X chromosome. Expression of the X-linked gene Pgk1 from the maternal allele only and lack of overall activity of two paternally inherited X-linked transgenes indicate that reactivation or lack of inactivation of the paternal X chromosome in trophoblasts of interspecific hybrids is not a frequent occurrence. Thus, the difference between male and female placentas seems not to be caused by faulty preferential X-inactivation. Therefore, these data suggest that the sex difference of placental weights in interspecific hybrids is caused by interactions with the Y chromosome.
Parallel Computation of a Maximum-Likelihood Estimator of a Physical Map
Authors: Bhandarkar Suchendra M , Machaka Salem A , Shete Sanjay S , Kota Raghuram N 
Published: April 2021

Abstract
Reconstructing a physical map of a chromosome from a genomic library presents a central computational problem in genetics. Physical map reconstruction in the presence of errors is a problem of high computational complexity that provides the motivation for parallel computing. Parallelization strategies for a maximum-likelihood estimation-based approach to physical map reconstruction are presented. The estimation procedure entails a gradient descent search for determining the optimal spacings between probes for a given probe ordering. The optimal probe ordering is determined using a stochastic optimization algorithm such as simulated annealing or microcanonical annealing. A two-level parallelization strategy is proposed wherein the gradient descent search is parallelized at the lower level and the stochastic optimization algorithm is simultaneously parallelized at the higher level. Implementation and experimental results on a distributed-memory multiprocessor cluster running the parallel virtual machine (PVM) environment are presented using simulated and real hybridization data.