bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frequent Meiotic Recombination Between the Ends of Truncated Chromosome Fragments of Saccharomyces cerevisiae
Authors: Arbel Tamar , Shemesh Ronen , Simchen Giora 
Published: April 2021

Abstract
A single truncated chromosome fragment (TCF) in diploid cells undergoes frequent ectopic recombination during meiosis between markers located near the ends of the fragment. Tetrads produced by diploids with a single TCF show frequent loss of one of the two markers. This marker loss could result either from recombination of the TCF with one of the two copies of the chromosome from which it was derived or from ectopic recombination between the ends of the TCF. The former would result in shortening of a normal chromosome and lethality in one of the four spores. The high frequency of marker loss in tetrads with four viable spores supports recombination between the TCF ends as the main source of marker loss. Most of the spore colonies that display TCF marker loss contained a TCF with the same marker on both ends. Deletion of most of the pBR322 sequences distal to the marker at one of the subtelomeric regions of the TCF did not reduce the overall frequency of recombination between the ends, but affected the loss of one marker significantly more than the other. We suggest that the mechanism by which the duplication of one end marker and loss of the other occurs is based on association and recombination between the ends of the TCF.
SEL-5, A Serine/Threonine Kinase That Facilitates lin-12 Activity in Caenorhabditis elegans
Authors: Fares Hanna , Greenwald Iva 
Published: April 2021

Abstract
Ligands present on neighboring cells activate receptors of the LIN-12/Notch family by inducing a proteolytic cleavage event that releases the intracellular domain. Mutations that appear to eliminate sel-5 activity are able to suppress constitutive activity of lin-12(d) mutations that are point mutations in the extracellular domain of LIN-12, but cannot suppress lin-12(intra), the untethered intracellular domain. These results suggest that sel-5 acts prior to or during ligand-dependent release of the intracellular domain. In addition, sel-5 suppression of lin-12(d) mutations is tissue specific: loss of sel-5 activity can suppress defects in the anchor cell/ventral uterine precursor cell fate decision and a sex myoblast/coelomocyte decision, but cannot suppress defects in two different ventral hypodermal cell fate decisions in hermaphrodites and males. sel-5 encodes at least two proteins, from alternatively spliced mRNAs, that share an amino-terminal region and differ in the carboxy-terminal region. The amino-terminal region contains the hallmarks of a serine/threonine kinase domain, which is most similar to mammalian GAK1 and yeast Pak1p.
Cosuppression of I Transposon Activity in Drosophila by I-Containing Sense and Antisense Transgenes
Authors: Jensen Silke , Gassama Marie-Pierre , Heidmann Thierry 
Published: April 2021

Abstract
We have previously shown that the activity of functional I elements introduced into Drosophila devoid of such elements can be repressed by transgenes containing an internal nontranslatable part of the I element itself and that this repressing effect presents features characteristic of homology-dependent gene silencing or cosuppression. Here we show that transgenes containing a fragment of the I element in antisense orientation induce I-element silencing with the same characteristic features as the corresponding sense construct: namely, repression takes several generations to be fully established, with similar rates for sense and antisense constructs, and it is only maternally transmitted, with reversal of the effect through paternal transmission. We also show that transcription of the transgenes is necessary to produce the silencing effect and that repression can be maintained for at least one generation following elimination of the transgenes, thus strongly suggesting that a transgene product and not the transgene per se is the essential intermediate in the silencing effect. The data presented strongly support models in which the repressing effect of antisense transcripts involves the same mechanisms as cosuppression by sense constructs and emphasize the role of symmetrically acting nucleic acid structures in mediating repression.
Genetic Analyses of Visual Pigments of the Pigeon (Columba livia)
Authors: Kawamura Shoji , Blow Nathan S , Yokoyama Shozo 
Published: April 2021

Abstract
We isolated five classes of retinal opsin genes rh1Cl, rh2Cl, sws1Cl, sws2Cl, and lwsCl from the pigeon; these encode RH1Cl, RH2Cl, SWS1Cl, SWS2Cl, and LWSCl opsins, respectively. Upon binding to 11-cis-retinal, these opsins regenerate the corresponding photosensitive molecules, visual pigments. The absorbance spectra of visual pigments have a broad bell shape with the peak, being called λmax. Previously, the SWS1Cl opsin cDNA was isolated from the pigeon retinal RNA, expressed in cultured COS1 cells, reconstituted with 11-cis-retinal, and the λmax of the resulting SWS1Cl pigment was shown to be 393 nm. In this article, using the same methods, the λmax values of RH1Cl, RH2Cl, SWS2Cl, and LWSCl pigments were determined to be 502, 503, 448, and 559 nm, respectively. The pigeon is also known for its UV vision, detecting light at 320–380 nm. Being the only pigments that absorb light below 400 nm, the SWS1Cl pigments must mediate its UV vision. We also determined that a nonretinal PCl pigment in the pineal gland of the pigeon has a λmax value at 481 nm.
Long Inverted Repeats Are an At-Risk Motif for Recombination in Mammalian Cells
Authors: Waldman Alan S , Tran Hiep , Goldsmith Edie C , Resnick Michael A 
Published: April 2021

Abstract
Certain DNA sequence motifs and structures can promote genomic instability. We have explored instability induced in mouse cells by long inverted repeats (LIRs). A cassette was constructed containing a herpes simplex virus thymidine kinase (tk) gene into which was inserted an LIR composed of two inverted copies of a 1.1-kb yeast URA3 gene sequence separated by a 200-bp spacer sequence. The tk gene was introduced into the genome of mouse Ltk− fibroblasts either by itself or in conjunction with a closely linked tk gene that was disrupted by an 8-bp XhoI linker insertion; rates of intrachromosomal homologous recombination between the markers were determined. Recombination between the two tk alleles was stimulated 5-fold by the LIR, as compared to a long direct repeat (LDR) insert, resulting in nearly 10−5 events per cell per generation. Of the tk+ segregants recovered from LIR-containing cell lines, 14% arose from gene conversions that eliminated the LIR, as compared to 3% of the tk+ segregants from LDR cell lines, corresponding to a &gt;20-fold increase in deletions at the LIR hotspot. Thus, an LIR, which is a common motif in mammalian genomes, is at risk for the stimulation of homologous recombination and possibly other genetic rearrangements.
Population Models of Genomic Imprinting. I. Differential Viability in the Sexes and the Analogy With Genetic Dominance
Authors: Anderson Richard J E , Spencer Hamish G 
Published: April 2021

Abstract
Many single-locus, two-allele selection models of genomic imprinting have been shown to reduce formally to one-locus Mendelian models with a modified parameter for genetic dominance. One exception is the model where selection at the imprinted locus affects the sexes differently. We present two models of maternal inactivation with differential viability in the sexes, one with complete inactivation, and the other with a partial penetrance for inactivation. We show that, provided dominance relations at the imprintable locus are the same in both sexes, a globally stable polymorphism exists for a range of viabilities that is independent of the penetrance of imprinting. The conditions for a polymorphism are the same as in previous models with differential viability in the sexes but without imprinting and in a model of the paternal X-inactivation system in marsupials. The model with incomplete inactivation is used to illustrate the analogy between imprinting and dominance by comparing equilibrium bifurcation plots for fixed values of dominance and penetrance. We also derive a single expression for the dominance parameter that leaves the frequency and stability of equilibria unchanged for all levels of inactivation. Although an imprinting model with sex differences does not formally reduce to a nonimprinting scheme, close theoretical parallels clearly exist.
A Comparison of Multilocus Clines Maintained by Environmental Adaptation or by Selection Against Hybrids
Authors: Kruuk L E B , Baird S J E , Gale K S , Barton N H 
Published: April 2021

AbstractThere has recently been considerable debate over the relative importance of selection against hybrids (“endogenous” selection) vs. adaptation to different environments (“exogenous”) in maintaining stable hybrid zones and hence in speciation. Single-locus models of endogenous and exogenous viability selection generate clines of similar shape, but the comparison has not been extended to multilocus systems, which are both quantitatively and qualitatively very different from the single-locus case. Here we develop an analytical multilocus model of differential adaptation across an environmental transition and compare it to previous heterozygote disadvantage models. We show that the shape of clines generated by exogenous selection is indistinguishable from that generated by endogenous selection. A stochastic simulation model is used to test the robustness of the analytical description to the effects of drift and strong selection, and confirms the prediction that pairwise linkage disequilibria are predominantly generated by migration. However, although analytical predictions for the width of clines maintained by heterozygote disadvantage fit well with the simulation results, those for environmental adaptation are consistently too narrow; reasons for the discrepancy are discussed. There is a smooth transition between a system in which a set of loci effectively act independently of each other and one in which they act as a single nonrecombining unit.
Effect of DNA Sequence Divergence on Homologous Recombination as Analyzed by a Random-Walk Model
Authors: Fujitani Youhei , Kobayashi Ichizo 
Published: April 2021

Abstract
A point connecting a pair of homologous regions of DNA duplexes moves along the homology in a reaction intermediate of the homologous recombination. Formulating this movement as a random walk, we were previously successful at explaining the dependence of the recombination frequency on the homology length. Recently, the dependence of the recombination frequency on the DNA sequence divergence in the homologous region was investigated experimentally; if the methyl-directed mismatch repair (MMR) system is active, the logarithm of the recombination frequency decreases very rapidly with an increase of the divergence in a low-divergence regime. Beyond this regime, the logarithm decreases slowly and linearly with the divergence. This “very rapid drop-off” is not observed when the MMR system is defective. In this article, we show that our random-walk model can explain these data in a straightforward way. When a connecting point encounters a diverged base pair, it is assumed to be destroyed with a probability that depends on the level of MMR activity.
Genetic Analysis of Transcription-Associated Mutation in Saccharomyces cerevisiae
Authors: Morey Natalie J , Greene Christopher N , Jinks-Robertson Sue 
Published: April 2021

Abstract
High levels of transcription are associated with elevated mutation rates in yeast, a phenomenon referred to as transcription-associated mutation (TAM). The transcription-associated increase in mutation rates was previously shown to be partially dependent on the Rev3p translesion bypass pathway, thus implicating DNA damage in TAM. In this study, we use reversion of a pGAL-driven lys2ΔBgl allele to further examine the genetic requirements of TAM. We find that TAM is increased by disruption of the nucleotide excision repair or recombination pathways. In contrast, elimination of base excision repair components has only modest effects on TAM. In addition to the genetic studies, the lys2ΔBgl reversion spectra of repair-proficient low and high transcription strains were obtained. In the low transcription spectrum, most of the frameshift events correspond to deletions of AT base pairs whereas in the high transcription strain, deletions of GC base pairs predominate. These results are discussed in terms of transcription and its role in DNA damage and repair.
Do-It-Yourself Statistics: A Computer-Assisted Likelihood Approach to Analysis of Data From Genetic Crosses
Authors: Robbins Leonard G 
Published: April 2021

Abstract
Graduate school programs in genetics have become so full that courses in statistics have often been eliminated. In addition, typical introductory statistics courses for the “statistics user” rather than the nascent statistician are laden with methods for analysis of measured variables while genetic data are most often discrete numbers. These courses are often seen by students and genetics professors alike as largely irrelevant cookbook courses. The powerful methods of likelihood analysis, although commonly employed in human genetics, are much less often used in other areas of genetics, even though current computational tools make this approach readily accessible. This article introduces the MLIKELY.PAS computer program and the logic of do-it-yourself maximum-likelihood statistics. The program itself, course materials, and expanded discussions of some examples that are only summarized here are available at http://www.unisi.it/ricerca/dip/bio_evol/sitomlikely/mlikely.html.
Expression of the Saccharomyces cerevisiae Gene YME1 in the Petite-Negative Yeast Schizosaccharomyces pombe Converts It to Petite-Positive
Authors: Kominsky Douglas J , Thorsness Peter E 
Published: April 2021

Abstract
Organisms that can grow without mitochondrial DNA are referred to as “petite-positive” and those that are inviable in the absence of mitochondrial DNA are termed “petite-negative.” The petite-positive yeast Saccharomyces cerevisiae can be converted to a petite-negative yeast by inactivation of Yme1p, an ATP- and metal-dependent protease associated with the inner mitochondrial membrane. Suppression of this yme1 phenotype can occur by virtue of dominant mutations in the α- and γ-subunits of mitochondrial ATP synthase. These mutations are similar or identical to those occurring in the same subunits of the same enzyme that converts the petite-negative yeast Kluyveromyces lactis to petite-positive. Expression of YME1 in the petite-negative yeast Schizosaccharomyces pombe converts this yeast to petite-positive. No sequence closely related to YME1 was found by DNA-blot hybridization to S. pombe or K. lactis genomic DNA, and no antigenically related proteins were found in mitochondrial extracts of S. pombe probed with antisera directed against Yme1p. Mutations that block the formation of the F1 component of mitochondrial ATP synthase are also petite-negative. Thus, the F1 complex has an essential activity in cells lacking mitochondrial DNA and Yme1p can mediate that activity, even in heterologous systems.
Linkage Analysis of Sex Determination in Bracon sp. Near hebetor (Hymenoptera: Braconidae)
Authors: Holloway Alisha K , Strand Michael R , Black William C , Antolin Michael F 
Published: April 2021

Abstract
To test whether sex determination in the parasitic wasp Bracon sp. near hebetor (Hymenoptera: Braconidae) is based upon a single locus or multiple loci, a linkage map was constructed using random amplified polymorphic DNA (RAPD) markers. The map includes 71 RAPD markers and one phenotypic marker, blonde. Sex was scored in a manner consistent with segregation of a single “sex locus” under complementary sex determination (CSD), which is common in haplodiploid Hymenoptera. Under haplodiploidy, males arise from unfertilized haploid eggs and females develop from fertilized diploid eggs. With CSD, females are heterozygous at the sex locus; diploids that are homozygous at the sex locus become diploid males, which are usually inviable or sterile. Ten linkage groups were formed at a minimum LOD of 3.0, with one small linkage group that included the sex locus. To locate other putative quantitative trait loci (QTL) for sex determination, sex was also treated as a binary threshold character. Several QTL were found after conducting permutation tests on the data, including one on linkage group I that corresponds to the major sex locus. One other QTL of smaller effect had a segregation pattern opposite to that expected under CSD, while another putative QTL showed a female-specific pattern consistent with either a sex-differentiating gene or a sex-specific deleterious mutation. Comparisons are made between this study and the indepth studies on sex determination and sex differentiation in the closely related B. hebetor.
Genotypic Stability, Segregation and Selection in Heteroplasmic Human Cell Lines Containing np 3243 Mutant mtDNA
Authors: Lehtinen Sanna K , Hance Nicole , El Meziane Abdellatif , Juhola M Katariina , Juhola K Martti I , Karhu Ritva , Spelbrink Johannes N , Holt Ian J , Jacobs Howard T 
Published: April 2021

Abstract
The mitochondrial genotype of heteroplasmic human cell lines containing the pathological np 3243 mtDNA mutation, plus or minus its suppressor at np 12300, has been followed over long periods in culture. Cell lines containing various different proportions of mutant mtDNA remained generally at a consistent, average heteroplasmy value over at least 30 wk of culture in nonselective media and exhibited minimal mitotic segregation, with a segregation number comparable with mtDNA copy number (≥1000). Growth in selective medium of cells at 99% np 3243 mutant mtDNA did, however, allow the isolation of clones with lower levels of the mutation, against a background of massive cell death. As a rare event, cell lines exhibited a sudden and dramatic diversification of heteroplasmy levels, accompanied by a shift in the average heteroplasmy level over a short period (&lt;8 wk), indicating selection. One such episode was associated with a gain of chromosome 9. Analysis of respiratory phenotype and mitochondrial genotype of cell clones from such cultures revealed that stable heteroplasmy values were generally reestablished within a few weeks, in a reproducible but clone-specific fashion. This occurred independently of any straightforward phenotypic selection at the individual cell-clone level. Our findings are consistent with several alternate views of mtDNA organization in mammalian cells. One model that is supported by our data is that mtDNA is found in nucleoids containing many copies of the genome, which can themselves be heteroplasmic, and which are faithfully replicated. We interpret diversification and shifts of heteroplasmy level as resulting from a reorganization of such nucleoids, under nuclear genetic control. Abrupt remodeling of nucleoids in vivo would have major implications for understanding the developmental consequences of heteroplasmy, including mitochondrial disease phenotype and progression.
Extensive Genetic Interactions Between PRP8 and PRP17/CDC40, Two Yeast Genes Involved in Pre-mRNA Splicing and Cell Cycle Progression
Authors: Ben-Yehuda Sigal , Russell Caroline S , Dix Ian , Beggs Jean D , Kupiec Martin 
Published: April 2021

Abstract
Biochemical and genetic experiments have shown that the PRP17 gene of the yeast Saccharomyces cerevisiae encodes a protein that plays a role during the second catalytic step of the splicing reaction. It was found recently that PRP17 is identical to the cell division cycle CDC40 gene. cdc40 mutants arrest at the restrictive temperature after the completion of DNA replication. Although the PRP17/CDC40 gene product is essential only at elevated temperatures, splicing intermediates accumulate in prp17 mutants even at the permissive temperature. In this report we describe extensive genetic interactions between PRP17/CDC40 and the PRP8 gene. PRP8 encodes a highly conserved U5 snRNP protein required for spliceosome assembly and for both catalytic steps of the splicing reaction. We show that mutations in the PRP8 gene are able to suppress the temperature-sensitive growth phenotype and the splicing defect conferred by the absence of the Prp17 protein. In addition, these mutations are capable of suppressing certain alterations in the conserved PyAG trinucleotide at the 3′ splice junction, as detected by an ACT1-CUP1 splicing reporter system. Moreover, other PRP8 alleles exhibit synthetic lethality with the absence of Prp17p and show a reduced ability to splice an intron bearing an altered 3′ splice junction. On the basis of these findings, we propose a model for the mode of interaction between the Prp8 and Prp17 proteins during the second catalytic step of the splicing reaction.
The Product of the DNA Damage-Inducible Gene of Saccharomyces cerevisiae, DIN7, Specifically Functions in Mitochondria
Authors: Fikus Marta U , Mieczkowski Piotr A , Koprowski Piotr , Rytka Joanna , Śledziewska-Gójska Ewa , Cieśla Zygmunt 
Published: April 2021

Abstract
We reported previously that the product of the DNA damage-inducible gene of Saccharomyces cerevisiae, DIN7, belongs to a family of proteins that are involved in DNA repair and replication. The family includes S. cerevisiae proteins Rad2p and its human homolog XPGC, Rad27p and its mammalian homolog FEN-1, and Exonuclease I (Exo I). Here, we report that Din7p specifically affects metabolism of mitochondrial DNA (mtDNA). We have found that dun1 strains, defective in the transcriptional activation of the DNA damage-inducible genes RNR1, RNR2, and RNR3, exhibit an increased frequency in the formation of the mitochondrial petite (ρ−) mutants. This high frequency of petites arising in the dun1 strains is significantly reduced by the din7::URA3 allele. On the other hand, overproduction of Din7p from the DIN7 gene placed under control of the GAL1 promoter dramatically increases the frequency of petite formation and the frequency of mitochondrial mutations conferring resistance to erythromycin (Er). The frequencies of chromosomal mutations conferring resistance to canavanine (Canr) or adenine prototrophy (Ade+) are not affected by enhanced synthesis of Din7p. Experiments using Din7p fused to the green fluorescent protein (GFP) and cell fractionation experiments indicate that the protein is located in mitochondria. A possible mechanism that may be responsible for the decreased stability of the mitochondrial genome in S. cerevisiae cells with elevated levels of Din7p is discussed.
A Yeast Heterogeneous Nuclear Ribonucleoprotein Complex Associated With RNA Polymerase II
Authors: Conrad Nicholas K , Wilson Scott M , Steinmetz Eric J , Patturajan Meera , Brow David A , Swanson Maurice S , Corden Jeffry L 
Published: April 2021

Abstract
Recent evidence suggests a role for the carboxyl-terminal domain (CTD) of the largest subunit of RNA polymerase II (pol II) in pre-mRNA processing. The yeast NRD1 gene encodes an essential RNA-binding protein that shares homology with mammalian CTD-binding proteins and is thought to regulate mRNA abundance by binding to a specific cis-acting element. The present work demonstrates genetic and physical interactions among Nrd1p, the pol II CTD, Nab3p, and the CTD kinase CTDK-I. Previous studies have shown that Nrd1p associates with the CTD of pol II in yeast two-hybrid assays via its CTD-interaction domain (CID). We show that nrd1 temperature-sensitive alleles are synthetically lethal with truncation of the CTD to 9 or 10 repeats. Nab3p, a yeast hnRNP, is a high-copy suppressor of some nrd1 temperature-sensitive alleles, interacts with Nrd1p in a yeast two-hybrid assay, and coimmunoprecipitates with Nrd1p. Temperature-sensitive alleles of NAB3 are suppressed by deletion of CTK1, a kinase that has been shown to phosphorylate the CTD and increase elongation efficiency in vitro. This set of genetic and physical interactions suggests a role for yeast RNA-binding proteins in transcriptional regulation.