bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temperature-Sensitive Mutations in the Saccharomyces cerevisiae MRT4, GRC5, SLA2 and THS1 Genes Result in Defects in mRNA Turnover
Authors: Zuk Dorit , Belk Jonathan P , Jacobson Allan 
Published: April 2021

Abstract
In a screen for factors involved in mRNA turnover, four temperature-sensitive yeast strains (ts1189, ts942, ts817, and ts1100) exhibited defects in the decay of several mRNAs. Complementation of the growth and mRNA decay defects, and genetic experiments, revealed that ts1189 is mutated in the previously unknown MRT4 gene, ts942 is mutated in GRC5 (encoding the L9 ribosomal protein), ts817 contains a mutation in SLA2 (encoding a membrane protein), and ts1100 contains a mutation in THS1 (encoding the threonyl-tRNA synthetase). Three of the four mutants (mrt4, grc5, and sla2) were not defective in protein synthesis, suggesting that these strains contain mutations in factors that may play a specific role in mRNA decay. The mRNA stabilization observed in the ths1 strain, however, could be due to the significant drop in translation observed in this mutant at 37°. While the three interesting mutants appear to encode novel mRNA decay factors, at least one could be linked to a previously characterized mRNA decay pathway. The growth and mRNA decay defects of ts942 (grc5) cells were suppressed by overexpression of the NMD3 gene, encoding a protein shown to participate in a two-hybrid interaction with the nonsense-mediated decay protein Upf1p.
Genetic Dissection of X-Linked Interspecific Hybrid Placental Dysplasia in Congenic Mouse Strains
Authors: Hemberger Myriam C , Pearsall Robert S , Zechner Ulrich , Orth Annie , Otto Sabine , Rüschendorf Franz , Fundele Reinald , Elliott Rosemary 
Published: April 2021

Abstract
Interspecific hybridization in the genus Mus results in male sterility and X-linked placental dysplasia. We have generated several congenic laboratory mouse lines (Mus musculus) in which different parts of the maternal X chromosome were derived from M. spretus. A strict positive correlation between placental weight and length of the M. spretus-derived part of the X chromosome was shown. Detailed analysis was carried out with one congenic strain that retained a M. spretus interval between 12.0 and 30.74 cM. This strain consistently produced hyperplastic placentas that exhibited an average weight increase of 180% over the weight of control placentas. In derived subcongenic strains, however, increased placental weight could no longer be observed. Morphometric analysis of these placentas revealed persistence of abnormal morphology. Fully developed placental hyperplasia could be reconstituted by recombination of proximal and central M. spretus intervals with an intervening M. musculus region. These results may suggest that placental dysplasia of interspecific mouse hybrids is caused by multiple loci clustered on the X chromosome that act synergistically. Alternatively, it is possible that changes in chromatin structure in interspecific hybrids that influence gene expression are dependent on the length of the alien chromosome.
The Age of Nonsynonymous and Synonymous Mutations in Animal mtDNA and Implications for the Mildly Deleterious Theory
Authors: Nielsen Rasmus , Weinreich Daniel M 
Published: April 2021

AbstractMcDonald/Kreitman tests performed on animal mtDNA consistently reveal significant deviations from strict neutrality in the direction of an excess number of polymorphic nonsynonymous sites, which is consistent with purifying selection acting on nonsynonymous sites. We show that under models of recurrent neutral and deleterious mutations, the mean age of segregating neutral mutations is greater than the mean age of segregating selected mutations, even in the absence of recombination. We develop a test of the hypothesis that the mean age of segregating synonymous mutations equals the mean age of segregating nonsynonymous mutations in a sample of DNA sequences. The power of this age-of-mutation test and the power of the McDonald/Kreitman test are explored by computer simulations. We apply the new test to 25 previously published mitochondrial data sets and find weak evidence for selection against nonsynonymous mutations.
A Random Model Approach to Mapping Quantitative Trait Loci for Complex Binary Traits in Outbred Populations
Authors: Yi Nengjun , Xu Shizhong 
Published: April 2021

Abstract
Mapping quantitative trait loci (QTL) for complex binary traits is more challenging than for normally distributed traits due to the nonlinear relationship between the observed phenotype and unobservable genetic effects, especially when the mapping population contains multiple outbred families. Because the number of alleles of a QTL depends on the number of founders in an outbred population, it is more appropriate to treat the effect of each allele as a random variable so that a single variance rather than individual allelic effects is estimated and tested. Such a method is called the random model approach. In this study, we develop the random model approach of QTL mapping for binary traits in outbred populations. An EM-algorithm with a Fisher-scoring algorithm embedded in each E-step is adopted here to estimate the genetic variances. A simple Monte Carlo integration technique is used here to calculate the likelihood-ratio test statistic. For the first time we show that QTL of complex binary traits in an outbred population can be scanned along a chromosome for their positions, estimated for their explained variances, and tested for their statistical significance. Application of the method is illustrated using a set of simulated data.
Multiple Chromosomes in Bacteria: The Yin and Yang of trp Gene Localization in Rhodobacter sphaeroides 2.4.1
Authors: Mackenzie Chris , Simmons Adrian E , Kaplan Samuel 
Published: April 2021

Abstract
The existence of multiple chromosomes in bacteria has been known for some time. Yet the extent of functional solidarity between different chromosomes remains unknown. To examine this question, we have surveyed the well-described genes of the tryptophan biosynthetic pathway in the multichromosomal photosynthetic eubacterium Rhodobacter sphaeroides 2.4.1. The genome of this organism was mutagenized using Tn5, and strains that were auxotrophic for tryptophan (Trp-) were isolated. Pulsed-field gel mapping indicated that Tn5 insertions in both the large (3 Mb CI) and the small (0.9 Mb CII) chromosomes created a Trp- phenotype. Sequencing the DNA flanking the sites of the Tn5 insertions indicated that the genes trpE-yibQ-trpGDC were at a locus on CI, while genes trpF-aroR-trpB were at locus on CII. Unexpectedly, trpA was not found downstream of trpB. Instead, it was placed on the CI physical map at a locus 1.23 Mb away from trpE-yibQ-trpGDC. To relate the context of the R. sphaeroides trp genes to those of other bacteria, the DNA regions surrounding the trp genes on both chromosomes were sequenced. Of particular significance was the finding that rpsA1, which encodes ribosomal protein S1, and cmkA, which encodes cytidylate monophosphate kinase, were on CII. These genes are considered essential for translation and chromosome replication, respectively. Southern blotting suggested that the trp genes and rpsA1 exist in single copy within the genome. To date, this topological organization of the trp “operon” is unique within a bacterial genome. When taken with the finding that CII encodes essential housekeeping functions, the overall impression is one of close regulatory and functional integration between these chromosomes.
A Core Activity Associated with the N Terminus of the Yeast RAD52 Protein Is Revealed by RAD51 Overexpression Suppression of C-Terminal rad52 Truncation Alleles
Authors: Asleson Erin N , Okagaki Ron J , Livingston Dennis M 
Published: April 2021

Abstract
C-terminal rad52 truncation and internal deletion mutants were characterized for their ability to repair MMS-induced double-strand breaks and to produce viable spores during meiosis. The rad52-Δ251 allele, encoding the N-terminal 251 amino acids of the predicted 504-amino-acid polypeptide, supports partial activity for both functions. Furthermore, RAD51 overexpression completely suppresses the MMS sensitivity of a rad52-Δ251 mutant. The absence of the C terminus in the truncated protein makes it likely that suppression occurs by bypassing the C-terminal functions of Rad52p. RAD51 overexpression does not suppress the low level of spore viability that the rad52-Δ251 allele causes and only partially suppresses the defect in rad52 alleles encoding the N-terminal 292 or 327 amino acids. The results of this study also show that intragenic complementation between rad52 alleles is governed by a complex relationship that depends heavily on the two alleles involved and their relative dosage. In heteroallelic rad52 diploids, the rad52-Δ251 allele does not complement rad52 missense mutations altering residues 61 or 64 in the N terminus. However, complementation is achieved with each of these missense alleles when the rad52-Δ251 allele is overexpressed. Complementation also occurs between rad52-Δ327 and an internal deletion allele missing residues 210 through 327. We suggest that the first 251 amino acids of Rad52p constitute a core domain that provides critical RAD52 activities.
Characterization of Seven Genes Affecting Caenorhabditis elegans Hindgut Development
Authors: Chamberlin Helen M , Brown Keith B , Sternberg Paul W , Thomas James H 
Published: April 2021

Abstract
We have identified and characterized 12 mutations in seven genes that affect the development of the Caenorhabditis elegans hindgut. We find that the mutations can disrupt the postembryonic development of the male-specific blast cells within the hindgut, the hindgut morphology in both males and hermaphrodites, and in some cases, the expression of a hindgut marker in hermaphrodite animals. Mutations in several of the genes also affect viability. On the basis of their mutant phenotypes, we propose that the genes fall into four distinct classes: (1) egl-5 is required for regional identity of the tail; (2) sem-4 is required for a variety of ectodermal and mesodermal cell types, including cells in the hindgut; (3) two genes, lin-49 and lin-59, affect development of many cells, including hindgut; and (4) three genes, mab-9, egl-38, and lin-48, are required for patterning fates within the hindgut, making certain hindgut cells different from others. We also describe a new allele of the Pax gene egl-38 that is temperature sensitive and affects the conserved β-hairpin of the EGL-38 paired domain. Our results suggest that a combination of different factors contribute to normal C. elegans hindgut development.
Structure and Regulation of the Salivary Gland Secretion Protein Gene Sgs-1 of Drosophila melanogaster
Authors: Roth Günther E , Wattler Sigrid , Bornschein Hartmut , Lehmann Michael , Korge Günter 
Published: April 2021

Abstract
The Drosophila melanogaster gene Sgs-1 belongs to the secretion protein genes, which are coordinately expressed in salivary glands of third instar larvae. Earlier analysis had implied that Sgs-1 is located at the 25B2-3 puff. We cloned Sgs-1 from a YAC covering 25B2-3. Despite using a variety of vectors and Escherichia coli strains, subcloning from the YAC led to deletions within the Sgs-1 coding region. Analysis of clonable and unclonable sequences revealed that Sgs-1 mainly consists of 48-bp tandem repeats encoding a threonine-rich protein. The Sgs-1 inserts from single λ clones are heterogeneous in length, indicating that repeats are eliminated. By analyzing the expression of Sgs-1/lacZ fusions in transgenic flies, cis-regulatory elements of Sgs-1 were mapped to lie within 1 kb upstream of the transcriptional start site. Band shift assays revealed binding sites for the transcription factor fork head (FKH) and the factor secretion enhancer binding protein 3 (SEBP3) at positions that are functionally relevant. FKH and SEBP3 have been shown previously to be involved in the regulation of Sgs-3 and Sgs-4. Comparison of the levels of steady state RNA and of the transcription rates for Sgs-1 and Sgs-1/lacZ reporter genes indicates that Sgs-1 RNA is 100-fold more stable than Sgs-1/lacZ RNA. This has implications for the model of how Sgs transcripts accumulate in late third instar larvae.
The Genetic Analysis of Age-Dependent Traits: Modeling the Character Process
Authors: Pletcher Scott D , Geyer Charles J 
Published: April 2021

AbstractThe extension of classical quantitative genetics to deal with function-valued characters (also called infinite-dimensional characters) such as growth curves, mortality curves, and reaction norms, was begun by Kirkpatrick and co-workers. In this theory, the analogs of variance components for single traits are covariance functions for function-valued traits. In the approach presented here, we employ a variety of parametric models for covariance functions that have a number of desirable properties: the functions (1) are positive definite, (2) can be estimated using procedures like those currently used for single traits, (3) have a small number of parameters, and (4) allow simple hypotheses to be easily tested. The methods are illustrated using data from a large experiment that examined the effects of spontaneous mutations on age-specific mortality rates in Drosophila melanogaster. Our methods are shown to work better than a standard multivariate analysis, which assumes the character value at each age is a distinct character. Advantages over existing methods that model covariance functions as a series of orthogonal polynomials are discussed.
Uterine and Postnatal Maternal Effects in Mice Selected for Differential Rate of Early Development
Authors: Rhees Brian K , Ernst Cynthia A , Miao Christina H , Atchley William R 
Published: April 2021

AbstractA series of mouse lines was produced by long-term restricted index selection for divergent rate of growth during early and late postnatal development. The selection program was based on the following treatments: E+ and E- lines were selected to alter birth to 10-day weight gain while holding late gain for both lines constant and a control line was established via random selection. Using embryo transfer and crossfostering methodology, we partitioned postnatal growth for E+, E-, and C lines into progeny genetic, uterine maternal, and nurse maternal components. Selection for differential early growth resulted in correlated response in uterine and nurse maternal effects on body weights, with significant genetic-by-environment interactions. Significant uterine effects were also observed in tail length measurements. Direct uterine effects on body weight were relatively small and resulted in growth rate differences early in development. Nurse effects were large, resulting in modification of progeny growth trajectory especially during early postnatal development. Genetic-by-uterine interactions were large and demonstrate progeny-specific effects of the prenatal uterine environment.
Fission Yeast Mutants That Alleviate Transcriptional Silencing in Centromeric Flanking Repeats and Disrupt Chromosome Segregation
Authors: Ekwall Karl , Cranston Gwen , Allshire Robin C 
Published: April 2021

Abstract
In the fission yeast Schizosaccharomyces pombe genes are transcriptionally silenced when placed within centromeres, within or close to the silent mating-type loci or adjacent to telomeres. Factors required to maintain mating-type silencing also affect centromeric silencing and chromosome segregation. We isolated mutations that alleviate repression of marker genes in the inverted repeats flanking the central core of centromere I. Mutations csp1 to 13 (centromere: suppressor of position effect) defined 12 loci. Ten of the csp mutants have no effect on mat2/3 or telomere silencing. All csp mutants allow some expression of genes in the centromeric flanking repeat, but expression in the central core is undetectable. Consistent with defective centromere structure and function, chromosome loss rates are elevated in all csp mutants. Mutants csp1 to 6 are temperature-sensitive lethal and csp3 and csp6 cells are defective in mitosis at 36°. csp7 to 13 display a high incidence of lagging chromosomes on late anaphase spindles. Thus, by screening for mutations that disrupt silencing in the flanking region of a fission yeast centromere a novel collection of mutants affecting centromere architecture and chromosome segregation has been isolated.
The Saccharomyces cerevisiae RanGTP-Binding Protein Msn5p Is Involved in Different Signal Transduction Pathways
Authors: Alepuz Paula M , Matheos Dina , Cunningham Kyle W , Estruch Francisco 
Published: April 2021

Abstract
In eukaryotes, control of transcription by extracellular signals involves the translocation to the nucleus of at least one component of the signal transduction pathway. Transport through the nuclear envelope requires the activity of an import or export receptor that interacts with the small GTPase Ran. We have cloned the MSN5 gene of the yeast Saccharomyces cerevisiae that is postulated to encode one of these receptors. Msn5p belongs to a family of proteins with a conserved N-terminal sequence that acts as a RanGTP-binding domain. The results presented here provide genetic data supporting Msn5p involvement in several different signal transduction pathways. All of these pathways include changes in gene expression, and regulated nucleocytoplasmic redistribution of a component in response to external conditions has already been described in some of them. We have cloned MSN5 following two different strategies. Msn5p was constitutively localized in the nucleus. Phenotypic analysis of the msn5 mutant demonstrated that this protein participates in processes such as catabolite repression, calcium signaling, mating, and cell proliferation, as well as being involved in previously characterized phosphate utilization. Therefore, Msn5p could be a receptor for several proteins involved in different signaling pathways.
RNA Interference Can Target Pre-mRNA: Consequences for Gene Expression in a Caenorhabditis elegans Operon
Authors: Bosher Julia M , Dufourcq Pascale , Sookhareea Satis , Labouesse Michel 
Published: April 2021

Abstract
In nematodes, flies, trypanosomes, and planarians, introduction of double-stranded RNA results in sequence-specific inactivation of gene function, a process termed RNA interference (RNAi). We demonstrate that RNAi against the Caenorhabditis elegans gene lir-1, which is part of the lir-1/lin-26 operon, induced phenotypes very different from a newly isolated lir-1 null mutation. Specifically, lir-1(RNAi) induced embryonic lethality reminiscent of moderately strong lin-26 alleles, whereas the lir-1 null mutant was viable. We show that the lir-1(RNAi) phenotypes resulted from a severe loss of lin-26 gene expression. In addition, we found that RNAi directed against lir-1 or lin-26 introns induced similar phenotypes, so we conclude that lir-1(RNAi) targets the lir-1/lin-26 pre-mRNA. This provides direct evidence that RNA interference can prevent gene expression by targeting nuclear transcripts. Our results highlight that caution may be necessary when interpreting RNA interference without the benefit of mutant alleles.
Crossing Over During Caenorhabditis elegans Meiosis Requires a Conserved MutS-Based Pathway That Is Partially Dispensable in Budding Yeast
Authors: Zalevsky Jonathan , MacQueen Amy J , Duffy Joseph B , Kemphues Kenneth J , Villeneuve Anne M 
Published: April 2021

Abstract
Formation of crossovers between homologous chromosomes during Caenorhabditis elegans meiosis requires the him-14 gene. Loss of him-14 function severely reduces crossing over, resulting in lack of chiasmata between homologs and consequent missegregation. Cytological analysis showing that homologs are paired and aligned in him-14 pachytene nuclei, together with temperature-shift experiments showing that him-14 functions during the pachytene stage, indicate that him-14 is not needed to establish pairing or synapsis and likely has a more direct role in crossover formation. him-14 encodes a germline-specific member of the MutS family of DNA mismatch repair (MMR) proteins. him-14 has no apparent role in MMR, but like its Saccharomyces cerevisiae ortholog MSH4, has a specialized role in promoting crossing over during meiosis. Despite this conservation, worms and yeast differ significantly in their reliance on this pathway: whereas worms use this pathway to generate most, if not all, crossovers, yeast still form 30–50% of their normal number of crossovers when this pathway is absent. This differential reliance may reflect differential stability of crossover-competent recombination intermediates, or alternatively, the presence of two different pathways for crossover formation in yeast, only one of which predominates during nematode meiosis. We discuss a model in which HIM-14 promotes crossing over by interfering with Holliday junction branch migration.
DNA Polymorphism, Haplotype Structure and Balancing Selection in the Leavenworthia PgiC Locus
Authors: Filatov Dmitry A , Charlesworth Deborah 
Published: April 2021

AbstractA study of DNA polymorphism and divergence was conducted for the cytosolic phosphoglucose isomerase (PGI:E.C.5.3.1.9) gene of five species of the mustard genus Leavenworthia: Leavenworthia stylosa, L. alabamica, L. crassa, L. uniflora, and L. torulosa. Sequences of an internal 2.3-kb PgiC gene region spanning exons 6–16 were obtained from 14 L. stylosa plants from two natural populations and from one to several plants for each of the other species. The level of nucleotide polymorphism in L. stylosa PgiC gene was quite high (π = 0.051, θ = 0.052). Although recombination is estimated to be high in this locus, extensive haplotype structure was observed for the entire 2.3-kb region. The L. stylosa sequences fall into at least two groups, distinguished by the presence of several indels and nucleotide substitutions, and one of the three charge change nucleotide replacements within the region sequenced correlates with the haplotypes. The differences between the haplotypes are older than between the species, and the haplotypes are still segregating in at least two of five species studied. There is no evidence of recent or ancient population subdivision that could maintain distinct haplotypes. The age of the haplotypes and the results of Kelly's ZnS and Wall's B and Q tests with recombination suggest that the haplotypes are maintained due to balancing selection at or near this locus.
A Quantitative Model of the Relationship Between Phenotypic Variance and Heterozygosity at Marker Loci Under Partial Selfing
Authors: David Patrice 
Published: April 2021

AbstractNegative relationships between allozyme heterozygosity and morphological variance have often been observed and interpreted as evidence for increased developmental stability in heterozygotes. However, inbreeding can also generate such relationships by decreasing heterozygosity at neutral loci and redistributing genetic variance at the same time. I here provide a quantitative genetic model of this process by analogy with heterozygosity-fitness relationships. Inbreeding generates negative heterozygosity-variance relationships irrespective of the genetic architecture of the trait. This holds for fitness traits as well as neutral traits, the effect being stronger for fitness traits under directional dominance or overdominance. The order of magnitude of heterozygosity-variance regressions is compatible with empirical data even with very low inbreeding. Although developmental stability effects cannot be excluded, inbreeding is a parsimonious explanation that should be seriously considered to explain correlations between heterozygosity and both mean and variance of phenotypes in natural populations.