bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Immune System and Response Genes, and Novel Mutations Causing Melanotic Tumor Formation in Drosophila melanogaster
Authors: Rodriguez Antony , Zhou Zhijian , Tang My Lien , Meller Steve , Chen Jiewen , Bellen Hugo , Kimbrell Deborah A 
Published: January 2021

Abstract
We are using Drosophila as a model system for analysis of immunity and tumor formation and have conducted two types of screens using enhancer detector strains to find genes related to these processes: genes expressed in the immune system (type A, hemocytes, lymph glands and fat body) and genes increased in expression by bacterial infection (type B). For type A, tissue-specific reporter gene activity was determined. For type B, a variation of enhancer detection was devised in which β-galactosidase is assayed spectrophotometrically with and without bacterial infection. Because of immune system involvement in melanotic tumor formation, a third type was hypothesized to be found among types A and B: genes that, when mutated, have a melanotic tumor phenotype. Enhancer detector strains (2800) were screened for type A, 900 for B, and 11 retained for further analysis. Complementation tests, cytological mapping, P-element mobilization, and determination of lethal phase and mutant phenotype have identified six novel genes, Dorothy, wizard, toto, Viking, Thor and dappled, and one previously identified gene, Collagen IV. All are associated with reporter gene expression in at least one immune system tissue. Thor has increased expression upon infection. Mutations of wizard and dappled have a melanotic tumor phenotype.
An Integrated Genetic Map of the African Human Malaria Vector Mosquito, Anopheles gambiae
Authors: Zheng Liangbiao , Benedict Mark Q , Cornel Anton J , Collins Frank H , Kafatos Fotis C 
Published: January 2021

Abstract
We present a genetic map based on microsatellite polymorphisms for the African human malaria vector, Anopheles gambiae. Polymorphisms in laboratory strains were detected for 89% of the tested microsatellite markers. Genotyping was performed for individual mosquitoes from 13 backcross families that included 679 progeny. Three linkage groups were identified, corresponding to the three chromosomes. We added 22 new markers to the existing X chromosome map, for a total of 46 microsatellite markers spanning a distance of 48.9 cM. The second chromosome has 57 and the third 28 microsatellite markers spanning a distance of 72.4 and 93.7 cM, respectively. The overall average distance between markers is 1.6 cM (or 1.1, 1.2, and 3.2 cM for the X, second, and third chromosomes, respectively). In addition to the 131 microsatellite markers, the current map also includes a biochemical selectable marker, Dieldrin resistance (Dl), on the second chromosome and five visible markers, pink-eye (p) and white (w) on the X, collarless (c) and lunate (lu) on the second, and red-eye (r) on the third. The cytogenetic locations on the nurse cell polytene chromosomes have been determined for 47 markers, making this map an integrated tool for cytogenetic, genetic, and molecular analysis.
Bacteriophage T4 Mutants Hypersensitive to an Antitumor Agent That Induces Topoisomerase-DNA Cleavage Complexes
Authors: Woodworth Denise L , Kreuzer Kenneth N 
Published: January 2021

Abstract
Many antitumor agents and antibiotics affect cells by interacting with type II topoisomerases, stabilizing a covalent enzyme-DNA complex. A pathway of recombination can apparently repair this DNA damage. In this study, transposon mutagenesis was used to identify possible components of the repair pathway in bacteriophage T4. Substantial increases in sensitivity to the antitumor agent m-AMSA [4′-(9-acridinylamino)methanesulfon-m-anisidide] were found with transposon insertion mutations that inactivate any of six T4-encoded proteins: UvsY (DNA synaptase accessory protein), UvsW (unknown function), Rnh (RNase H and 5′ to 3′ DNA exonuclease), α-gt (α-glucosyl transferase), gp47.1 (uncharacterized), and NrdB (β subunit of ribonucleotide reductase). The role of the rnh gene in drug sensitivity was further characterized. First, an in-frame rnh deletion mutation was constructed and analyzed, providing evidence that the absence of Rnh protein causes hypersensitivity to m-AMSA. Second, the m-AMSA sensitivity of the rnh-deletion mutant was shown to require a drug-sensitive T4 topoisomerase. Third, analysis of double mutants suggested that uvsW and rnh mutations impair a common step in the recombinational repair pathway for m-AMSA-induced damage. Finally, the rnh-deletion mutant was found to be hypersensitive to UV, implicating Rnh in recombinational repair of UV-induced damage.
Isolation and Analysis of the arg-13 Gene of Neurospora crassa
Authors: Liu Qiuyun , Dunlap Jay C 
Published: January 2021

Abstract
Mutations in arg-13 result in slow growth in minimal medium and can suppress mutations in carbamyl phosphate synthase-aspartate carbamyl transferase within the pyrimidine pathway; the exact biochemical function of the gene product is unknown. To understand the role of arg-13 in arginine metabolism, cosmids rescuing growth in arg-13 mutants were cloned and mapped to the position of arg-13 on LG IR. Northern analysis showed the arg-13 message to contain ~2100 nt, although a 1.4kb genomic fragment truncated at the 5′ and 3′ ends of the gene encodes a shortened transcript that can rescue arg-13 function. Expression of mRNA arising from the mutant arg-13 gene is induced by arginine starvation, although wild type (arg-13 +) is not derepressed in minimal medium. The sequence of the arg-13 gene shows ARGl3 to be a member of the mitochondrial carrier superfamily with three repeats of a ~100-amino acid domain, six putative membrane spanning regions, and three copies of the mitochondrial carrier consensus pattern. This information plus available and new nutritional data are consistent with the hypothesis that arg-13 encodes a mitochondrial basic amino acid carrier whose existence was predicted based upon previous physiological, nutritional and biochemical data.
Genetic Analysis of the Roles of daf28 and age-1 in Regulating Caenorhabditis elegans Dauer Formation
Authors: Malone Elizabeth A , Inoue Takao , Thomas James H 
Published: January 2021

Abstract
Based on environmental cues, the nervous system of Caenorhabditis ekgans regulates formation of the dauer larva, an alternative larval form specialized for long-term survival under harsh conditions. Mutations that cause constitutive or defective dauer formation (Daf-c or Daf-d) have been identified and the genes ordered in a branched pathway. Most Daf-c mutations also affect recovery from the dauer stage. The semidominant mutation daf-28(sa191) is Daf-c but has no apparent effect on dauer recovery. We use this unique aspect of daf28(sal91) to characterize the effects of several Daf-d and synthetic Daf-c mutations on dauer recovery. We present double mutant analysis that indicates that daf-28(saI91) acts at a novel point downstream in the genetic pathway for dauer formation. We also show that daf-28(sa191) causes a modest increase (12-13%) in life span. The phenotypes and genetic interactions of daf-28(sa191) are most similar to those of daf-2 and daf-23 mutations, which also cause a dramatic increase in life span. We present mapping and complementation data that suggest that daf-23 is the same gene as age-I, identified previously by mutations that extend life span. We find that age-l alleles are also Daf-c at 27°.
Comparing Mutational Variabilities
Authors: Houle David , Morikawa Bob , Lynch Michael 
Published: January 2021

Abstract
We have reviewed the available data on VM, the amount of genetic variation in phenotypic traits produced each generation by mutation. We use these data to make several qualitative tests of the mutation-selection balance hypothesis for the maintenance of genetic variance (MSB). To compare VM values, we use three dimensionless quantities: mutational heritability, the mutational coefficient of variation, CVM; and the ratio of the standing genetic variance to VM, VG/VM. Since genetic coefficients of variation for life history traits are larger than those for morphological traits, we predict that under MSB, life history traits should also have larger CVM. This is confirmed; life history traits have a median CVM value more than six times higher than that for morphological traits. VG/VM approximates the persistence time of mutations under MSB in an infinite population. In order for MSB to hold, VG/VM must be small, substantially less than 1000, and life history traits should have smaller values than morphological traits. VG/VM averages about 50 generations for life history traits and 100 generations for morphological traits. These observations are all consistent with the predictions of a mutation-selection balance model.
The Maternal Nude1 Protein of Drosophila Has Two Distinct Roles Important for Embryogenesis
Authors: Hong Charles C , Hashimoto Carl 
Published: January 2021

Abstract
The nudel gene is maternally required to define dorsoventral polarity of the Drosophila embryo. It encodes an unusual mosaic protein with a protease domain that may trigger the protease cascade required for ventral development. We describe phenotypic and molecular analyses of nudel mutations that provide further insight into nudel protein function. Surprisingly, nudel mutations primarily cause either dorsalized embryos in which dorsal cell fates are expanded over ventral and lateral cell fates or fragile eggs that fail to develop beyond early embryonic stages. The nudel protein is therefore required not only for embryonic dorsoventral polarity but also for structural integrity of the egg. Complementation and antagonistic interactions between nudel alleles suggest that the nudel protein is functionally modular and that protein-protein interactions are important for nudel protein function. Three nudel mutations that produce dorsalized embryos map to the protease domain of nudel, suggesting that this domain is specifically required for defining embryonic dorsoventral polarity. Finally, certain combinations of nudel alleles simultaneously produce completely dorsalized and normal embryos yet very few embryos of intermediate mutant phenotypes. The unusual biphasic distribution of phenotypes may indicate that nudel activity above a threshold is required to generate embryonic dorsoventral polarity.
Quantitative Genetics of Transgenic Mice: Components of Phenotypic Variation in Body Weights and Weight Gains
Authors: Clutter A C , Pomp D , Murray J D 
Published: January 2021

Abstract
Transgenic mice possessing an ovine growth hormone gene were used to study the effects of elevated growth hormone on quantitative genetic variation. Males hemizygous for the transgene were mated to wild-type females to produce half- and full-sib families in which approximately half the progeny were transgenic and half were wild type. Analyses of body weights at 3–10 weeks, and weight gains from 3 to 6, and 6 to 10 weeks produced estimates of the proportion of total variance due to additive genetic effects (h2) and common litter effects (c2), and the genetic correlation between transgenic and wild-type expression of each trait. At 10 weeks, body weight of transgenics exceeded that of wild types by 26 and 49% in males and females, respectively. Estimated genetic variances in the transgenic group were significantly greater than zero for body weights at most ages and for both measurements of gain. Common litter effects accounted for a similar proportion of variation in the wild-type and transgenic groups. Additive genetic correlations between wild-type and transgenic expression of body weights tended to decline with age, indicating that a partially different array of genes may have begun to affect body weight in the transgenic group.
The Use of Multiple Markers in a Bayesian Method for Mapping Quantitative Trait Loci
Authors: Uimari Pekka , Thaller Georg , Hoeschele Ina 
Published: January 2021

Abstract
Information on multiple linked genetic markers was used in a Bayesian method for the statistical mapping of quantitative trait loci (QTL). Bayesian parameter estimation and hypothesis testing were implemented via Markov chain Monte Carlo algorithms. Variables sampled were the augmented data (marker-QTL genotypes, polygenic effects), an indicator variable for linkage or nonlinkage, and the parameters. The parameter vector included allele frequencies at the markers and the QTL, map distances of the markers and the QTL, QTL substitution effect, and polygenic and residual variances. The criterion for QTL detection was the marginal posterior probability of a QTL being located on the chromosome carrying the markers, The method was evaluated empirically by analyzing simulated granddaughter designs consisting of 2000 sons, 20 related sires, and their ancestors.
Comparison of the Structure and Expression of odd-skipped and Two Related Genes That Encode a New Family of Zinc Finger Proteins in Drosophila
Authors: Hart Marilyn C , Wang Lei , Coulter Douglas E 
Published: January 2021

Abstract
The odd-skipped (odd) gene, which was identified on the basis of a pair-rule segmentation phenotype in mutant embryos, is initially expressed in the Drosophila embryo in seven pair-rule stripes, but later exhibits a segment polarity-like pattern for which no phenotypic correlate is apparent. We have molecularly characterized two embryonically expressed odd-cognate genes, sob and bowel (bowl), that encode proteins with highly conserved C2H2 zinc fingers. While the Sob and Bowl proteins each contain five tandem fingers, the Odd protein lacks a fifth (C-terminal) finger and is also less conserved among the four common fingers. Reminiscent of many segmentation gene paralogues, the closely linked odd and sob genes are expressed during embryogenesis in similar striped patterns; in contrast, the less-tightly linked bowlgene is expressed in a distinctly different pattern at the termini of the early embryo. Although our results indicate that odd and sob are more likely than bowl to share overlapping developmental roles, some functional divergence between the Odd and Sob proteins is suggested by the absence of homology outside the zinc fingers, and also by amino acid substitutions in the Odd zinc fingers at positions that appear to be constrained in Sob and Bowl.
Cloning of the Drosophila melanogaster Meiotic Recombination Gene mei-218: A Genetic and Molecular Analysis of Interval 15E
Authors: McKim Kim S , Dahmus Jeffrey B , Hawley R Scott 
Published: January 2021

Abstract
The mei-218 gene product is required for both meiotic crossing over and for the production of recombination nodules, suggesting that these organelles are required for meiotic exchange. In this study the null phenotype of mei-218 was defined through the analysis of three preexisting and five new alleles. Consistent with previous studies, in homozygous mi-218 mutants meiotic crossing over is reduced to &lt;10% of normal levels. A molecular analysis of mei-218 was initiated with the isolation and mapping of lethal mutations and genome rearrangements in the region containing mi-218, polytene interval 15E on the X chromosome. This high resolution genetic map was aligned with a physical map constructed from cosmid and P1 clones by genetically mapping restriction fragment length polymorphisms and localizing rearrangement breakpoints. Within a region of 65 kb, we have identified seven transcription units, including mei-218 and the Minute(l)l5D gene, which encodes ribosomal protein S5. The mei-218 mutant phenotype has been rescued by germline transformation with both a genomic fragment and a cDNA under the control of the hsp83 promoter. The mei-218 gene is predicted to produce an 1186 amino acid protein that has no significant similarities to any known proteins.
The Effects of Natural Hybridization on the Regulation of Doubly Uniparental mtDNA Inheritance in Blue Mussels (Mytilus spp.)
Authors: Ramon Paul D , Secor Carol L , Hilbish Thomas J 
Published: January 2021

Abstract
Blue mussels in the Mythilus edulis species complex have a doubly uniparental mode of mtDNA inheritance with separate maternal and paternal mtDNA lineages. Female mussels inherit their mtDNA solely from their mother, while males inherit mtDNA from both parents. In the male gonad the paternal mtDNA is preferentially replicated so that only paternal mtDNA is transmitted from fathers to sons. Hybridization is common among differentiated blue mussel taxa; whenever it involves M. trossulus, doubly uniparental mtDNA inheritance is disrupted. We have found high frequencies of males without and females with paternal mtDNA among hybrid mussels produced by interspecific matings between M. galloprovincialis and M. trossulus. In contrast, hybridization between M. galloprovincialis and M. edulis does not affect doubly uniparental inheritance, indicating a difference in the divergence of the mechanisms regulating mtDNA inheritance among the three blue mussel taxa. Our data indicate a high frequency of disrupted mtDNA transmission in F1 hybrids and suggest that two separate mechanisms, one regulating the transmission of paternal mtDNA to males and another inhibiting the establishment of paternal mtDNAin females, act to regulate doubly uniparental inheritance. We propose a model for the regulation of doubly uniparental inheritance that is consistent with these observations.
A Test of the Double-Strand Break Repair Model for Meiotic Recombination in Saccharomyces cerevisiae
Authors: Gilbertson Larry A , Stahl Franklin W 
Published: January 2021

Abstract
We tested predictions of the double-strand break repair (DSBR) model for meiotic recombination by examining the segregation patterns of small palindromic insertions, which frequently escape mismatch repair when in heteroduplex DNA. The palindromes flanked a well characterized DSB site at the ARC4 locus. The “canonical” DSBR model, in which only 5′ ends are degraded and resolution of the four-stranded intermediate is by Holliday junction resolvase, predicts that hDNA will frequently occur on both participating chromatids in a single event. Tetrads reflecting this configuration of hDNA were rare. In addition, a class of tetrads not predicted by the canonical DSBR model was identified. This class represented events that produced hDNA in a “trans” configuration, on opposite strands of the same duplex on the two sides of the DSB site. Whereas most classes of convertant tetrads had typical frequencies of associated crossovers, tetrads with trans hDNA were parental for flanking markers. Modified versions of the DSBR model, including one that uses a topoisomerase to resolve the canonical DSBR intermediate, are supported by these data.
A Genetic Linkage Map of the Male Goat Genome
Authors: Vaiman Daniel , Schibler Laurent , Bourgeois Florence , Oustry Anne , Amigues Yves , Cribiu Edmond P 
Published: January 2021

Abstract
This paper presents a first genetic linkage map of the goat genome. Primers derived from the flanking sequences of 612 bovine, ovine and goat microsatellite markers were gathered and tested for amplification with goat DNA under standardized PCR conditions. This screen made it possible to choose a set of 55 polymorphic markers that can be used in the three species and to define a panel of 223 microsatellites suitable for the goat. Twelve half-sib paternal goat families were then used to build a linkage map of the goat genome. The linkage analysis made it possible to construct a meiotic map covering 2300 cM, i.e., &gt;SO% of the total estimated length of the goat genome. Moreover, eight cosmids containing microsatellites were mapped by fluorescence in situ hybridization in goat and sheep. Together with 11 microsatellite-containing cosmids previously mapped in cattle (and supposing conservation of the banding pattern between this species and the goat) and data from the sheep map, these results made the orientation of 15 linkage groups possible. Furthermore, 12 coding sequences were mapped either genetically or physically, providing useful data for comparative mapping.
Both Loss-of-Function and Gain-of-Function Mutations in snf Define a Role for snRNP Proteins in Regulating Sex-lethal Pre-mRNA Splicing in Drosophila Development
Authors: Salz Helen K , Flickinger Thomas W 
Published: January 2021

Abstract
The Drosophila snf gene encodes a protein with functional homology to the mammalian UlA and U2B″ snRNP proteins. Studies, based on the analysis of three viable alleles, have suggested a role for snf in establishing the female-specific splicing pattern of the sex determination switch gene, Sex-lethal. Here, we show that the non-sex-specific lethal null allele is required for female sex determination, arguing against the formal possibility that the viable alleles disrupt a function unrelated to snf's wild-type function. Moreover, we find snf is required for normal cell growth and/or survival, as expected for a protein involved in a cell-vital process such as RNA splicing. We also show that of the three viable alleles only one, snfJA2, is a partial loss-of-function mutation. The other two viable alleles, snf1621 and snfe8H, encode antimorphic proteins. We find the antimorphic proteins are mislocalized and correlate their mislocalization with their molecular lesions and mutant phenotypes. Finally, we provide genetic evidence that the antimorphic alleles interfere with the autoregulatory splicing function of the Sex-lethal protein. Based on these studies we suggest a model in which the snRNP protein, Snf, functions with Sex-lethal to block recognition of the regulated male-specific exon.
In Vivo Analysis Reveals That the Interdomain Region of the Yeast Proliferating Cell Nuclear Antigen Is Important for DNA Replication and DNA Repair
Authors: Amin Neelam S , Holm Connie 
Published: January 2021

Abstract
To identify the regions of the proliferating cell nuclear antigen (PCNA) that are important for function in vivo, we used random mutagenesis to isolate 10 cold-sensitive (Cs−) and 31 methyl methanesulfonate-sensitive (Mmss) mutations of the PCNA gene (POL30) in Saccharomyces cerevisiae. Unlike the Mmss mutations, the CsC mutations are strikingly clustered in the interdomain region of the three-dimensional PCNA monomer structure. At the restrictive temperature, the Cs− pol30 mutants undergo a RAD9 dependent arrest as large-budded cells with a 2c DNA content. Defects in DNA synthesis are suggested by a significant delay in the progression of synchronized pol30 cells through S phase at the restrictive temperature. DNA repair defects are revealed by the observation that Cs− pol30 mutants are very sensitive to the alkylating agent MMS and mildly sensitive to ultraviolet radiation, although they are not sensitive to gamma radiation. Finally, analysis of the chromosomal DNA in pol30 cells by velocity sedimentation gradients shows that pol30 cells accumulate single-stranded DNA breaks at the restrictive temperature. Thus, our results show that PCNA plays an essential role in both DNA replication and DNA repair in vivo.