bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural Requirements for the Tissue-Specific and Tissue-General Functions of the Caenorhabditis elegans Epidermal Growth Factor LIN-3
Authors: Liu Jing , Tzou Phoebe , Hill Russell J , Sternberg Paul W 
Published: April 2021

Abstract
Caenorhabditis elegans lin-3 encodes a homolog of the epidermal growth factor (EGF) family of growth factors. LIN-3 is the inductive signal for hermaphrodite vulval differentiation, and it is required for animal viability, hermaphrodite fertility, and the specification of anterior cell fates in the male B cell lineage. We describe the cloning of a lin-3 homolog from C. briggsae, sequence comparison of C. elegans lin-3 with C. briggsae lin-3, and the determination of molecular lesions in alleles of C. elegans lin-3, including three new alleles. We also analyzed the severity of phenotypes caused by the new and existing alleles of lin-3. Correlation of mutant phenotypes and their molecular lesions, as well as sequence comparison between two species, reveal that the EGF motif and the N-terminal portion of the cytoplasmic domain are important for the functions of LIN-3 in all tissues, while the C-terminal portion of the cytoplasmic domain is involved in the tissue-specific functions of lin-3. We discuss how the structure of lin-3 contributes to its functions in multiple developmental processes.
Molecular Evolution of Two Linked Genes, Est-6 and Sod, in Drosophila melanogaster
Authors: Balakirev Evgeniy S , Balakirev Elena I , Rodríguez-Trelles Francisco , Ayala Francisco J 
Published: April 2021

Abstract
We have obtained 15 sequences of Est-6 from a natural population of Drosophila melanogaster to test whether linkage disequilibrium exists between Est-6 and the closely linked Sod, and whether natural selection may be involved. An early experiment with allozymes had shown linkage disequilibrium between these two loci, while none was detected between other gene pairs. The Sod sequences for the same 15 haplotypes were obtained previously. The two genes exhibit similar levels of nucleotide polymorphism, but the patterns are different. In Est-6, there are nine amino acid replacement polymorphisms, one of which accounts for the S-F allozyme polymorphism. In Sod, there is only one replacement polymorphism, which corresponds to the S-F allozyme polymorphism. The transversion/transition ratio is more than five times larger in Sod than in Est-6. At the nucleotide level, the S and F alleles of Est-6 make up two allele families that are quite different from each other, while there is relatively little variation within each of them. There are also two families of alleles in Sod, one consisting of a subset of F alleles, and the other consisting of another subset of F alleles, designed F(A), plus all the S alleles. The Sod F(A) and S alleles are completely or nearly identical in nucleotide sequence, except for the replacement mutation that accounts for the allozyme difference. The two allele families have independent evolutionary histories in the two genes. There are traces of statistically significant linkage disequilibrium between the two genes that, we suggest, may have arisen as a consequence of selection favoring one particular sequence at each locus.
Melanoma Loss-of-Function Mutants in Xiphophorus Caused by Xmrk-Oncogene Deletion and Gene Disruption by a Transposable Element
Authors: Schartl Manfred , Hornung Ute , Gutbrod Heidrun , Volff Jean-Nicolas , Wittbrodt Joachim 
Published: April 2021

Abstract
The overexpression of the Xmrk oncogene (ONC-Xmrk) in pigment cells of certain Xiphophorus hybrids has been found to be the primary change that results in the formation of malignant melanoma. Spontaneous mutant stocks have been isolated that have lost the ability to induce tumor formation when crossed with Xiphophorus helleri. Two of these loss-of-function mutants were analyzed for genetic defects in ONC-Xmrk's. In the lof-1 mutant a novel transposable element, TX-1, has jumped into ONC-Xmrk, leading to a disruption of the gene and a truncated protein product lacking the carboxyterminal domain of the receptor tyrosine kinase. TX-1 is obviously an active LTR-containing retrotransposon in Xiphophorus that was not found in other fish species outside the family Poeciliidae. Surprisingly, it does not encode any protein, suggesting the existence of a helper function for this retroelement. In the lof-2 mutant the entire ONC-Xmrk gene was found to be deleted. These data show that ONC-Xmrk is indeed the tumor-inducing gene of Xiphophorus and thus the critical constituent of the tumor (Tu) locus.
Suppressors of Systemin Signaling Identify Genes in the Tomato Wound Response Pathway
Authors: Howe Gregg A , Ryan Clarence A 
Published: April 2021

Abstract
In tomato plants, systemic induction of defense genes in response to herbivory or mechanical wounding is regulated by an 18-amino-acid peptide signal called systemin. Transgenic plants that overexpress prosystemin, the systemin precursor, from a 35S::prosystemin (35S::prosys) transgene exhibit constitutive expression of wound-inducible defense proteins including proteinase inhibitors and polyphenol oxidase. To study further the role of (pro)systemin in the wound response pathway, we isolated and characterized mutations that suppress 35S::prosys-mediated phenotypes. Ten recessive, extragenic suppressors were identified. Two of these define new alleles of def-1, a previously identified mutation that blocks both wound- and systemin-induced gene expression and renders plants susceptible to herbivory. The remaining mutants defined four loci designated Spr-1, Spr-2, Spr-3, and Spr-4 (for Suppressed in 35S::prosystemin-mediated responses). spr-3 and spr-4 mutants were not significantly affected in their response to either systemin or mechanical wounding. In contrast, spr-1 and spr-2 plants lacked systemic wound responses and were insensitive to systemin. These results confirm the function of (pro)systemin in the transduction of systemic wound signals and further establish that wounding, systemin, and 35S::prosys induce defensive gene expression through a common signaling pathway defined by at least three genes (Def-1, Spr-1, and Spr-2).
Mutational Analysis of the [Het-s] Prion Analog of Podospora anserina: A Short N-Terminal Peptide Allows Prion Propagation
Authors: Coustou Virginie , Deleu Carole , Saupe Sven J , Bégueret Joël 
Published: April 2021

Abstract
The het-s locus is one of nine known het (heterokaryon incompatibility) loci of the fungus Podospora anserina. This locus exists as two wild-type alleles, het-s and het-S, which encode 289 amino acid proteins differing at 13 amino acid positions. The het-s and het-S alleles are incompatible as their coexpression in the same cytoplasm causes a characteristic cell death reaction. We have proposed that the HET-s protein is a prion analog. Strains of the het-s genotype exist in two phenotypic states, the neutral [Het-s*] and the active [Het-s] phenotype. The [Het-s] phenotype is infectious and is transmitted to [Het-s*] strains through cytoplasmic contact. het-s and het-S were associated in a single haploid nucleus to generate a self-incompatible strain that displays a restricted and abnormal growth. In the present article we report the molecular characterization of a collection of mutants that restore the ability of this self-incompatible strain to grow. We also describe the functional analysis of a series of deletion constructs and site-directed mutants. Together, these analyses define positions critical for reactivity and allele specificity. We show that a 112-amino-acid-long N-terminal peptide of HET-s retains [Het-s] activity. Moreover, expression of a mutant het-s allele truncated at position 26 is sufficient to allow propagation of the [Het-s] prion analog.
A Screen for Identifying Genes Interacting With Armadillo, the Drosophila Homolog of β-Catenin
Authors: Greaves Sarah , Sanson Bénédicte , White Phoebe , Vincent Jean-Paul 
Published: April 2021

Abstract
Drosophila Armadillo is a multifunctional protein implicated in both cell adhesion, as a catenin, and cell signaling, as part of the Wingless signal transduction pathway. We have generated viable fly stocks with alterations in the level of Armadillo available for signaling. Flies from one stock overexpress Armadillo and, as a result, have increased vein material and bristles in the wings. Flies from the other stock have reduced cytoplasmic Armadillo following overexpression of the intracellular domain of DE-cadherin. These flies display a wing-notching phenotype typical of wingless mutations. Both misexpression phenotypes can be dominantly modified by removing one copy of genes known to encode members of the wingless pathway. Here we describe the identification of further mutations that dominantly modify the Armadillo misexpression phenotypes. These mutations are in genes encoding three different functions: establishment and maintenance of adherens junctions, cell cycle control, and Egfr signaling.
Evolution of the Proportions of Two Sigma Viral Types in Experimental Populations of Drosophila melanogaster in the Absence of the Allele That Is Restrictive of Viral Multiplication
Authors: Fleuriet Annie 
Published: April 2021

Abstract
A minority of flies in natural populations of Drosophila melanogaster are endemically infected by a rhabdovirus, sigma. The virus is vertically transmitted through male and female gametes. Two alleles of a fly locus, the ref(2)P locus, are present as a polymorphism in all populations: O permissive, and P restrictive for viral multiplication and transmission. Two viral types are known, Type I, which is very sensitive to the P allele, and Type II, which is more resistant. Previous observations have shown that, in presence of the P allele, viral Type II is selected for, in both natural and experimental populations. The aim of the present study was to determine whether, in the absence of P, Type I is selected for, or whether the two types are equivalent. For this purpose, experimental populations deprived of the P allele and differing in the initial proportions of the two viral types were established. After several generations, and despite a possible bias toward Type I, the frequencies of Type I and Type II clones differed in the various populations, depending on their initial values. These findings do not rule out selective advantage of viral Type I in the absence of P, but suggest that, if any, this advantage is in no way comparable to that displayed by viral Type II in the presence of P.
Molecular Genetic Analysis of Drosophila eyes absent Mutants Reveals an Eye Enhancer Element
Authors: Zimmerman John E , Bui Quang T , Liu Haixi , Bonini Nancy M 
Published: April 2021

Abstract
The eyes absent (eya) gene is critical for normal eye development in Drosophila and is highly conserved to vertebrates. To define regions of the gene critical for eye function, we have defined the mutations in the four viable eya alleles. Two of these mutations are eye specific and undergo transvection with other mutations in the gene. These were found to be deletion mutations that remove regulatory sequence critical for eye cell expression of the gene. Two other viable alleles cause a reduced eye phenotype and affect the function of the gene in additional tissues, such as the ocelli. These mutations were found to be insertion mutations of different transposable elements within the 5′ UTR of the transcript. Detailed analysis of one of these revealed that the transposable element has become subject to regulation by eye enhancer sequences of the eya gene, disrupting normal expression of EYA in the eye. More extended analysis of the deletion region in the eye-specific alleles indicated that the deleted region defines an enhancer that activates gene expression in eye progenitor cells. This enhancer is responsive to ectopic expression of the eyeless gene. This analysis has defined a critical regulatory region required for proper eye expression of the eya gene.
Genetic Architecture of a Morphological Shape Difference Between Two Drosophila Species
Authors: Zeng Zhao-Bang , Liu Jianjun , Stam Lynn F , Kao Chen-Hung , Mercer John M , Laurie Cathy C 
Published: April 2021

Abstract
The size and shape of the posterior lobe of the male genital arch differs dramatically between Drosophila simulans and D. mauritiana. This difference can be quantified with a morphometric descriptor (PC1) based on elliptical Fourier and principal components analyses. The genetic basis of the interspecific difference in PC1 was investigated by the application of quantitative trait locus (QTL) mapping procedures to segregating backcross populations. The parental difference (35 environmental standard deviations) and the heritability of PC1 in backcross populations (&gt;90%) are both very large. The use of multiple interval mapping gives evidence for 19 different QTL. The greatest additive effect estimate accounts for 11.4% of the parental difference but could represent multiple closely linked QTL. Dominance parameter estimates vary among loci from essentially no dominance to complete dominance, and mauritiana alleles tend to be dominant over simulans alleles. Epistasis appears to be relatively unimportant as a source of variation. All but one of the additive effect estimates have the same sign, which means that one species has nearly all plus alleles and the other nearly all minus alleles. This result is unexpected under many evolutionary scenarios and suggests a history of strong directional selection acting on the posterior lobe.
Ancient Allelism at the Cytosolic Chaperonin-α-Encoding Gene of the Zebrafish
Authors: Takami Kimitaka , Figueroa Felipe , Mayer Werner E , Klein Jan 
Published: April 2021

AbstractThe T-complex protein 1, TCP1, gene codes for the CCT-α subunit of the group II chaperonins. The gene was first described in the house mouse, in which it is closely linked to the T locus at a distance of ~11 cM from the Mhc. In the zebrafish, Danio rerio, in which the T homolog is linked to the class I Mhc loci, the TCP1 locus segregates independently of both the T and the Mhc loci. Despite its conservation between species, the zebrafish TCP1 locus is highly polymorphic. In a sample of 15 individuals and the screening of a cDNA library, 12 different alleles were found, and some of the allelic pairs were found to differ by up to nine nucleotides in a 275-bp-long stretch of sequence. The substitutions occur in both translated and untranslated regions, but in the former they occur predominantly at synonymous codon sites. Phylogenetically, the alleles fall into two groups distinguished also by the presence or absence of a 10-bp insertion/deletion in the 3′ untranslated region. The two groups may have diverged as long as 3.5 mya, and the polymorphic differences may have accumulated by genetic drift in geographically isolated populations.
Sex-of-Offspring-Specific Transmission Ratio Distortion on Mouse Chromosome X
Authors: de la Casa-Esperón Elena , de Villena Fernando Pardo-Manuel , Verner Andrei E , Briscoe Tammi L , Malette Jan Michel , Rosa Michelle , Jin Wen-Hui , Sapienza Carmen 
Published: April 2021

Abstract
During our study of the DDK syndrome, we observed sex ratio distortion in favor of males among the offspring of F1 backcrosses between the C57BL/6 and DDK strains. We also observed significant and reproducible transmission ratio distortion in favor of the inheritance of DDK alleles at loci on chromosome X among female offspring but not among male offspring in (C57BL/6 × DDK)F1 × C57BL/6 and (C57BL/6-Pgk1a × DDK)F1 × C57BL/6 backcrosses. The observed transmission ratio distortion is maximum at DXMit210 in the central region of chromosome X and decreases progressively at proximal and distal loci, in a manner consistent with the predictions of a single distorted locus model. DXMit210 is closely linked to two distortion-controlling loci (Dcsx1 and Dcsx2) described previously in interspecific backcrosses. Our analysis suggests that the female-offspring-specific transmission ratio distortion we observe is likely to be the result of the death of embryos of particular genotypic combinations. In addition, we confirm the previous suggestion that the transmission ratio distortion observed on chromosome X in interspecific backcrosses is also the result of loss of embryos.
Synthetic Genetic Interactions With Temperature-Sensitive Clathrin in Saccharomyces cerevisiae: Roles for Synaptojanin-Like Inp53p and Dynamin-Related Vps1p in Clathrin-Dependent Protein Sorting at the trans-Golgi Network
Authors: Bensen Eric S , Costaguta Giancarlo , Payne Gregory S 
Published: April 2021

Abstract
Clathrin is involved in selective protein transport at the Golgi apparatus and the plasma membrane. To further understand the molecular mechanisms underlying clathrin-mediated protein transport pathways, we initiated a genetic screen for mutations that display synthetic growth defects when combined with a temperature-sensitive allele of the clathrin heavy chain gene (chc1-521) in Saccharomyces cerevisiae. Mutations, when present in cells with wild-type clathrin, were analyzed for effects on mating pheromone α-factor precursor maturation and sorting of the vacuolar protein carboxypeptidase Y as measures of protein sorting at the yeast trans-Golgi network (TGN) compartment. By these criteria, two classes of mutants were obtained, those with and those without defects in protein sorting at the TGN. One mutant with unaltered protein sorting at the TGN contains a mutation in PTC1, a type 2c serine/threonine phosphatase with widespread influences. The collection of mutants displaying TGN sorting defects includes members with mutations in previously identified vacuolar protein sorting genes (VPS), including the dynamin family member VPS1. Striking genetic interactions were observed by combining temperature-sensitive alleles of CHC1 and VPS1, supporting the model that Vps1p is involved in clathrin-mediated vesicle formation at the TGN. Also in the spectrum of mutants with TGN sorting defects are isolates with mutations in the following: RIC1, encoding a product originally proposed to participate in ribosome biogenesis; LUV1, encoding a product potentially involved in vacuole and microtubule organization; and INP53, encoding a synaptojanin-like inositol polyphosphate 5-phosphatase. Disruption of INP53, but not the related INP51 and INP52 genes, resulted in α-factor maturation defects and exacerbated α-factor maturation defects when combined with chc1-521. Our findings implicate a wide variety of proteins in clathrin-dependent processes and provide evidence for the selective involvement of Inp53p in clathrin-mediated protein sorting at the TGN.
Telomere Structure Regulates the Heritability of Repressed Subtelomeric Chromatin in Saccharomyces cerevisiae
Authors: Park Yangsuk , Lustig Arthur J 
Published: April 2021

Abstract
Telomeres, the protein-DNA structures present at the termini of linear chromosomes, are capable of conferring a reversible repression of Pol II- and Pol III-transcribed genes positioned in adjacent subtelomeric regions. This phenomenon, termed telomeric silencing, is likely to be the consequence of a more global telomere position effect at the level of chromatin structure. To understand the role of telomere structure in this position effect, we have developed an assay to distinguish between the heritability of transcriptionally repressed and derepressed states in yeast. We have previously demonstrated that an elongated telomeric tract leads to hyperrepression of telomere-adjacent genes. We show here that the predominant effect of elongated telomeres is to increase the inheritance of the repressed state in cis. Interestingly, the presence of elongated telomeres overcomes the partial requirement of yCAF-1 in silencing. We propose that the formation of a specific telomeric structure is necessary for the heritability of repressed subtelomeric chromatin.
Suppressed Recombination and a Pairing Anomaly on the Mating-Type Chromosome of Neurospora tetrasperma
Authors: Gallegos Alena , Jacobson David J , Raju Namboori B , Skupski Marian P , Natvig Donald O 
Published: April 2021

Abstract
Neurospora crassa and related heterothallic ascomycetes produce eight homokaryotic self-sterile ascospores per ascus. In contrast, asci of N. tetrasperma contain four self-fertile ascospores each with nuclei of both mating types (matA and mata). The self-fertile ascospores of N. tetrasperma result from first-division segregation of mating type and nuclear spindle overlap at the second meiotic division and at a subsequent mitotic division. Recently, Merino et al. presented population-genetic evidence that crossing over is suppressed on the mating-type chromosome of N. tetrasperma, thereby preventing second-division segregation of mating type and the formation of self-sterile ascospores. The present study experimentally confirmed suppressed crossing over for a large segment of the mating-type chromosome by examining segregation of markers in crosses of wild strains. Surprisingly, our study also revealed a region on the far left arm where recombination is obligatory. In cytological studies, we demonstrated that suppressed recombination correlates with an extensive unpaired region at pachytene. Taken together, these results suggest an unpaired region adjacent to one or more paired regions, analogous to the nonpairing and pseudoautosomal regions of animal sex chromosomes. The observed pairing and obligate crossover likely reflect mechanisms to ensure chromosome disjunction.
EAT-20, a Novel Transmembrane Protein With EGF Motifs, Is Required for Efficient Feeding in Caenorhabditis elegans
Authors: Shibata Yukimasa , Fujii Takashi , Dent Joseph A , Fujisawa Hajime , Takagi Shin 
Published: April 2021

Abstract
The pharynx of Caenorhabditis elegans is a neuromuscular organ responsible for feeding, concentrating food by its pumping movement. A class of mutants, the eat mutants, are defective in this behavior. We have identified a novel eat gene, eat-20, encoding a unique transmembrane protein with three EGF motifs. Staining with a specific polyclonal antibody reveals that EAT-20 is expressed predominantly in the pharyngeal muscles and a subset of neurons. Some hypodermal cells also express EAT-20. eat-20 mutant animals are starved, have smaller brood sizes, and have prolonged egg-laying periods. The starvation apparently results from pharyngeal pumping defects, including a reduced pumping rate and “slippery pumping,” in which the contents of the pharynx sometimes move rostrally. However, electrical activity of eat-20 mutants appears normal by electropharyngeogram.
Mutational Analysis of a Histone Deacetylase in Drosophila melanogaster: Missense Mutations Suppress Gene Silencing Associated With Position Effect Variegation
Authors: Mottus Randy , Sobel Richard E , Grigliatti Thomas A 
Published: April 2021

Abstract
For many years it has been noted that there is a correlation between acetylation of histones and an increase in transcriptional activity. One prediction, based on this correlation, is that hypomorphic or null mutations in histone deacetylase genes should lead to increased levels of histone acetylation and result in increased levels of transcription. It was therefore surprising when it was reported, in both yeast and fruit flies, that mutations that reduced or eliminated a histone deacetylase resulted in transcriptional silencing of genes subject to telomeric and heterochromatic position effect variegation (PEV). Here we report the first mutational analysis of a histone deacetylase in a multicellular eukaryote by examining six new mutations in HDAC1 of Drosophila melanogaster. We observed a suite of phenotypes accompanying the mutations consistent with the notion that HDAC1 acts as a global transcriptional regulator. However, in contrast to recent findings, here we report that specific missense mutations in the structural gene of HDAC1 suppress the silencing of genes subject to PEV. We propose that the missense mutations reported here are acting as antimorphic mutations that “poison” the deacetylase complex and propose a model that accounts for the various phenotypes associated with lesions in the deacetylase locus.