bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial and temporal patterns of lin-12 expression during C. elegans hermaphrodite development.
Authors: Wilkinson H A , Greenwald I 
Published: January 2021

Abstract
The lin-12 gene encodes a receptor that mediates certain cell-cell interactions during Caenorhabditis elegans development. We have examined the expression of a lin-12::lacZ reporter gene in individual cells during the development of C. elegans hermaphrodites. lin-12::lacZ is expressed in a discrete spatial and temporal pattern during development and teh lin-12::lacZ reporter gene will provide a useful marker for other studies, particularly of somatic gonadal and vulval development. In general, the cells that express lin-12:: lacZ correspond to cells whose fates are known to be altered in lin-12 mutants implying that restriction of lin-12 expression may be an important regulatory mechanism; the exceptions to this statement may reveal the cellular defects that underlie aspects of the lin-12 phenotype that have not been previously explained. For decisions that are not naturally variable, lin-12::lacZ expression does not appear to change before or upon commitment to a cell fate implying that in these cases postranscriptional regulation of lin-12 activity may control cell fate specification.
Localization of the nic-7, ac-29 and thi-10 genes within the mating-type locus of Chlamydomonas reinhardtii.
Authors: Ferris P J 
Published: January 2021

Abstract
The tight linkage observed between the mating-type (mt) locus of Chlamydomonas reinhardtii and three auxotrophic mutations--nic-7 (nicotinamide-requiring), ac-29 (acetate-requiring), and thi-10 (thiamine-requiring)--has led to the hypothesis that recombination is suppressed in the mt region. The physical location of these three genes has been established by transformation with sets of cloned DNA from the mt region. They lie to the left and right of the highly rearranged (R) domain of the mt locus, which has been proposed to be responsible for teh recombinational suppression in the region. The cloned nic-7+ and thi-10+ genes will be useful as selectable markers for cotransformation markers for cotransformation experiments.
The Drosophila meiotic recombination gene mei-9 encodes a homologue of the yeast excision repair protein Rad1.
Authors: Sekelsky J J , McKim K S , Chin G M , Hawley R S 
Published: January 2021

Abstract
Meiotic recombination and DNA repair are mediated by overlapping sets of genes. In the yeast Saccharomyces cerevisiae, many genes required to repair DNA double-strand breaks are also required for meiotic recombination. In contrast, mutations in genes required for nucleotide excision repair (NER) have no detectable effects on meiotic recombination in S. cerevisiae. The Drosophila melanogaster mei-9 gene is unique among known recombination genes in that it is required for both meiotic recombination and NER. We have analyzed the mei-9 gene at the molecular level and found that it encodes a homologue of the S. cerevisiae excision repair protein Rad1, the probable homologue of mammalian XPF/ERCC4. Hence, the predominant process of meiotic recombination in Drosophila proceeds through a pathway that is at least partially distinct from that of S. cerevisiae, in that it requires an NER protein. The biochemical properties of the Rad1 protein allow us to explain the observation that mei-9 mutants suppress reciprocal exchange without suppressing the frequency of gene conversion.
The genetic and molecular organization of the Dopa decarboxylase gene cluster of Drosophila melanogaster.
Authors: Stathakis D G , Pentz E S , Freeman M E , Kullman J , Hankins G R , Pearlson N J , Wright T R 
Published: January 2021

Abstract
We report the complete molecular organization of the Dopa decarboxylase gene cluster. Mutagenesis screens recovered 77 new Df(2L)TW130 recessive lethal mutations. These new alleles combined with 263 previously isolated mutations in the cluster to define 18 essential genes. In addition, seven new deficiencies were isolated and characterized. Deficiency mapping, restriction fragment length polymorphism (RFLP) analysis and P-element-mediated germline transformation experiments determined the gene order for all 18 loci. Genomic and cDNA restriction endonuclease mapping, Northern blot analysis and DNA sequencing provided information on exact gene location, mRNA size and transcriptional direction for most of these loci. In addition, this analysis identified two transcription units that had not previously been identified by extensive mutagenesis screening. Most of the loci are contained within two dense subclusters. We discuss the effectiveness of mutagens and strategies used in our screens, the variable mutability of loci within the genome of Drosophila melanogaster, the cytological and molecular organization of the Ddc gene cluster, the validity of the one band-one gene hypothesis and a possible purpose for the clustering of genes in the Ddc region.
Nondisjunction rates and abnormal embryonic development in a mouse cross between heterozygotes carrying a (7, 18) robertsonian translocation chromosome.
Authors: Oakey R J , Matteson P G , Litwin S , Tilghman S M , Nussbaum R L 
Published: January 2021

Abstract
Mice bearing Robertsonian translocation chromosomes frequently produce aneuploid gametes. They are therefore excellent tools for studying nondisjunction in mammals. Genotypic analysis of embryos from a mouse cross between two different strains of mice carrying a (7,18) Robertsonian chromosome enabled us to measure the rate of nondisjunction for chromosomes 7 and 18. Embryos (429) were harvested from 76 litters of mice and the parental origin of each chromosome 7 and 18 determined. Genotyping these embryos has allowed us to conclude the following: (1) there were 96 embryos in which at least one nondisjunction event had taken place; (2) the rate of maternal nondisjunction was greater than paternal nondisjunction for teh chromosomes sampled in these mice; (3) a bias against chromosome 7 and 18 nullisomic gametes was observed, reflected in a smaller than expected number of uniparental disomic embryos; (4) nondisjunction events did not seem to occur at random throughout the 76 mouse litters, but were clustered into fewer than would be expected cy chance; and (5) a deficiency of paternal chromosome 18 uniparental disomic embryos was observed along with a higher than normal rate of developmental retardation at 8.5 days post coitum, raising the possibility that this chromosome has at least one imprinted gene.
Mitochondrial portraits of human populations using median networks.
Authors: Bandelt H J , Forster P , Sykes B C , Richards M B 
Published: January 2021

Abstract
Analysis of variation in the hypervariable region of mitochondrial DNA (mtDNA) has emerged as an important tool for studying human evolution and migration. However, attempts to reconstruct optimal intraspecific mtDNA phylogenies frequently fail because parallel mutation events partly obscure the true evolutionary pathways. This makes it inadvisable to present a single phylogenetic tree at the expense of neglecting equally acceptable ones. As an alternative, we propose a novel network approach for portraying mtDNA relationships. For small sample sizes (&lt; approximately 50), an unmodified median network contains all most parsimonious trees, displays graphically the full information content of the sequence data, and can easily be generated by hand. For larger sample sizes, we reduce the complexity of the network by identifying parallelisms. This reduction procedure is guided by a compatibility argument and an additional source of phylogenetic information: the frequencies of the mitochondrial haplotypes. As a spin-off, our approach can also assist in identifying sequencing errors, which manifest themselves in implausible network substructures. We illustrate the advantages of our approach with several examples from existing data sets.
Host movement and the genetic structure of populations of parasitic nematodes.
Authors: Blouin M S , Yowell C A , Courtney C H , Dame J B 
Published: January 2021

Abstract
Mitochondrial DNA (mtDNA) sequence data were used to compare the population genetic structures of five species of parasitic nematodes from three different hosts: Ostertagia ostertagi and Haemonchus placei from cattle, H. contortus and Teladorsagia circumcincta from sheep, and Mazamastrongylus odocoilei from white-tailed deer. The parasites of sheep and cattle showed a pattern consistent with high gene flow among populations. The parasite of deer showed a pattern of substantial population subdivision and isolation by distance. It appears that host movement is an important determinant of population genetic structure in these nematodes. High gene flow in the parasites of livestock also indicates great opportunity for the spread of rare alleles that confer resistance to anthelmintic drugs. All species, including the parasite of deer, had unusually high within-population diversities (averages of 0.019-0.027 substitutions per site between pairs of individuals from the same population). Large effective population sizes (Ne), perhaps in combination with rapid mtDNA evolution, appear to be the most likely explanation for these high within-population diversities.
Two distinct temperature-sensitive alleles at the elav locus of Drosophila are suppressed nonsense mutations of the same tryptophan codon.
Authors: Samson M L , Lisbin M J , White K 
Published: January 2021

Abstract
The Drosophila gene elav encodes a 483-amino-acid-long nuclear RNA binding protein required for normal neuronal differentiation and maintenance. We molecularly analyzed the three known viable alleles of the gene, namely elavts1, elavFliJ1, and elavFliJ2, which manifest temperature-sensitive phenotypes. The modification of the elavFliJ1 allele corresponds to the change of glycine426 (GGA) into a glutamic acid (GAA). Surprisingly, elavts1 and elavFliJ2 were both found to have tryptophan419 (TGG) changed into two different stop codons, TAG and TGA, respectively. Unexpectedly, protein analysis from elavts1 and elavFliJ2 reveals not only the predicted 45-kD truncated ELAV protein due to translational truncation, but also a predominant full-size 50-kD ELAV protein, both at permissive and nonpermissive temperatures. The full-length protein present in elavts1 and elavFliJ2 can a priori be explained by one of several mechanisms leading to functional suppression of the nonsense mutation or by detection of a previously unrecognized ELAV isoform of similar size resulting from alternative splicing and unaffected by the stop codon. Experiments described in this article support the functional suppression of the nonsense mutation as the mechanism responsible for the full-length protein.
Evolutionary consequences of mutation and selection within an individual.
Authors: Otto S P , Orive M E 
Published: January 2021

Abstract
Whether in sexual or asexual organisms, selection among cell lineages during development is an effective way of eliminating deleterious mutations. Using a mathematical analysis, we find that relatively small differences in cell replication rates during development can translate into large differences in the proportion of mutant cells within the adult, especially when development involves a large number of cell divisions. Consequently, intraorganismal selection can substantially reduce the deleterious mutation rate observed among offspring as well as the mutation load within a population, because cells rather than individuals provide the selective "deaths" necessary to stem the tide of deleterious mutations. The reduction in mutation rate among offspring is more pronounced in organisms with plastic development than in those with structured development. It is also more pronounced in asexual organisms that produce multicellular rather than unicellular offspring. By effecting the mutation rate, intraorganismal selection may have broad evolutionary implications; as an example, we consider its influence on the evolution of ploidy levels, finding that cell-lineage selection is more effective in haploids and tends to favor their evolution.
vph6 mutants of Saccharomyces cerevisiae require calcineurin for growth and are defective in vacuolar H(+)-ATPase assembly.
Authors: Hemenway C S , Dolinski K , Cardenas M E , Hiller M A , Jones E W , Heitman J 
Published: January 2021

Abstract
We have characterized a Saccharomyces cerevisiae mutant strain that is hypersensitive to cyclosporin A (CsA) and FK506, immunosuppressants that inhibit calcineurin, a serine-threonine-specific phosphatase (PP2B). A single nuclear mutation, designated cev1 for calcineurin essential for viability, is responsible for the CsA-FK506-sensitive phenotype. The peptidyl-prolyl cis-trans isomerases cyclophilin A and FKBP12, respectively, mediate CsA and FK506 toxicity in the cev1 mutant strain. We demonstrate that cev1 is an allele of the VPH6 gene and that vph6 mutant strains fail to assemble the vacuolar H(+)-ATPase (V-ATPase). The VPH6 gene was mapped on chromosome VIII and is predicted to encode a 181-amino acid (21 kD) protein with no identity to other known proteins. We find that calcineurin is essential for viability in many mutant strains with defects in V-ATPase function or vacuolar acidification. In addition, we find that calcineurin modulates extracellular acidification in response to glucose, which we propose occurs via calcineurin regulation of the plasma membrane H(+)-ATPase PMA1. Taken together, our findings suggest calcineurin plays a general role in the regulation of cation transport and homeostasis.
Requirements for activity of the yeast mitotic recombination hotspot HOT1: RNA polymerase I and multiple cis-acting sequences.
Authors: Huang G S , Keil R L 
Published: January 2021

Abstract
When inserted at novel locations in the yeast genome, the Saccharomyces cerevisiae recombination hotspot HOT1 stimulates mitotic exchange in adjacent sequences. HOT1 is derived from the rDNA repeat unit, and the sequences required for the recombination-stimulatory activity closely correspond to the rDNA transcription enhancer and initiation site, suggesting there is an association between high levels of RNA polymerase I transcription and increased recombination. To directly test whether RNA polymerase I is essential for HOT1 activity, a subunit of RNA polymerase I was deleted in a strain in which rRNA is transcribed by RNA polymerase II. HOT1 is completely inactive in this strain. Deletion analysis and site-directed mutagenesis were used to further define the sequences within the rDNA enhancer required for HOT1 activity. These studies show that the enhancer contains at least four distinct regions that are required for hotspot activity. In most cases mutations in these regions also decrease transcription from this element, further confirming the association of recombination and transcription.
Molecular and genetic analysis of the toxic effect of RAP1 overexpression in yeast.
Authors: Freeman K , Gwadz M , Shore D 
Published: January 2021

Abstract
Rap1p is a context-dependent regulatory protein in yeast that functions as a transcriptional activator of many essential genes, including those encoding ribosomal proteins and glycolytic enzymes. Rap1p also participates in transcriptional silencing at HM mating-type loci and telomeres. Overexpression of RAP1 strongly inhibits cell growth, perhaps by interfering with essential transcriptional activation functions within the cell. Here we report a molecular and genetic analysis of the toxic effect of RAP1 overexpression. We show that toxicity does not require the previously defined Rap1p activation and silencing domains, but instead is dependent upon the DNA-binding domain and an adjacent region of unknown function. Point mutations were identified in the DNA-binding domain that relieve the toxic effect of overexpression. Two of these mutations can complement a RAP1 deletion yet cause growth defects and altered DNA-binding properties in vitro. However, a small deletion of the adjacent (downstream) region that abolishes overexpression toxicity has, by itself, no apparent effect on growth or DNA binding. SKO1/ACR1, which encodes a CREB-like repressor protein in yeast, was isolated as a high copy suppressor of the toxicity caused by RAP1 overexpression. Models related to the regulation of Rap1p activity are discussed.
Unigenic evolution: a novel genetic method localizes a putative leucine zipper that mediates dimerization of the Saccharomyces cerevisiae regulator Gcr1p.
Authors: Deminoff S J , Tornow J , Santangelo G M 
Published: January 2021

Abstract
The GCR1 gene of Saccharomyces cerevisiae encodes a transcriptional activator that complexes with Rap1p and, through UASRPG elements (Rap1p DNA binding sites), stimulates efficient expression of glycolytic and translational component genes. To map the functionally important domains in Gcr1p, we combined multiple rounds of random mutagenesis in vitro with in vivo selection of functional genes to locate conserved, or hypomutable, regions. We name this method unigenic evolution, a statistical analysis of mutations in evolutionary variants of a single gene in an otherwise isogenic background. Examination of the distribution of 315 mutations in 24 variant alleles allowed the localization of four hypomutable regions in GCR1 (A, B, C, and D). Dispensable N-terminal (intronic) and C-terminal portions of the evolved region of GCR1 were included in the analysis as controls and were, as expected, not hypomutable. The analysis of several insertion, deletion, and point mutations, combined with a comparison of the hypomutability and hydrophobicity plots of Gcr1p, suggested that some of the hypomutable regions may individually or in combination correspond to functionally important surface domains. In particular, we determined that region D contains a putative leucine zipper and is necessary and sufficient for Gcr1p homodimerization.
Suppressors of a Saccharomyces cerevisiae pkc1 mutation identify alleles of the phosphatase gene PTC1 and of a novel gene encoding a putative basic leucine zipper protein.
Authors: Huang K N , Symington L S 
Published: January 2021

Abstract
The PKC1 gene product, protein kinase C, regulates a mitogen-activated protein kinase (MAPK) cascade, which is implicated in cell wall metabolism. Previously, we identified the pkc1-4 allele in a screen for mutants with increased rates of recombination, indicating that PKC1 may also regulate DNA metabolism. The pkc1-4 allele also conferred a temperature-sensitive (ts) growth defect. Extragenic suppressors were isolated that suppress both the ts and hyperrecombination phenotypes conferred by the pkc1-4 mutation. Eight of these suppressors for into two complementation groups, designated KCS1 and KCS2. KCS1 was cloned and found to encode a novel protein with homology to the basic leucine zipper family of transcription factors. KCS2 is allelic with PTC1, a previously identified type 2C serine/threonine protein phosphatase. Although mutation of either KCS1 or PTC1 causes little apparent phenotype, the kcs1 delta ptc1 delta double mutant fails to grow at 30 degrees. Furthermore, the ptc1 deletion mutation is synthetically lethal in combination with a mutation in MPK1, which encodes a MAPK homologue proposed to act in the PKC1 pathway. Because PTC1 was initially isolated as a component of the Hog1p MAPK pathway, it appears that these two MAPK cascades share a common regulatory feature.
Genetic and molecular analysis of the autosomal component of the primary sex determination signal of Drosophila melanogaster.
Authors: Barbash D A , Cline T W 
Published: January 2021

Abstract
Drosophila sex is determined by the action of the X:A chromosome balance on transcription of Sex-lethal (Sxl), a feminizing switch gene. We obtained loss-of-function mutations in denominator elements of the X:A signal by selecting for dominant suppressors of a female-specific lethal mutation in the numerator element, sisterlessA (sisA). Ten suppressors were recovered in this extensive genome-wide selection. All were mutations in deadpan (dpn), a pleiotropic locus previously discovered to be a denominator element. Detailed genetic and molecular characterization is presented of this diverse set of new dpn alleles including their effects on Sxl. Although selected only for impairment of sex-specific functions, all were also impaired in nonsex-specific functions. Male-lethal effects were anticipated for mutations in a major denominator element, but we found that viability of males lacking dpn function was reduced no more than 50% relative to their dpn- sisters. Moreover, loss of dpn activity in males caused only a modest derepression of the Sxl "establishment" promoter (Sxlpe), the X:A target. By itself, dpn cannot account for the masculinizing effect of increased autosomal ploidy, the effect that gave rise to the concept of the X:A ratio; nevertheless, if there are other denominator elements, our results suggest that their individual contributions to the sex-determination signal are even less than that of dpn. The time course of expression of dpn and of Sxl in dpn mutant backgrounds suggests that dpn is required for sex determination only during the later stages of X:A signaling in males to prevent inappropriate expression of Sxlpe in the face of increasing sis gene product levels.
Major quantitative trait loci affecting honey bee foraging behavior.
Authors: Hunt G J , Page R E , Fondrk M K , Dullum C J 
Published: January 2021

Abstract
We identified two genomic regions that affect the amount of pollen stored in honey bee colonies and influence whether foragers will collect pollen or nectar. We selected for the amount of pollen stored in combs of honey bee colonies, a colony-level trait, and then used random amplified polymorphic DNA (RAPD) markers and interval mapping procedures with data from backcross colonies to identify two quantitative trait loci (pln1 and pln2, LOD 3.1 and 2.3, respectively). Quantitative trait loci effects were confirmed in a separate cross by demonstrating the cosegregation of marker alleles with the foraging behavior of individual workers. Both pln1 and pln2 had an effect on the amount of pollen carried by foragers returning to the colony, as inferred by the association between linked RAPD marker alleles, D8-.3f and 301-.55, and the individual pollen load weights of returning foragers. The alleles of the two marker loci were nonrandomly distributed with respect to foraging task. The two loci appeared to have different effects on foraging behavior. Individuals with alternative alleles for the marker linked to pln2 (but not pln1) differed with respect to the nectar sugar concentration of their nectar loads.
Complementation analyses for 45 mutations encompassing the pink-eyed dilution (p) locus of the mouse.
Authors: Russell L B , Montgomery C S , Cacheiro N L , Johnson D K 
Published: January 2021

Abstract
The homozygous and heterozygous phenotypes are described and characterized for 45 new pink-eyed dilution (p) locus mutations, most of them radiation-induced, that affect survival at various stages of mouse development. Cytogenetically detectable aberrations were found in three of the new p mutations (large deletion, inversion, translocation), with band 7C involved in each case. The complementation map developed from the study of 810 types of compound heterozygotes identifies five functional units: jls and jlm (two distinct juvenile-fitness functions, the latter associated with neuromuscular defects), pl-1 and pl-2 (associated with early-postimplantation and preimplantation death, respectively), and nl [neonatal lethality associated with cleft palate (the frequency of rare "escapers" from this defect varied with the genotype)]. Orientation of these units relative to genetic markers is as follows: centromere, Gas-2, pl-1, jls, jlm p, nl (equatable to cp 1 = Gabrb3); pl-2 probably resides in the c-deletion complex. pl-1 does not mask preimplantation lethals between Gas2 and p; and no genes affecting survival are located between p and cp1. The alleles specifying mottling or darker pigment (generically, pm and px, respectively) probably do not represent deletions of p-coding sequences but could be small rearrangements involving proximal regulatory elements.