bluuebunny/crossref_metadata_2025 huggingface dataset:
Phylogenetic Fate Mapping: Theoretical and Experimental Studies Applied to the Development of Mouse Fibroblasts
Authors: Salipante Stephen J , Thompson James M , Horwitz Marshall S
Published: February 2008

Mutations are an inevitable consequence of cell division. Similarly to how DNA sequence differences allow inferring evolutionary relationships between organisms, we and others have recently demonstrated how somatic mutations may be exploited for phylogenetically reconstructing lineages of individual cells during development in multicellular organisms. However, a problem with such “phylogenetic fate maps” is that they cannot be verified experimentally; distinguishing actual lineages within clonal populations requires direct observation of cell growth, as was used to construct the fate map of Caenorhabditis elegans, but is not possible in higher organisms. Here we employ computer simulation of mitotic cell division to determine how factors such as the quantity of cells, mutation rate, and the number of examined marker sequences contribute to fidelity of phylogenetic fate maps and to explore statistical methods for assessing accuracy. To experimentally evaluate these factors, as well as for the purpose of investigating the developmental origins of connective tissue, we have produced a lineage map of fibroblasts harvested from various organs of an adult mouse. Statistical analysis demonstrates that the inferred relationships between cells in the phylogenetic fate map reflect biological information regarding the origin of fibroblasts and is suggestive of cell migration during mesenchymal development.
Applying Gene Expression, Proteomics and Single-Nucleotide Polymorphism Analysis for Complex Trait Gene Identification
Authors: Stylianou Ioannis M , Affourtit Jason P , Shockley Keith R , Wilpan Robert Y , Abdi Fadi A , Bhardwaj Sanjeev , Rollins Jarod , Churchill Gary A , Paigen Beverly
Published: February 2008

Previous quantitative trait locus (QTL) analysis of an intercross involving the inbred mouse strains NZB/BlNJ and SM/J revealed QTL for a variety of complex traits. Many QTL have large intervals containing hundreds of genes, and methods are needed to rapidly sort through these genes for probable candidates. We chose nine QTL: the three most significant for high-density lipoprotein (HDL) cholesterol, gallstone formation, and obesity. We searched for candidate genes using three different approaches: mRNA microarray gene expression technology to assess >45,000 transcripts, publicly available SNPs to locate genes that are not identical by descent and that contain nonsynonymous coding differences, and a mass-spectrometry-based proteomics technology to interrogate nearly 1000 proteins for differential expression in the liver of the two parental inbred strains. This systematic approach reduced the number of candidate genes within each QTL from hundreds to a manageable list. Each of the three approaches selected candidates that the other two approaches missed. For example, candidate genes such as Apoa2 and Acads had differential protein levels although the mRNA levels were similar. We conclude that all three approaches are important and that focusing on a single approach such as mRNA expression may fail to identify a QTL gene.
Mapping Interspecific Genetic Architecture in a Host–Parasite Interaction System
Authors: Yang Jian , Wu Weiren , Zhu Jun
Published: February 2008

Under a hypothesis that the host–parasite interaction system is governed by genome-for-genome interaction, we propose a genetic model that integrates genetic information from both the host and parasite genomes. The model can be used for mapping quantitative trait loci (QTL) conferring the interaction between host and parasite and detecting interactions among these QTL. A one-dimensional genome-scan strategy is used to map QTL in both the host and parasite genomes simultaneously conditioned on selected pairs of markers controlling the background genetic variation; a two-dimensional genome-scan procedure is conducted to search for epistasis within the host and parasite genomes and interspecific QTL-by-QTL interactions between the host and parasite genomes. A permutation test is adopted to calculate the empirical threshold to control the experimentwise false-positive rate of detected QTL and QTL interactions. Monte Carlo simulations were conducted to examine the reliability and the efficiency of the proposed models and methods. Simulation results illustrated that our methods could provide reasonable estimates of the parameters and adequate powers for detecting QTL and QTL-by-QTL interactions.
Caenorhabditis elegansABCRNAi Transporters Interact Genetically Withrde-2andmut-7
Authors: Sundaram Prema , Han Wang , Cohen Nancy , Echalier Benjamin , Albin John , Timmons Lisa
Published: February 2008

RNA interference (RNAi) mechanisms are conserved and consist of an interrelated network of activities that not only respond to exogenous dsRNA, but also perform endogenous functions required in the fine tuning of gene expression and in maintaining genome integrity. Not surprisingly, RNAi functions have widespread influences on cellular function and organismal development. Previously, we observed a reduced capacity to mount an RNAi response in nine Caenorhabditis elegans mutants that are defective in ABC transporter genes (ABCRNAi mutants). Here, we report an exhaustive study of mutants, collectively defective in 49 different ABC transporter genes, that allowed for the categorization of one additional transporter into the ABCRNAi gene class. Genetic complementation tests reveal functions for ABCRNAi transporters in the mut-7/rde-2 branch of the RNAi pathway. These second-site noncomplementation interactions suggest that ABCRNAi proteins and MUT-7/RDE-2 function together in parallel pathways and/or as multiprotein complexes. Like mut-7 and rde-2, some ABCRNAi mutants display transposon silencing defects. Finally, our analyses reveal a genetic interaction network of ABCRNAi gene function with respect to this part of the RNAi pathway. From our results, we speculate that the coordinated activities of ABCRNAi transporters, through their effects on endogenous RNAi-related mechanisms, ultimately affect chromosome function and integrity.
A Screen for Modifiers of Hedgehog Signaling inDrosophila melanogasterIdentifiesswmandmts
Authors: Casso David J , Liu Songmei , Iwaki D David , Ogden Stacey K , Kornberg Thomas B
Published: February 2008

Signaling by Hedgehog (Hh) proteins shapes most tissues and organs in both vertebrates and invertebrates, and its misregulation has been implicated in many human diseases. Although components of the signaling pathway have been identified, key aspects of the signaling mechanism and downstream targets remain to be elucidated. We performed an enhancer/suppressor screen in Drosophila to identify novel components of the pathway and identified 26 autosomal regions that modify a phenotypic readout of Hh signaling. Three of the regions include genes that contribute constituents to the pathway—patched, engrailed, and hh. One of the other regions includes the gene microtubule star (mts) that encodes a subunit of protein phosphatase 2A. We show that mts is necessary for full activation of Hh signaling. A second region includes the gene second mitotic wave missing (swm). swm is recessive lethal and is predicted to encode an evolutionarily conserved protein with RNA binding and Zn+ finger domains. Characterization of newly isolated alleles indicates that swm is a negative regulator of Hh signaling and is essential for cell polarity.
Genetic Interaction Between theEscherichia coliAcpT Phosphopantetheinyl Transferase and the YejM Inner Membrane Protein
Authors: De Lay Nicholas R , Cronan John E
Published: February 2008

Strain LH530, a mutant of Escherichia coli K-12, was reported by others to show increased outer membrane permeability, temperature-sensitive growth, and reduced synthesis of lipid A. The unmapped mutant gene was found to be suppressed by high-copy-number plasmids carrying the wild-type acpT gene, which encodes a protein that catalyzes a post-translational protein modification, the attachment of 4′-phosphopantetheine. We mapped the strain LH530 mutation to a gene of unknown function, yejM, known to encode an inner membrane protein. The mutation is a yejM nonsense mutation that produces a truncated protein lacking the predicted periplasmic domain. Reconstruction of the mutation gave a strain having the same phenotypes as LH530. In contrast to the nonsense mutants, deletion of the entire yejM gene was lethal. Suppression by AcpT overexpression of the yejM nonsense mutants encoding the truncated proteins was specific to AcpT. Moreover, AcpT overexpression also suppressed the lethality due to deletion of the entire yejM gene and this suppression also did not require that AcpT be enzymatically active. The mechanism whereby overexpression of a specific cytosolic protein bypasses the essentiality of an inner membrane protein is unknown.
The Impact of Dissociation on Transposon-Mediated Disease Control Strategies
Authors: Marshall John M
Published: February 2008

Vector-borne diseases such as malaria and dengue fever continue to be a major health concern through much of the world. The emergence of chloroquine-resistant strains of malaria and insecticide-resistant mosquitoes emphasize the need for novel methods of disease control. Recently, there has been much interest in the use of transposable elements to drive resistance genes into vector populations as a means of disease control. One concern that must be addressed before a release is performed is the potential loss of linkage between a transposable element and a resistance gene. Transposable elements such as P and hobo have been shown to produce internal deletion derivatives at a significant rate, and there is concern that a similar process could lead to loss of the resistance gene from the drive system following a transgenic release. Additionally, transposable elements such as Himar1 have been shown to transpose significantly more frequently when free of exogenous DNA. Here, we show that any transposon-mediated gene drive strategy must have an exceptionally low rate of dissociation if it is to be effective. Additionally, the resistance gene must confer a large selective advantage to the vector to surmount the effects of a moderate dissociation rate and transpositional handicap.
An Asymmetric Model of Heterozygote Advantage at Major Histocompatibility Complex Genes: Degenerate Pathogen Recognition and Intersection Advantage
Authors: Stoffels Rick J , Spencer Hamish G
Published: February 2008

We characterize the function of MHC molecules by the sets of pathogens that they recognize, which we call their “recognition sets.” Two features of the MHC–pathogen interaction may be important to the theory of polymorphism construction at MHC loci: First, there may be a large degree of overlap, or degeneracy, among the recognition sets of MHC molecules. Second, when infected with a pathogen, an MHC genotype may have a higher fitness if that pathogen belongs to the overlapping portion, or intersection, of the two recognition sets of the host, when compared with a genotype that contains that pathogen in only one of its recognition sets. We call this benefit “intersection advantage,” γ, and incorporate it, as well as the degree of recognition degeneracy, m, into a model of heterozygote advantage that utilizes a set-theoretic definition of fitness. Counterintuitively, we show that levels of polymorphism are positively related to m and that a high level of recognition degeneracy is necessary for polymorphism at MHC loci under heterozygote advantage. Increasing γ reduces levels of polymorphism considerably. Hence, if intersection advantage is significant for MHC genotypes, then heterozygote advantage may not explain the very high levels of polymorphism observed at MHC genes.
Nucleotide Polymorphism and Phenotypic Associations Within and Around the phytochrome B2 Locus in European Aspen (Populus tremula, Salicaceae)
Authors: Ingvarsson Pär K , Garcia M Victoria , Luquez Virginia , Hall David , Jansson Stefan
Published: February 2008

We investigated the utility of association mapping to dissect the genetic basis of naturally occurring variation in bud phenology in European aspen (Populus tremula). With this aim, we surveyed nucleotide polymorphism in 13 fragments spanning an 80-kb region surrounding the phytochrome B2 (phyB2) locus. Although polymorphism varies substantially across the phyB2 region, we detected no signs for deviations from neutral expectations. We also identified a total of 41 single nucleotide polymorphisms (SNPs) that were subsequently scored in a mapping population consisting of 120 trees. We identified two nonsynonymous SNPs in the phytochrome B2 gene that were independently associated with variation in the timing of bud set and that explained between 1.5 and 5% of the observed phenotypic variation in bud set. Earlier studies have shown that the frequencies of both these SNPs vary clinally with latitude. Linkage disequilibrium across the region was low, suggesting that the SNPs we identified are strong candidates for being causally linked to variation in bud set in our mapping populations. One of the SNPs (T608N) is located in the “hinge region,” close to the chromophore binding site of the phyB2 protein. The other SNP (L1078P) is located in a region supposed to mediate downstream signaling from the phyB2 locus. The lack of population structure, combined with low levels of linkage disequilibrium, suggests that association mapping is a fruitful method for dissecting naturally occurring variation in Populus tremula.
Drosophila sticky/citron kinase Is a Regulator of Cell-Cycle Progression, Genetically Interacts With Argonaute 1 and Modulates Epigenetic Gene Silencing
Authors: Sweeney Sarah J , Campbell Paula , Bosco Giovanni
Published: February 2008

The sticky/citron kinase protein is a conserved regulator of cell-cycle progression from invertebrates to humans. While this kinase is essential for completion of cytokinesis, sticky/citron kinase phenotypes disrupting neurogenesis and cell differentiation suggest additional non-cell-cycle functions. However, it is not known whether these phenotypes are an indirect consequence of sticky mutant cell-cycle defects or whether they define a novel function for this kinase. We have isolated a temperature-sensitive allele of the Drosophila sticky gene and we show that sticky/citron kinase is required for histone H3-K9 methylation, HP1 localization, and heterochromatin-mediated gene silencing. sticky genetically interacts with Argonaute 1 and sticky mutants exhibit context-dependent Su(var) and E(var) activity. These observations indicate that sticky/citron kinase functions to regulate both actin–myosin-mediated cytokinesis and epigenetic gene silencing, possibly linking cell-cycle progression to heterochromatin assembly and inheritance of gene expression states.
A New Bayesian Method to Identify the Environmental Factors That Influence Recent Migration
Authors: Faubet Pierre , Gaggiotti Oscar E
Published: February 2008

We present a new multilocus genotype method that makes inferences about recent immigration rates and identifies the environmental factors that are more likely to explain observed gene flow patterns. It also estimates population-specific inbreeding coefficients, allele frequencies, and local population FST's and performs individual assignments. We generate synthetic data sets to determine the region of the parameter space where our method is and is not able to provide accurate estimates. Our simulation study indicates that reliable results can be obtained when the global level of genetic differentiation (FST) is >1%, the number of loci is only 10, and sample sizes are of the order of 50 individuals per population. We illustrate our method by applying it to Pakistani human data, considering altitude and geographic distance as explanatory factors. Our results suggest that altitude explains better the genetic data than geographic distance. Additionally, they show that southern low-altitude populations have higher migration rates than northern high-altitude ones.
Neofunctionalization of Duplicated Genes Under the Pressure of Gene Conversion
Authors: Teshima Kosuke M , Innan Hideki
Published: February 2008

Neofunctionalization occurs when a neofunctionalized allele is fixed in one of duplicated genes. This is a simple fixation process if duplicated genes accumulate mutations independently. However, the process is very complicated when duplicated genes undergo concerted evolution by gene conversion. Our simulations demonstrate that the process could be described with three distinct stages. First, a newly arisen neofunctionalized allele increases in frequency by selection, but gene conversion prevents its complete fixation. These two factors (selection and gene conversion) that work in opposite directions create an equilibrium, and the time during which the frequency of the neofunctionalized allele drifts around the equilibrium value is called the temporal equilibrium stage. During this temporal equilibrium stage, it is possible that gene conversion is inactivated by mutations, which allow the complete fixation of the neofunctionalized allele. And then, permanent neofunctionalization is achieved. This article develops basic population genetics theories on the process to permanent neofunctionalization under the pressure of gene conversion. We obtain the probability and time that the frequency of a newly arisen neofunctionalized allele reaches the equilibrium value. It is also found that during the temporal equilibrium stage, selection exhibits strong signature in the divergence in the DNA sequences between the duplicated genes. The spatial distribution of the divergence likely has a peak around the site targeted by selection. We provide an analytical expression of the pattern of divergence and apply it to the human red- and green-opsin genes. The theoretical prediction well fits the data when we assume that selection is operating for the two amino acid differences in exon 5, which are believed to account for the major part of the functional difference between the red and green opsins.
Population Biology of Cytoplasmic Incompatibility: Maintenance and Spread of Cardinium Symbionts in a Parasitic Wasp
Authors: Perlman Steve J , Kelly Suzanne E , Hunter Martha S
Published: February 2008

Bacteria that cause cytoplasmic incompatibility (CI) are perhaps the most widespread parasites of arthropods. CI symbionts cause reproductive failure when infected males mate with females that are either uninfected or infected with a different, incompatible strain. Until recently, CI was known to be caused only by the α-proteobacterium Wolbachia. Here we present the first study of the population biology of Cardinium, a recently discovered symbiont in the Bacteroidetes that causes CI in the parasitic wasp Encarsia pergandiella (Hymenoptera: Aphelinidae). Cardinium occurs at high frequency (∼92%) in the field. Using wasps that were recently collected in the field, we measured parameters that are crucial for understanding how CI spreads and is maintained in its host. CI Cardinium exhibits near-perfect rates of maternal transmission, causes a strong reduction in viable offspring in incompatible crosses, and induces a high fecundity cost, with infected females producing 18% fewer offspring in the first 4 days of reproduction. We found no evidence for paternal transmission or horizontal transmission of CI Cardinium through parasitism of an infected conspecific. No evidence for cryptic parthenogenesis in infected females was found, nor was sex allocation influenced by infection. We incorporated our laboratory estimates into a model of CI dynamics. The model predicts a high stable equilibrium, similar to what we observed in the field. Interestingly, our model also predicts a high threshold frequency of CI invasion (20% for males and 24% for females), below which the infection is expected to be lost. We consider how this threshold may be overcome, focusing in particular on the sensitivity of CI models to fecundity costs. Overall our results suggest that the factors governing the dynamics of CI Wolbachia and Cardinium are strikingly similar.
Low Levels of Polymorphism in Genes That Control the Activation of Defense Response inArabidopsis thaliana
Authors: Bakker Erica G , Traw M Brian , Toomajian Christopher , Kreitman Martin , Bergelson Joy
Published: February 2008

Plants use signaling pathways involving salicylic acid, jasmonic acid, and ethylene to defend against pathogen and herbivore attack. Many defense response genes involved in these signaling pathways have been characterized, but little is known about the selective pressures they experience. A representative set of 27 defense response genes were resequenced in a worldwide set of 96 Arabidopsis thaliana accessions, and patterns of single nucleotide polymorphisms (SNPs) were evaluated in relation to an empirical distribution of SNPs generated from either 876 fragments or 236 fragments with >400 bp coding sequence (this latter set was selected for comparisons with coding sequences) distributed across the genomes of the same set of accessions. Defense response genes have significantly fewer protein variants, display lower levels of nonsynonymous nucleotide diversity, and have fewer nonsynonymous segregating sites. The majority of defense response genes appear to be experiencing purifying selection, given the dearth of protein variation in this set of genes. Eight genes exhibit some evidence of partial selective sweeps or transient balancing selection. These results therefore provide a strong contrast to the high levels of balancing selection exhibited by genes at the upstream positions in these signaling pathways.
Lethal Accumulation of Guanylic Nucleotides inSaccharomyces cerevisiae HPT1-Deregulated Mutants
Authors: Breton Annick , Pinson Benoît , Coulpier Fanny , Giraud Marie-France , Dautant Alain , Daignan-Fornier Bertrand
Published: February 2008

Guanylic nucleotide biosynthesis is a conserved and highly regulated process. Drugs reducing GMP synthesis affect the immunological response and mutations enabling guanylic-derivative recycling lead to severe mental retardation. While the effects of decreased GMP synthesis have been well documented, the consequences of GMP overproduction in eukaryotes are poorly understood. In this work, we selected and characterized several mutations making yeast hypoxanthine–guanine phosphoribosyltransferase insensitive to feedback inhibition by GMP. In these mutants, accumulation of guanylic nucleotides can be triggered by addition of extracellular guanine. We show that such an accumulation is highly toxic for yeast cells and results in arrest of proliferation and massive cell death. This growth defect could be partially suppressed by overexpression of Rfx1p, a transcriptional repressor of the DNA damage response pathway. Importantly, neither guanylic nucleotide toxicity nor its suppression by Rfx1p was associated with an alteration of forward mutation frequency.
Recruitment and Dissociation of Nonhomologous End Joining Proteins at a DNA Double-Strand Break in Saccharomyces cerevisiae
Authors: Wu Dongliang , Topper Leana M , Wilson Thomas E
Published: February 2008

Nonhomologous end joining (NHEJ) is an important DNA double-strand-break (DSB) repair pathway that requires three protein complexes in Saccharomyces cerevisiae: the Ku heterodimer (Yku70-Yku80), MRX (Mre11-Rad50-Xrs2), and DNA ligase IV (Dnl4-Lif1), as well as the ligase-associated protein Nej1. Here we use chromatin immunoprecipitation from yeast to dissect the recruitment and release of these protein complexes at HO-endonuclease-induced DSBs undergoing productive NHEJ. Results revealed that Ku and MRX assembled at a DSB independently and rapidly after DSB formation. Ligase IV appeared at the DSB later than Ku and MRX and in a strongly Ku-dependent manner. Ligase binding was extensive but slightly delayed in rad50 yeast. Ligase IV binding occurred independently of Nej1, but instead promoted loading of Nej1. Interestingly, dissociation of Ku and ligase from unrepaired DSBs depended on the presence of an intact MRX complex and ATP binding by Rad50, suggesting a possible role of MRX in terminating a NHEJ repair phase. This activity correlated with extended DSB resection, but limited degradation of DSB ends occurred even in MRX mutants with persistently bound Ku. These findings reveal the in vivo assembly of the NHEJ repair complex and shed light on the mechanisms controlling DSB repair pathway utilization.
A Combination of cis and trans Control Can Solve the Hotspot Conversion Paradox
Authors: Peters A D
Published: February 2008

There is growing evidence that in a variety of organisms the majority of meiotic recombination events occur at a relatively small fraction of loci, known as recombination hotspots. If hotspot activity results from the DNA sequence at or near the hotspot itself (in cis), these hotspots are expected to be rapidly lost due to biased gene conversion, unless there is strong selection in favor of the hotspot itself. This phenomenon makes it very difficult to maintain existing hotspots and even more difficult for new hotspots to evolve; it has therefore come to be known as the “hotspot conversion paradox.” I develop an analytical framework for exploring the evolution of recombination hotspots under the forces of selection, mutation, and conversion. I derive the general conditions under which cis- and trans-controlled hotspots can be maintained, as well as those under which new hotspots controlled by both a cis and a trans locus can invade a population. I show that the conditions for maintenance of and invasion by trans- or cis-plus-trans-controlled hotspots are broader than for those controlled entirely in cis. Finally, I show that a combination of cis and trans control may allow for long-lived polymorphisms in hotspot activity, the patterns of which may explain some recently observed features of recombination hotspots.
Heterozygous Screen in Saccharomyces cerevisiae Identifies Dosage-Sensitive Genes That Affect Chromosome Stability
Authors: Strome Erin D , Wu Xiaowei , Kimmel Marek , Plon Sharon E
Published: February 2008

Current techniques for identifying mutations that convey a small increased cancer risk or those that modify cancer risk in carriers of highly penetrant mutations are limited by the statistical power of epidemiologic studies, which require screening of large populations and candidate genes. To identify dosage-sensitive genes that mediate genomic stability, we performed a genomewide screen in Saccharomyces cerevisiae for heterozygous mutations that increase chromosome instability in a checkpoint-deficient diploid strain. We used two genome stability assays sensitive enough to detect the impact of heterozygous mutations and identified 172 heterozygous gene disruptions that affected chromosome fragment (CF) loss, 45% of which also conferred modest but statistically significant instability of endogenous chromosomes. Analysis of heterozygous deletion of 65 of these genes demonstrated that the majority increased genomic instability in both checkpoint-deficient and wild-type backgrounds. Strains heterozygous for COMA kinetochore complex genes were particularly unstable. Over 50% of the genes identified in this screen have putative human homologs, including CHEK2, ERCC4, and TOPBP1, which are already associated with inherited cancer susceptibility. These findings encourage the incorporation of this orthologous gene list into cancer epidemiology studies and suggest further analysis of heterozygous phenotypes in yeast as models of human disease resulting from haplo-insufficiency.
The Caenorhabditis elegans ekl (Enhancer of ksr-1 Lethality) Genes Include Putative Components of a Germline Small RNA Pathway
Authors: Rocheleau Christian E , Cullison Kevin , Huang Kai , Bernstein Yelena , Spilker Annina C , Sundaram Meera V
Published: February 2008

A canonical Ras–ERK signaling pathway specifies the fate of the excretory duct cell during Caenorhabditis elegans embryogenesis. The paralogs ksr-1 and ksr-2 encode scaffolding proteins that facilitate signaling through this pathway and that act redundantly to promote the excretory duct fate. In a genomewide RNAi screen for genes that, like ksr-2, are required in combination with ksr-1 for the excretory duct cell fate, we identified 16 “ekl” (enhancer of ksr-1 lethality) genes that are largely maternally required and that have molecular identities suggesting roles in transcriptional or post-transcriptional gene regulation. These include the Argonaute gene csr-1 and a specific subset of other genes implicated in endogenous small RNA processes, orthologs of multiple components of the NuA4/Tip60 histone acetyltransferase and CCR4/NOT deadenylase complexes, and conserved enzymes involved in ubiquitination and deubiquitination. The identification of four small RNA regulators (csr-1, drh-3, ego-1, and ekl-1) that share the Ekl phenotype suggests that these genes define a functional pathway required for the production and/or function of particular germline small RNA(s). These small RNAs and the other ekl genes likely control the expression of one or more regulators of Ras–ERK signaling that function at or near the level of kinase suppressor of Ras (KSR).
Genetic Modification of the Schisis Phenotype in a Mouse Model of X-Linked Retinoschisis
Authors: Johnson Britt A , Aoyama Natsuyo , Friedell Nicole H , Ikeda Sakae , Ikeda Akihiro
Published: February 2008

X-linked retinoschisis (XLRS) is an inherited form of macular degeneration that is caused by mutations in the retinoschisin (RS1) gene. In addition to macular degeneration, other major characteristics of XLRS include splitting of the retina (schisis) and impaired synaptic transmission as indicated by a reduction in the electroretinogram b-wave. It has been known that patients carrying RS1 mutations show a broad range of phenotypic variability. Interestingly, phenotypic variation is observed even among family members with the same RS1 mutation, suggesting the existence of genetic or environmental factors that contribute to the severity of XLRS. However, in the human population, the cause of phenotypic variability and the contribution of genetic modifiers for this relatively rare disease are difficult to study and poorly understood. In this study, using a mouse model for XLRS, we show that genetic factors can contribute to the severity of the retinoschisis phenotype. We report evidence of a major genetic modifier of Rs1, which affects the disease severity in these animals. A quantitative trait locus (QTL), named modifier of Rs1  1 (Mor1), is mapped on chromosome (Chr) 7. When homozygous, the Mor1 allele from the inbred mouse strain AKR/J diminishes the severity of the schisis phenotype in Rs1tmgc1/Y male and Rs1tmgc1/Rs1tmgc1 female mice. We also show that the penetrance of the disease phenotype is affected by additional genetic factor(s). Our study suggests that multiple genetic modifiers could potentially be responsible for the phenotypic variation in human XLRS.
The Cost of Expression of Escherichia coli lac Operon Proteins Is in the Process, Not in the Products
Authors: Stoebel Daniel M , Dean Antony M , Dykhuizen Daniel E
Published: February 2008

Transcriptional regulatory networks allow bacteria to express proteins only when they are needed. Adaptive hypotheses explaining the evolution of regulatory networks assume that unneeded expression is costly and therefore decreases fitness, but the proximate cause of this cost is not clear. We show that the cost in fitness to Escherichia coli strains constitutively expressing the lactose operon when lactose is absent is associated with the process of making the lac gene products, i.e., associated with the acts of transcription and/or translation. These results reject the hypotheses that regulation exists to prevent the waste of amino acids in useless protein or the detrimental activity of unnecessary proteins. While the cost of the process of protein expression occurs in all of the environments that we tested, the expression of the lactose permease could be costly or beneficial, depending on the environment. Our results identify the basis of a single selective pressure likely acting across the entire E. coli transcriptome.
Role of Proliferating Cell Nuclear Antigen Interactions in the Mismatch Repair-Dependent Processing of Mitotic and Meiotic Recombination Intermediates in Yeast
Authors: Stone Jana E , Ozbirn Regan Gealy , Petes Thomas D , Jinks-Robertson Sue
Published: February 2008

The mismatch repair (MMR) system is critical not only for the repair of DNA replication errors, but also for the regulation of mitotic and meiotic recombination processes. In a manner analogous to its ability to remove replication errors, the MMR system can remove mismatches in heteroduplex recombination intermediates to generate gene conversion events. Alternatively, such mismatches can trigger an MMR-dependent antirecombination activity that blocks the completion of recombination, thereby limiting interactions between diverged sequences. In Saccharomyces cerevisiae, the MMR proteins Msh3, Msh6, and Mlh1 interact with proliferating cell nuclear antigen (PCNA), and mutations that disrupt these interactions result in a mutator phenotype. In addition, some mutations in the PCNA-encoding POL30 gene increase mutation rates in an MMR-dependent manner. In the current study, pol30, mlh1, and msh6 mutants were used to examine whether MMR–PCNA interactions are similarly important during mitotic and meiotic recombination. We find that MMR–PCNA interactions are important for repairing mismatches formed during meiotic recombination, but play only a relatively minor role in regulating the fidelity of mitotic recombination.
Evidence of Spatially Varying Selection Acting on Four Chromatin-Remodeling Loci in Drosophila melanogaster
Authors: Levine Mia T , Begun David J
Published: February 2008

The packaging of DNA into proper chromatin structure contributes to transcriptional regulation. This packaging is environment sensitive, yet its role in adaptation to novel environmental conditions is completely unknown. We set out to identify candidate chromatin-remodeling loci that are differentiated between tropical and temperate populations in Drosophila melanogaster, an ancestrally equatorial African species that has recently colonized temperate environments around the world. Here we describe sequence variation at seven such chromatin-remodeling loci, four of which (chd1, ssrp, chm, and glu) exhibit strong differentiation between tropical and temperate populations. An in-depth analysis of chm revealed sequence differentiation restricted to a small portion of the gene, as well as evidence of clinal variation along the east coasts of both the United States and Australia. The functions of chd1, chm, ssrp, and glu point to several novel hypotheses for the role of chromatin-based transcriptional regulation in adaptation to a novel environment. Specifically, both stress-induced transcription and developmental homeostasis emerge as potential functional targets of environment-dependent selection.
The Caenorhabditis elegans PcG-like Gene sop-2 Regulates the Temporal and Sexual Specificities of Cell Fates
Authors: Cai Qingchun , Sun Yinyan , Huang Xinxin , Guo Cong , Zhang Yuxia , Zhu Zuoyan , Zhang Hong
Published: February 2008

How spatial, temporal, and sexual specific cues are integrated to specify distinct cell fates during multicellular organism development is largely unknown. Here we demonstrate that the Caenorhabditis elegans PcG-like gene sop-2 determines the temporal and sexual specificities of a row of hypodermal seam cells, in addition to specifying their positional identities. Loss-of-function of sop-2 causes premature expression of adult fates at larval stages. sop-2 acts upstream of lin-29 in the heterochronic pathway and genetically interacts with other heterochronic genes in specifying the temporal fates of seam cells at different larval stages. We show that the number of ALG-1-containing P bodies is increased in seam cells in sop-2 mutants. Furthermore, the microRNA-mediated repression of a heterochronic gene reporter is enhanced in sop-2 mutants. Mutations in sop-2 also cause partial hermaphrodite-to-male sexual transformations. The homeotic transformations, heterochronic defects, and sexual transformations can occur concomitantly in sop-2 mutants. In summary, our studies reveal that sop-2 integrates spatial, temporal, and sexual cues during C. elegans development.
Common Reed (Phragmites australis) Response to Mowing and Herbicide Application
Authors: Derr Jeffrey F.
Published: February 2008

Common reed is an invasive species that has overtaken wetland habitats in the eastern United States and can spread into roadsides, turf, and ornamental sites. The postemergence grass herbicides used in nursery crops and turf, clethodim, fenoxaprop, fluazifop, and sethoxydim, did not control common reed. Dithiopyr, MSMA, and quinclorac also did not control this weed. Glyphosate applied at 2.24 kg ai/ha (2.0 lb ai/ac) was more effective in preventing regrowth of common reed than glufosinate at 1.12 kg/ha (1.0 lb ai/ac). Mowing every 2, 4, or 8 wk controlled common reed 93, 81, and 69%, respectively, by the end of the growing season, but only reduced regrowth by approximately 55% the following May. Applying glyphosate at 2% v/v either 1 mo after a mowing or 2 wk prior to mowing reduced common reed regrowth the following May by approximately 90%. Applying glyphosate without mowing provided similar common reed control the following spring compared to glyphosate combined with a single mowing. Common reed regrew in all treated plots 1 yr after study initiation, indicating that control treatments must be repeated if common reed is to be eradicated from a site.
Herbicide and Native Grass Seeding Effects on Sulfur Cinquefoil (Potentilla Recta)-Infested Grasslands
Authors: Endress Bryan A. , Parks Catherine G. , Naylor Bridgett J. , Radosevich Steven R.
Published: February 2008

Sulfur cinquefoil is an exotic, perennial forb that invades a wide range of ecosystems in western North America. It forms dense populations and often threatens native plant species and communities. In this study, we address the following questions: (1) what herbicides, rates, and application times are most effective at reducing sulfur cinquefoil abundance while having the least impact on native plants; and (2) does postherbicide seeding with native grass species increase native plant abundance? In 2002, we experimentally examined the effects of five herbicides (dicamba + 2,4-D; metsulfuron-methyl; triclopyr; glyphosate; and picloram) at two rates of application (low and high), three application times (early summer, fall, and a combined early summer–fall treatment), and two postherbicide seed addition treatments (seeded or not seeded) on sulfur cinquefoil abundance, plant community composition, and species richness. Experimental plots were monitored through 2005. Picloram was the most effective herbicide at reducing sulfur cinquefoil density, the proportion of remaining adult plants, and seed production. The effects of picloram continued to be evident after 3 yr, with 80% reduction of sulfur cinquefoil in 2005. In addition, seeding of native grass seeds alone (no herbicide application) reduced the proportion of sulfur cinquefoil plants that were reproductively active. Despite reductions in sulfur cinquefoil abundance, all treatments remained dominated by exotic species because treated areas transitioned from exotic forb- to exotic grass-dominated communities. However, a one-time herbicide application controlled sulfur cinquefoil for at least 3 yr, and therefore might provide a foundation to begin ecological restoration. Herbicide applications alone likely are to be insufficient for long-term sulfur cinquefoil control without further modification of sites through native grass or forb seeding. Integrating herbicides with native plant seeding to promote the development of plant communities that are resistant to sulfur cinquefoil invasion is a promising management approach to ecological restoration.
Relationships Between Western Juniper (Juniperus occidentalis) and Understory Vegetation
Authors: Coultrap D. E. , Fulgham K. O. , Lancaster D. L. , Gustafson J. , Lile D. F. , George M. R.
Published: February 2008

Western juniper has been actively invading sagebrush plant communities for about 130 yr. Western juniper canopy cover generally increases as western juniper invades sagebrush steppe communities and succession progresses toward a western juniper woodland. Our goal was to estimate the impact of juniper invasion and canopy increase on understory vegetation structure and productivity on 101 sites in northeastern California. The primary objectives of this study were to: (1) examine the influence of increasing western juniper canopy cover on the composition and productivity of understory vegetation; and (2) assess the effects of western juniper removal on understory vegetation. Sites in early, mid-, and late successional stages and sites on the same soils that had not been invaded were selected. Sites where western juniper had been removed by prescribed fire, mechanical, or chemical methods were compared to adjacent untreated sites. Western juniper canopy cover, understory cover and species composition, productivity, and bare ground were determined at each site during May through July 2005 and 2006. Regression analysis was used to evaluate the relationship between western juniper canopy cover and understory vegetation parameters. Logistic regression was used to detect understory differences between treated (juniper removed) and untreated (juniper not removed) sites. A significant relationship was found between western juniper canopy cover and understory species richness, shrub cover, forb cover, total grass cover, cheatgrass cover, herbaceous productivity, and bare ground. Removal of western juniper increased total grass cover, cheatgrass cover, and productivity, and reduced bare ground. The results of this study support findings by researchers in other states that western juniper influences plant community structure and productivity, and removal of western juniper might reverse these changes in structure, but also might increase opportunities for invasion of cheatgrass.
Forces Necessary to Initiate Dispersal for Three Tumbleweeds
Authors: Baker Dirk V. , Beck K. George , Bienkiewicz Bogusz J. , Bjostad Louis B.
Published: February 2008

Although diffuse knapweed, kochia, and Russian thistle are important tumbleweeds of the western United States, environmental factors contributing to their dispersal are not well understood. Bolting rosettes of these species were transplanted to pots and reared in a common garden to determine the affect of postsenescence water on stem strength. There were no differences in stem strength among three water treatments for Russian thistle. Kochia, under moderate water treatment, required more than twice the force to break compared to plants under the zero and high water treatments. In contrast, diffuse knapweed plants under zero water treatment required four to six times greater force to break compared to plants under the moderate and high water treatments. There was a strong difference in diffuse knapweed stem strength between field collection sites that corresponded to observed differences in proportion of plants tumbling. A wind tunnel was used to develop a conversion factor between force and wind velocity. Wind velocities necessary to break diffuse knapweed stems ranged from 16 to 37 m/s (36 to 77 mph).
Feeding Impacts of a Leafy Spurge (Euphorbia esula) Biological Control Agent on a Native Plant, Euphorbia robusta
Authors: Baker John L. , Webber Nancy A. P.
Published: February 2008

The biological control agent Aphthona nigriscutis Foudras (Chrysomelidae) established in Fremont County, WY since 1992 on leafy spurge was released into a mixed stand a native plant Euphorbia robusta Engelm. During host range testing, E. robusta was a likely host for A. nigriscutis under laboratory conditions. In 1999, A. nigriscutis was observed feeding on both E. esula and 31 of 36 E. robusta plants present on about 2 ha (5 ac) where the visually estimated E. esula canopy cover was 50%. By August 2001, E. esula cover had declined to less than 5% and E. robusta plants had increased to 450 plants with 26 (5.8%) showing feeding damage. In 2006 Euphorbia esula ground cover was 2% and of 598 E. robusta plants originally marked, 391 could be located and four of these had damage consistent with A. nigriscutis feeding. For the 8-yr period, E. esula ground cover was inversely correlated to E. robusta density and positively correlated to A. nigriscutis feeding damage on E. robusta. This study shows that while also acceptable to A. nigriscutis in the field, feeding on E. robusta declined with declining densities of the target weed while E. robusta population densities increased. It seems that some risk in this regard is acceptable in light of the damage from the target weed and the generally high level of selectivity provided by biological control agents.
The Invasive Species Assessment Protocol: A Tool for Creating Regional and National Lists of Invasive Nonnative Plants that Negatively Impact Biodiversity
Authors: Randall John M. , Morse Larry E. , Benton Nancy , Hiebert Ron , Lu Stephanie , Killeffer Terri
Published: February 2008

We developed a protocol for categorizing nonnative plants according to their negative impacts on biodiversity in a large area such as a state, nation, or ecological region. Our objective was to provide a tool that makes the process of identifying, categorizing, and listing nonnative plants that cause negative impacts to biodiversity analytic, transparent, and equitable and that yields lists that are useful to researchers, land managers, regulators, consumers, and commercial interests such as the nursery industry. The protocol was designed to distinguish between species that cause high, medium, low, or insignificant negative impacts to native biodiversity within the state, region, or nation of interest. It consists of 20 multiple-choice questions grouped into four sections, which each address a major aspect of a species' total impact and when combined yield an overall “Invasive Species Impact Rank” or “I-Rank” (high, medium, low, or insignificant). The nonprofit organization NatureServe is now using this protocol to assess the estimated 3,500 nonnative vascular plant species that are established in the United States to create a national list prioritized by negative impact on biodiversity. The protocol and additional information are available on the Internet athttp://www.natureserve.org/getData/plantData.jsp, and over 500 completed species assessments are available through NatureServe Explorer (http://www.natureserve.org/explorer/).