bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence for Positive Selection in Foot-and-Mouth Disease Virus Capsid Genes From Field Isolates
Authors: Haydon Daniel T , Bastos Armanda D , Knowles Nick J , Samuel Alan R 
Published: April 2021

Abstract
The nature of selection on capsid genes of foot-and-mouth disease virus (FMDV) was characterized by examining the ratio of nonsynonymous to synonymous substitutions in 11 data sets of sequences obtained from six different serotypes of FMDV. Using a method of analysis that assigns each codon position to one of a number of estimated values of nonsynonymous to synonymous ratio, significant evidence of positive selection was identified in 5 data sets, operating at 1-7% of codon positions. Evidence of positive selection was identified in complete capsid sequences of serotypes A and C and in VP1 sequences of serotypes SAT 1 and 2. Sequences of serotype SAT-2 recovered from a persistently infected African buffalo also revealed evidence for positive selection. Locations of codons under positive selection coincide closely with those of antigenic sites previously identified with the use of monoclonal antibody escape mutants. The vast majority of codons are under mild to strong purifying selection. However, these results suggest that arising antigenic variants benefit from a selective advantage in their interaction with the immune system, either during the course of an infection or in transmission to individuals with previous exposure to antigen. Analysis of amino acid usage at sites under positive selection indicates that this selective advantage can be conferred by amino acid substitutions that share physicochemically similar properties.
WW Domains of Rsp5p Define Different Functions: Determination of Roles in Fluid Phase and Uracil Permease Endocytosis in Saccharomyces cerevisiae
Authors: Gajewska Beata , Kamińska Joanna , Jesionowska Alicja , Martin Nancy C , Hopper Anita K , Żoła̧dek Teresa 
Published: April 2021

Abstract
Rsp5p, ubiquitin-protein ligase, an enzyme of the ubiquitination pathway, contains three WW domains that mediate protein-protein interactions. To determine if these domains adapt Rsp5p to a subset of substrates involved in numerous cellular processes, we generated mutations in individual or combinations of the WW domains. The rsp5-w1, rsp5-w2, and rsp5-w3 mutant alleles complement RSP5 deletions at 30°. Thus, individual WW domains are not essential. Each rsp5-w mutation caused temperature-sensitive growth. Among variants with mutations in multiple WW domains, only rsp5-w1w2 complemented the deletion. Thus, the WW3 domain is sufficient for Rsp5p essential functions. To determine whether rsp5-w mutations affect endocytosis, fluid phase and uracil permease (Fur4p) endocytosis was examined. The WW3 domain is important for both processes. WW2 appears not to be important for fluid phase endocytosis whereas it is important for Fur4p endocytosis. In contrast, the WW1 domain affects fluid phase endocytosis, but it does not appear to function in Fur4p endocytosis. Thus, various WW domains play different roles in the endocytosis of these two substrates. Rsp5p is located in the cytoplasm in a punctate pattern that does not change during the cell cycle. Altering WW domains does not change the location of Rsp5p.
Analysis of Expressed Sequence Tags From Two Starvation, Time-of-Day-Specific Libraries of Neurospora crassa Reveals Novel Clock-Controlled Genes
Authors: Zhu Hua , Nowrousian Minou , Kupfer Doris , Colot Hildur V , Berrocal-Tito Gloria , Lai Hongshing , Bell-Pedersen Deborah , Roe Bruce A , Loros Jennifer J , Dunlap Jay C 
Published: April 2021

Abstract
In an effort to determine genes that are expressed in mycelial cultures of Neurospora crassa over the course of the circadian day, we have sequenced 13,000 cDNA clones from two time-of-day-specific libraries (morning and evening library) generating ∼20,000 sequences. Contig analysis allowed the identification of 445 unique expressed sequence tags (ESTs) and 986 ESTs present in multiple cDNA clones. For ∼50% of the sequences (710 of 1431), significant matches to sequences in the National Center for Biotechnology Information database (of known or unknown function) were detected. About 50% of the ESTs (721 of 1431) showed no similarity to previously identified genes. We hybridized Northern blots with probes derived from 26 clones chosen from contigs identified by multiple cDNA clones and EST sequences. Using these sequences, the representation of genes among the morning and evening sequences, respectively, in most cases does not reflect their expression patterns over the course of the day. Nevertheless, we were able to identify four new clock-controlled genes. On the basis of these data we predict that a significant proportion of the expressed Neurospora genes may be regulated by the circadian clock. The mRNA levels of all four genes peak in the subjective morning as is the case with previously identified ccgs.
Transcriptional Regulators of the Schizosaccharomyces pombe fbp1 Gene Include Two Redundant Tup1p-like Corepressors and the CCAAT Binding Factor Activation Complex
Authors: Janoo Rozmin T K , Neely Lori A , Braun Burkhard R , Whitehall Simon K , Hoffman Charles S 
Published: April 2021

Abstract
The Schizosaccharomyces pombe fbp1 gene, which encodes fructose-1,6-bis-phosphatase, is transcriptionally repressed by glucose through the activation of the cAMP-dependent protein kinase A (PKA) and transcriptionally activated by glucose starvation through the activation of a mitogen-activated protein kinase (MAPK). To identify transcriptional regulators acting downstream from or in parallel to PKA, we screened an adh-driven cDNA plasmid library for genes that increase fbp1 transcription in a strain with elevated PKA activity. Two such clones express amino-terminally truncated forms of the S. pombe tup12 protein that resembles the Saccharomyces cerevisiae Tup1p global corepressor. These clones appear to act as dominant negative alleles. Deletion of both tup12 and the closely related tup11 gene causes a 100-fold increase in fbp1-lacZ expression, indicating that tup11 and tup12 are redundant negative regulators of fbp1 transcription. In strains lacking tup11 and tup12, the atf1-pcr1 transcriptional activator continues to play a central role in fbp1-lacZ expression; however, spc1 MAPK phosphorylation of atf1 is no longer essential for its activation. We discuss possible models for the role of tup11- and tup12-mediated repression with respect to signaling from the MAPK and PKA pathways. A third clone identified in our screen expresses the php5 protein subunit of the CCAAT-binding factor (CBF). Deletion of php5 reduces fbp1 expression under both repressed and derepressed conditions. The CBF appears to act in parallel to atf1-pcr1, although it is unclear whether or not CBF activity is regulated by PKA.
Construction of a Genetic Linkage Map in Tetraploid Species Using Molecular Markers
Authors: Luo Z W , Hackett C A , Bradshaw J E , McNicol J W , Milbourne D 
Published: April 2021

AbstractThis article presents methodology for the construction of a linkage map in an autotetraploid species, using either codominant or dominant molecular markers scored on two parents and their full-sib progeny. The steps of the analysis are as follows: identification of parental genotypes from the parental and offspring phenotypes; testing for independent segregation of markers; partition of markers into linkage groups using cluster analysis; maximum-likelihood estimation of the phase, recombination frequency, and LOD score for all pairs of markers in the same linkage group using the EM algorithm; ordering the markers and estimating distances between them; and reconstructing their linkage phases. The information from different marker configurations about the recombination frequency is examined and found to vary considerably, depending on the number of different alleles, the number of alleles shared by the parents, and the phase of the markers. The methods are applied to a simulated data set and to a small set of SSR and AFLP markers scored in a full-sib population of tetraploid potato.
Differential Evolution of Eastern Equine Encephalitis Virus Populations in Response to Host Cell Type
Authors: Cooper Lynn A , Scott Thomas W 
Published: April 2021

Abstract
Arthropod-borne viruses (arboviruses) cycle between hosts in two widely separated taxonomic groups, vertebrate amplifying hosts and invertebrate vectors, both of which may separately or in concert shape the course of arbovirus evolution. To elucidate the selective pressures associated with virus replication within each portion of this two-host life cycle, the effects of host type on the growth characteristics of the New World alphavirus, eastern equine encephalitis (EEE) virus, were investigated. Multiple lineages of an ancestral EEE virus stock were repeatedly transferred through either mosquito or avian cells or in alternating passages between these two cell types. When assayed in both cell types, derived single host lineages exhibited significant differences in infectivity, growth pattern, plaque morphology, and total virus yield, demonstrating that this virus is capable of host-specific evolution. Virus lineages grown in alternation between the two cell types expressed intermediate phenotypes consistent with dual adaptation to both cellular environments. Both insect-adapted and alternated lineages greatly increased in their ability to infect insect cells. These results indicate that different selective pressures exist for virus replication within each portion of the two-host life cycle, and that alternation of hosts selects for virus populations well adapted for replication in both host systems.
On the Origin of Self-Incompatibility Haplotypes: Transition Through Self-Compatible Intermediates
Authors: Uyenoyama Marcy K , Zhang Yu , Newbigin Ed 
Published: April 2021

Abstract
Self-incompatibility (SI) in flowering plants entails the inhibition of fertilization by pollen that express specificities in common with the pistil. In species of the Solanaceae, Rosaceae, and Scrophulariaceae, the inhibiting factor is an extracellular ribonuclease (S-RNase) secreted by stylar tissue. A distinct but as yet unknown gene (provisionally called pollen-S) appears to determine the specific S-RNase from which a pollen tube accepts inhibition. The S-RNase gene and pollen-S segregate with the classically defined S-locus. The origin of a new specificity appears to require, at minimum, mutations in both genes. We explore the conditions under which new specificities may arise from an intermediate state of loss of self-recognition. Our evolutionary analysis of mutations that affect either pistil or pollen specificity indicates that natural selection favors mutations in pollen-S that reduce the set of pistils from which the pollen accepts inhibition and disfavors mutations in the S-RNase gene that cause the nonreciprocal acceptance of pollen specificities. We describe the range of parameters (rate of receipt of self-pollen and relative viability of inbred offspring) that permits the generation of a succession of new specificities. This evolutionary pathway begins with the partial breakdown of SI upon the appearance of a mutation in pollen-S that frees pollen from inhibition by any S-RNase presently in the population and ends with the restoration of SI by a mutation in the S-RNase gene that enables pistils to reject the new pollen type.
Minimum Requirements for the Function of Eukaryotic Translation Initiation Factor 2
Authors: Erickson F Les , Nika Joseph , Rippel Scott , Hannig Ernest M 
Published: April 2021

Abstract
Eukaryotic translation initiation factor 2 (eIF2) is a G protein heterotrimer required for GTP-dependent delivery of initiator tRNA to the ribosome. eIF2B, the nucleotide exchange factor for eIF2, is a heteropentamer that, in yeast, is encoded by four essential genes and one nonessential gene. We found that increased levels of wild-type eIF2, in the presence of sufficient levels of initiator tRNA, overcome the requirement for eIF2B in vivo. Consistent with bypassing eIF2B, these conditions also suppress the lethal effect of overexpressing the mammalian tumor suppressor PKR, an eIF2α kinase. The effects described are further enhanced in the presence of a mutation in the G protein (γ) subunit of eIF2, gcd11-K250R, which mimics the function of eIF2B in vitro. Interestingly, the same conditions that bypass eIF2B also overcome the requirement for the normally essential eIF2α structural gene (SUI2). Our results suggest that the eIF2βγ complex is capable of carrying out the essential function(s) of eIF2 in the absence of eIF2α and eIF2B and are consistent with the idea that the latter function primarily to regulate the level of eIF2·GTP·Met-tRNAiMet ternary complexes in vivo.
Genes Regulating Touch Cell Development in Caenorhabditis elegans
Authors: Du Hongping , Chalfie Martin 
Published: April 2021

Abstract
To identify genes regulating the development of the six touch receptor neurons, we screened the F2 progeny of mutated animals expressing an integrated mec-2::gfp transgene that is expressed mainly in these touch cells. From 2638 mutated haploid genomes, we obtained 11 mutations representing 11 genes that affected the production, migration, or outgrowth of the touch cells. Eight of these mutations were in known genes, and 2 defined new genes (mig-21 and vab-15). The mig-21 mutation is the first known to affect the asymmetry of the migrations of Q neuroblasts, the cells that give rise to two of the six touch cells. vab-15 is a msh-like homeobox gene that appears to be needed for the proper production of touch cell precursors, since vab-15 animals lacked the four more posterior touch cells. The remaining touch cells (the ALM cells) were present but mispositioned. A similar touch cell phenotype is produced by mutations in lin-32. A more severe phenotype; i.e., animals often lacked ALM cells, was seen in lin-32 vab-15 double mutants, suggesting that these genes acted redundantly in ALM differentiation. In addition to the touch cell abnormalities, vab-15 animals variably exhibit embryonic or larval lethality, cell degenerations, malformation of the posterior body, uncoordinated movement, and defective egg laying.
Interactions Between the Inositol 1,4,5-Trisphosphate and Cyclic AMP Signaling Pathways Regulate Larval Molting in Drosophila
Authors: Venkatesh K , Siddhartha G , Joshi Rohit , Patel Sonal , Hasan Gaiti 
Published: April 2021

Abstract
Larval molting in Drosophila, as in other insects, is initiated by the coordinated release of the steroid hormone ecdysone, in response to neural signals, at precise stages during development. In this study we have analyzed, using genetic and molecular methods, the roles played by two major signaling pathways in the regulation of larval molting in Drosophila. Previous studies have shown that mutants for the inositol 1,4,5-trisphosphate receptor gene (itpr) are larval lethals. In addition they exhibit delays in molting that can be rescued by exogenous feeding of 20-hydroxyecdysone. Here we show that mutants for adenylate cyclase (rut) synergize, during larval molting, with itpr mutant alleles, indicating that both cAMP and InsP3 signaling pathways function in this process. The two pathways act in parallel to affect molting, as judged by phenotypes obtained through expression of dominant negative and dominant active forms of protein kinase A (PKA) in tissues that normally express the InsP3 receptor. Furthermore, our studies predict the existence of feedback inhibition through protein kinase A on the InsP3 receptor by increased levels of 20-hydroxyecdysone.
Statistical Modeling of Interlocus Interactions in a Complex Disease: Rejection of the Multiplicative Model of Epistasis in Type 1 Diabetes
Authors: Cordell Heather J , Todd John A , Hill Natasha J , Lord Christopher J , Lyons Paul A , Peterson Laurence B , Wicker Linda S , Clayton David G 
Published: April 2021

AbstractIn general, common diseases do not follow a Mendelian inheritance pattern. To identify disease mechanisms and etiology, their genetic dissection may be assisted by evaluation of linkage in mouse models of human disease. Statistical modeling of multiple-locus linkage data from the nonobese diabetic (NOD) mouse model of type 1 diabetes has previously provided evidence for epistasis between alleles of several Idd (insulin-dependent diabetes) loci. The construction of NOD congenic strains containing selected segments of the diabetes-resistant strain genome allows analysis of the joint effects of alleles of different loci in isolation, without the complication of other segregating Idd loci. In this article, we analyze data from congenic strains carrying two chromosome intervals (a double congenic strain) for two pairs of loci: Idd3 and Idd10 and Idd3 and Idd5. The joint action of both pairs is consistent with models of additivity on either the log odds of the penetrance, or the liability scale, rather than with the previously proposed multiplicative model of epistasis. For Idd3 and Idd5 we would also not reject a model of additivity on the penetrance scale, which might indicate a disease model mediated by more than one pathway leading to β-cell destruction and development of diabetes. However, there has been confusion between different definitions of interaction or epistasis as used in the biological, statistical, epidemiological, and quantitative and human genetics fields. The degree to which statistical analyses can elucidate underlying biologic mechanisms may be limited and may require prior knowledge of the underlying etiology.
Identification and Characterization of a Polymorphic Receptor Kinase Gene Linked to the Self-Incompatibility Locus of Arabidopsis lyrata
Authors: Schierup Mikkel H , Mable Barbara K , Awadalla Philip , Charlesworth Deborah 
Published: April 2021

Abstract
We study the segregation of variants of a putative self-incompatibility gene in Arabidopsis lyrata. This gene encodes a sequence that is homologous to the protein encoded by the SRK gene involved in self-incompatibility in Brassica species. We show by diallel pollinations of plants in several full-sib families that seven different sequences of the gene in A. lyrata are linked to different S-alleles, and segregation analysis in further sibships shows that four other sequences behave as allelic to these. The family data on incompatibility provide evidence for dominance classes among the S-alleles, as expected for a sporophytic SI system. We observe no division into pollen-dominant and pollen-recessive classes of alleles as has been found in Brassica, but our alleles fall into at least three dominance classes in both pollen and stigma expression. The diversity among sequences of the A. lyrata putative S-alleles is greater than among the published Brassica SRK sequences, and, unlike Brassica, the alleles do not cluster into groups with similar dominance.
The Leucine-Rich Repeat Domain Can Determine Effective Interaction Between RPS2 and Other Host Factors in Arabidopsis RPS2-Mediated Disease Resistance
Authors: Banerjee Diya , Zhang Xiaochun , Bent Andrew F 
Published: April 2021

Abstract
Like many other plant disease resistance genes, Arabidopsis thaliana RPS2 encodes a product with nucleotide-binding site (NBS) and leucine-rich repeat (LRR) domains. This study explored the hypothesized interaction of RPS2 with other host factors that may be required for perception of Pseudomonas syringae pathogens that express avrRpt2 and/or for the subsequent induction of plant defense responses. Crosses between Arabidopsis ecotypes Col-0 (resistant) and Po-1 (susceptible) revealed segregation of more than one gene that controls resistance to P. syringae that express avrRpt2. Many F2 and F3 progeny exhibited intermediate resistance phenotypes. In addition to RPS2, at least one additional genetic interval associated with this defense response was identified and mapped using quantitative genetic methods. Further genetic and molecular genetic complementation experiments with cloned RPS2 alleles revealed that the Po-1 allele of RPS2 can function in a Col-0 genetic background, but not in a Po-1 background. The other resistance-determining genes of Po-1 can function, however, as they successfully conferred resistance in combination with the Col-0 allele of RPS2. Domain-swap experiments revealed that in RPS2, a polymorphism at six amino acids in the LRR region is responsible for this allele-specific ability to function with other host factors.
Multiple Functions of the Nonconserved N-Terminal Domain of Yeast TATA-Binding Protein
Authors: Lee Mark , Struhl Kevin 
Published: April 2021

Abstract
The TATA-binding protein (TBP) is composed of a highly conserved core domain sufficient for TATA-element binding and preinitiation complex formation as well as a highly divergent N-terminal region that is dispensable for yeast cell viability. In vitro, removal of the N-terminal region domain enhances TBP-TATA association and TBP dimerization. Here, we examine the effects of truncation of the N-terminal region in the context of yeast TBP mutants with specific defects in DNA binding and in interactions with various proteins. For a subset of mutations that disrupt DNA binding and the response to transcriptional activators, removal of the N-terminal domain rescues their transcriptional defects. By contrast, deletion of the N-terminal region is lethal in combination with mutations on a limited surface of TBP. Although this surface is important for interactions with TFIIA and Brf1, TBP interactions with these two factors do not appear to be responsible for this dependence on the N-terminal region. Our results suggest that the N-terminal region of TBP has at least two distinct functions in vivo. It inhibits the interaction of TBP with TATA elements, and it acts positively in combination with a specific region of the TBP core domain that presumably interacts with another protein(s).
Saccharomyces cerevisiae SMT4 Encodes an Evolutionarily Conserved Protease With a Role in Chromosome Condensation Regulation
Authors: Strunnikov Alexander V , Aravind L , Koonin Eugene V 
Published: April 2021

Abstract
In a search for regulatory genes affecting the targeting of the condensin complex to chromatin in Saccharomyces cerevisiae, we identified a member of the adenovirus protease family, SMT4. SMT4 overexpression suppresses the temperature-sensitive conditional lethal phenotype of smc2-6, but not smc2-8 or smc4-1. A disruption allele of SMT4 has a prominent chromosome phenotype: impaired targeting of Smc4p-GFP to rDNA chromatin. Site-specific mutagenesis of the predicted protease active site cysteine and histidine residues of Smt4p abolishes the SMT4 function in vivo. The previously uncharacterized SIZ1 (SAP and Miz) gene, which encodes a protein containing a predicted DNA-binding SAP module and a Miz finger, is identified as a bypass suppressor of the growth defect associated with the SMT4 disruption. The SIZ1 gene disruption is synthetically lethal with the SIZ2 deletion. We propose that SMT4, SIZ1, and SIZ2 are involved in a novel pathway of chromosome maintenance.