bluuebunny/crossref_metadata_2025_split huggingface dataset:
Yeast Nap1-Binding Protein Nbp2p Is Required for Mitotic Growth at High Temperatures and for Cell Wall Integrity
Authors: Ohkuni Kentaro , Okuda Asuko , Kikuchi Akihiko 
Published: April 2021

Abstract
Nbp2p is a Nap1-binding protein in Saccharomyces cerevisiae identified by its interaction with Nap1 by a two-hybrid system. NBP2 encodes a novel protein consisting of 236 amino acids with a Src homology 3 (SH3) domain. We showed that NBP2 functions to promote mitotic cell growth at high temperatures and cell wall integrity. Loss of Nbp2 results in cell death at high temperatures and in sensitivity to calcofluor white. Cell death at high temperature is thought not to be due to a weakened cell wall. Additionally, we have isolated several type-2C serine threonine protein phosphatases (PTCs) as multicopy suppressors and MAP kinase-kinase (MAPKK), related to the yeast PKC MAPK pathway, as deletion suppressors of the nbp2Δ mutant. Screening for deletion suppressors is a new genetic approach to identify and characterize additional proteins in the Nbp2-dependent pathway. Genetic analyses suggested that Ptc1, which interacts with Nbp2 by the two-hybrid system, acts downstream of Nbp2 and that cells lacking the function of Nbp2 prefer to lose Mkk1, but the PKC MAPK pathway itself is indispensable when Nbp2 is deleted at high temperature.
Allele Frequency-Based Analyses Robustly Map Sequence Sites Under Balancing Selection in a Malaria Vaccine Candidate Antigen
Authors: Polley Spencer D , Chokejindachai Watcharee , Conway David J 
Published: April 2021

Abstract
The Plasmodium falciparum apical membrane antigen 1 (AMA1) is a leading candidate for a malaria vaccine. Here, within-population analyses of alleles from 50 Thai P. falciparum isolates yield significant evidence for balancing selection on polymorphisms within the disulfide-bonded domains I and III of the surface accessible ectodomain of AMA1, a result very similar to that seen previously in a Nigerian population. Studying the frequency of nucleotide polymorphisms in both populations shows that the between-population component of variance (FST) is significantly lower in domains I and III compared to the intervening domain II and compared to 11 unlinked microsatellite loci. A nucleotide site-by-site analysis shows that sites with exceptionally high or low FST values cluster significantly into serial runs, with four runs of low values in domain I and one in domain III. These runs may map the sequences that are consistently under the strongest balancing selection from naturally acquired immune responses.
Genetic Analysis of the ADGF Multigene Family by Homologous Recombination and Gene Conversion in Drosophila
Authors: Dolezal Tomas , Gazi Michal , Zurovec Michal , Bryant Peter J 
Published: April 2021

Abstract
Many Drosophila genes exist as members of multigene families and within each family the members can be functionally redundant, making it difficult to identify them by classical mutagenesis techniques based on phenotypic screening. We have addressed this problem in a genetic analysis of a novel family of six adenosine deaminase-related growth factors (ADGFs). We used ends-in targeting to introduce mutations into five of the six ADGF genes, taking advantage of the fact that five of the family members are encoded by a three-gene cluster and a two-gene cluster. We used two targeting constructs to introduce loss-of-function mutations into all five genes, as well as to isolate different combinations of multiple mutations, independent of phenotypic consequences. The results show that (1) it is possible to use endsin targeting to disrupt gene clusters; (2) gene conversion, which is usually considered a complication in gene targeting, can be used to help recover different mutant combinations in a single screening procedure; (3) the reduction of duplication to a single copy by induction of a double-strand break is better explained by the single-strand annealing mechanism than by simple crossing over between repeats; and (4) loss of function of the most abundantly expressed family member (ADGF-A) leads to disintegration of the fat body and the development of melanotic tumors in mutant larvae.
Likelihood Analysis of Asymmetrical Mutation Bias Gradients in Vertebrate Mitochondrial Genomes
Authors: Faith Jeremiah J , Pollock David D 
Published: April 2021

AbstractProtein-coding genes in mitochondrial genomes have varying degrees of asymmetric skew in base frequencies at the third codon position. The variation in skew among genes appears to be caused by varying durations of time that the heavy strand spends in the mutagenic single-strand state during replication (DssH). The primary data used to study skew have been the gene-by-gene base frequencies in individual taxa, which provide little information on exactly what kinds of mutations are responsible for the base frequency skew. To assess the contribution of individual mutation components to the ancestral vertebrate substitution pattern, here we analyze a large data set of complete vertebrate mitochondrial genomes in a phylogeny-based likelihood context. This also allows us to evaluate the change in skew continuously along the mitochondrial genome and to directly estimate relative substitution rates. Our results indicate that different types of mutation respond differently to the DssH gradient. A primary role for hydrolytic deamination of cytosines in creating variance in skew among genes was not supported, but rather linearly increasing rates of mutation from adenine to hypoxanthine with DssH appear to drive regional differences in skew. Substitutions due to hydrolytic deamination of cytosines, although common, appear to quickly saturate, possibly due to stabilization by the mitochondrial DNA single-strand-binding protein. These results should form the basis of more realistic models of DNA and protein evolution in mitochondria.
An Ac -like Transposable Element Family With Transcriptionally Active Y-Linked Copies in the White Campion, Silene latifolia
Authors: Pritham Ellen J , Zhang Y Hi , Feschotte Cédric , Kesseli Rick V 
Published: April 2021

Abstract
An RFLP genomic subtraction was used to isolate male-specific sequences in the species Silene latifolia. One isolated fragment, SLP2, shares similarity to a portion of the Activator (Ac) transposase from Zea mays and to related proteins from other plant species. Southern blot analysis of male and female S. latifolia genomic DNA shows that SLP2 belongs to a low-copy-number repeat family with two Y-linked copies. Screening of a S. latifolia male genomic library using SLP2 as a probe led to the isolation of five clones, which were partially sequenced. One clone contains two large open reading frames that can be joined into a sequence encoding a putative protein of 682 amino acids by removing a short intron. Database searches and phylogenetic analysis show that this protein belongs to the hAT superfamily of transposases, closest to Tag2 (Arabidopsis thaliana), and contains all of the defined domains critical for the activity of these transposases. PCR with genomic and cDNA templates from S. latifolia male, female, and hermaphrodite individuals revealed that one of the Y-linked copies is transcriptionally active and alternatively spliced. This is the first report of a transcriptionally active transposable element (TE) family in S. latifolia and the first DNA transposon residing on a plant Y chromosome. The potential activity and regulation of this TE family and its use for Y chromosome gene discovery is discussed.
Distribution of Retroelements in Centromeres and Neocentromeres of Maize
Authors: Mroczek Rebecca J , Dawe R Kelly 
Published: April 2021

Abstract
Fluorescent in situ hybridization was used to examine the distribution of six abundant long terminal repeat (LTR) retroelements, Opie, Huck, Cinful-1, Prem-2/Ji, Grande, and Tekay/Prem-1 on maize pachytene chromosomes. Retroelement staining in euchromatin was remarkably uniform, even when we included the structurally polymorphic abnormal chromosome 10 (Ab10) in our analysis. This uniformity made it possible to use euchromatin as a control for quantitative staining intensity measurements in other regions of the genome. The data show that knobs, known to function as facultative neocentromeres when Ab10 is present, tend to exclude retroelements. A notable exception is Cinful-1, which accumulates in TR-1 knob arrays. Staining for each of the six retroelements was also substantially reduced in centromeric satellite arrays to an average of 30% of the staining in euchromatin. This contrasted with two previously described centromere-specific retrotransposable (CR) elements that were readily detected in centromeres. We suggest that retroelements are relatively rare in centromeres because they interrupt the long satellite arrays thought to be required for efficient centromere function. CR elements may have evolved mutualistic relationships with their plant hosts: they are known to interact with the kinetochore protein CENH3 and appear to accumulate in clusters, leaving long satellite arrays intact.
Duplication-Dependent CG Suppression of the Seed Storage Protein Genes of Maize
Authors: Lund Gertrud , Lauria Massimiliano , Guldberg Per , Zaina Silvio 
Published: April 2021

Abstract
This study investigates the prevalence of CG and CNG suppression in single- vs. multicopy DNA regions of the maize genome. The analysis includes the single- and multicopy seed storage proteins (zeins), the miniature inverted-repeat transposable elements (MITEs), and long terminal repeat (LTR) retrotransposons. Zein genes are clustered on specific chromosomal regions, whereas MITEs and LTRs are dispersed in the genome. The multicopy zein genes are CG suppressed and exhibit large variations in CG suppression. The variation observed correlates with the extent of duplication each zein gene has undergone, indicating that gene duplication results in an increased turnover of cytosine residues. Alignment of individual zein genes confirms this observation and demonstrates that CG depletion results primarily from polarized C:T and G:A transition mutations from a less to a more extensively duplicated gene. In addition, transition mutations occur primarily in a CG or CNG context suggesting that CG suppression may result from deamination of methylated cytosine residues. Duplication-dependent CG depletion is likely to occur at other loci as duplicated MITEs and LTR elements, or elements inserted into duplicated gene regions, also exhibit CG depletion.
High-Resolution Crossover Maps for Each Bivalent of Zea mays Using Recombination Nodules
Authors: Anderson Lorinda K , Doyle Gregory G , Brigham Brian , Carter Jenna , Hooker Kristina D , Lai Ann , Rice Mindy , Stack Stephen M 
Published: April 2021

Abstract
Recombination nodules (RNs) are closely correlated with crossing over, and, because they are observed by electron microscopy of synaptonemal complexes (SCs) in extended pachytene chromosomes, RNs provide the highest-resolution cytological marker currently available for defining the frequency and distribution of crossovers along the length of chromosomes. Using the maize inbred line KYS, we prepared an SC karyotype in which each SC was identified by relative length and arm ratio and related to the proper linkage group using inversion heterozygotes. We mapped 4267 RNs on 2080 identified SCs to produce high-resolution maps of RN frequency and distribution on each bivalent. RN frequencies are closely correlated with both chiasma frequencies and SC length. The total length of the RN recombination map is about twofold shorter than that of most maize linkage maps, but there is good correspondence between the relative lengths of the different maps when individual bivalents are considered. Each bivalent has a unique distribution of crossing over, but all bivalents share a high frequency of distal RNs and a severe reduction of RNs at and near kinetochores. The frequency of RNs at knobs is either similar to or higher than the average frequency of RNs along the SCs. These RN maps represent an independent measure of crossing over along maize bivalents.
Bayesian Model Choice and Search Strategies for Mapping Interacting Quantitative Trait Loci
Authors: Yi Nengjun , Xu Shizhong , Allison David B 
Published: April 2021

AbstractMost complex traits of animals, plants, and humans are influenced by multiple genetic and environmental factors. Interactions among multiple genes play fundamental roles in the genetic control and evolution of complex traits. Statistical modeling of interaction effects in quantitative trait loci (QTL) analysis must accommodate a very large number of potential genetic effects, which presents a major challenge to determining the genetic model with respect to the number of QTL, their positions, and their genetic effects. In this study, we use the methodology of Bayesian model and variable selection to develop strategies for identifying multiple QTL with complex epistatic patterns in experimental designs with two segregating genotypes. Specifically, we develop a reversible jump Markov chain Monte Carlo algorithm to determine the number of QTL and to select main and epistatic effects. With the proposed method, we can jointly infer the genetic model of a complex trait and the associated genetic parameters, including the number, positions, and main and epistatic effects of the identified QTL. Our method can map a large number of QTL with any combination of main and epistatic effects. Utility and flexibility of the method are demonstrated using both simulated data and a real data set. Sensitivity of posterior inference to prior specifications of the number and genetic effects of QTL is investigated.
Large-Scale Adaptive Hitchhiking Upon High Recombination in Drosophila simulans
Authors: Quesada Humberto , Ramírez Ursula E M , Rozas Julio , Aguadé Montserrat 
Published: April 2021

Abstract
Natural selection is expected to leave a characteristic footprint on neighboring nucleotide variation through the effects of genetic linkage. The size of the region affected is proportional to the strength of selection and greatly reduced with the recombinational distance from the selected site. Thus, the genomic footprint of selection is generally believed to be restricted to a small DNA stretch in normal and highly recombining regions. Here, we study the effect of selection on linked polymorphism (hitchhiking effect) by surveying nucleotide variation across a highly recombining ∼88-kb genomic fragment in an African population of Drosophila simulans. We find a core region of up to 38 kb with a major haplotype at intermediate frequency. The extended haplotype structure that gradually vanishes until disappearing is unusual for a highly recombining region. Both the presence in the structured genomic domain of a single major haplotype depleted of variability and the detected spatial pattern of variation along the ∼88-kb fragment are incompatible with neutral predictions in a panmictic population. A major role of demographic effects could also be discarded. The observed pattern of variation clearly provides evidence that directional selection has acted recently on this region, sweeping out variation around a strongly adaptive mutation. Our findings suggest a major role of positive selection in shaping DNA variability even in highly recombining regions.
The Sla2p Talin Domain Plays a Role in Endocytosis in Saccharomyces cerevisiae
Authors: Baggett Jennifer J , D'Aquino Katharine E , Wendland Beverly 
Published: April 2021

Abstract
Clathrin-binding adaptors play critical roles for endocytosis in multicellular organisms, but their roles in budding yeast have remained unclear. To address this question, we created a quadruple mutant yeast strain lacking the genes encoding the candidate clathrin adaptors Yap1801p, Yap1802p, and Ent2p and containing a truncated version of Ent1p, Ent1ΔCBMp, missing its clathrin-binding motif. This strain was viable and competent for endocytosis, suggesting the existence of other redundant adaptor-like factors. To identify these factors, we mutagenized the quadruple clathrin adaptor mutant strain and selected cells that were viable in the presence of full-length Ent1p, but inviable with only Ent1ΔCBMp; these strains were named Rcb (requires clathrin binding). One mutant strain, rcb432, contained a mutation in SLA2 that resulted in lower levels of a truncated protein lacking the F-actin binding talin homology domain. Analyses of this sla2 mutant showed that the talin homology domain is required for endocytosis at elevated temperature, that SLA2 exhibits genetic interactions with both ENT1 and ENT2, and that the clathrin adaptors and Sla2p together regulate the actin cytoskeleton and revealed conditions under which Yap1801p and Yap1802p contribute to viability. Together, our data support the view that Sla2p is an adaptor that links actin to clathrin and endocytosis.
Destabilizing Interactions Among [PSI +] and [PIN +] Yeast Prion Variants
Authors: Bradley Michael E , Liebman Susan W 
Published: April 2021

Abstract
The yeast Sup35 and Rnq1 proteins can exist in either the noninfectious soluble forms, [psi–]or[pin–], respectively, or the multiple infectious amyloid-like forms called [PSI+]or[PIN+] prion variants (or prion strains). It was previously shown that [PSI+] and [PIN+] prions enhance one another's de novo appearance. Here we show that specific prion variants of [PSI+] and [PIN+] disrupt each other's stable inheritance. Acquiring [PSI+] often impedes the inheritance of particular [PIN+] variants. Conversely, the presence of some [PIN+] variants impairs the inheritance of weak [PSI+] but not strong [PSI+] variants. These same [PIN+] variants generate a single-dot fluorescence pattern when a fusion of Rnq1 and green fluorescent protein is expressed. Another [PIN+] variant, which forms a distinctly different multiple-dot fluorescence pattern, does not impair [PSI+] inheritance. Thus, destabilization of prions by heterologous prions depends upon the variants involved. These findings may have implications for understanding interactions among other amyloid-forming proteins, including those associated with certain human diseases.
The pineapple eye Gene Is Required for Survival of Drosophila Imaginal Disc Cells
Authors: Shi Wei , Stampas Argyrios , Zapata Cynthia , Baker Nicholas E 
Published: April 2021

Abstract
Each ommatidium of the Drosophila eye is constructed by precisely 19 specified precursor cells, generated in part during a second mitotic wave of cell divisions that overlaps early stages of ommatidial cell specification. Homozygotes for the pineapple eye mutation lack sufficient precursor cells due to apoptosis during the period of fate specification. In addition development is delayed by apoptosis during earlier imaginal disc growth. Null alleles are recessive lethal and allelic to l(2)31Ek; heteroallelic combinations can show developmental delay, abnormal eye development, and reduced fertility. Mosaic clones autonomously show extensive cell death. The pineapple eye gene was identified and predicted to encode a novel 582-aminoacid protein. The protein contains a novel, cysteine-rich domain of 270 amino acids also found in predicted proteins of unknown function from other animals.
Germline Cell Death Is Inhibited by P-Element Insertions Disrupting the dcp-1/pita Nested Gene Pair in Drosophila
Authors: Laundrie Bonni , Peterson Jeanne S , Baum Jason S , Chang Jeffrey C , Fileppo Dana , Thompson Sharona R , McCall Kimberly 
Published: April 2021

Abstract
Germline cell death in Drosophila oogenesis is controlled by distinct signals. The death of nurse cells in late oogenesis is developmentally regulated, whereas the death of egg chambers during mid-oogenesis is induced by environmental stress or developmental abnormalities. P-element insertions in the caspase gene dcp-1 disrupt both dcp-1 and the outlying gene, pita, leading to lethality and defective nurse cell death in late oogenesis. By isolating single mutations in the two genes, we have found that the loss of both genes contributes to this ovary phenotype. Mutants of pita, which encodes a C2H2 zinc-finger protein, are homozygous lethal and show dumpless egg chambers and premature nurse cell death in germline clones. Early nurse cell death is not observed in the dcp-1/pita double mutants, suggesting that dcp-1+ activity is required for the mid-oogenesis cell death seen in pita mutants. dcp-1 mutants are viable and nurse cell death in late oogenesis occurs normally. However, starvation-induced germline cell death during mid-oogenesis is blocked, leading to a reduction and inappropriate nuclear localization of the active caspase Drice. These findings suggest that the combinatorial loss of pita and dcp-1 leads to the increased survival of abnormal egg chambers in mutants bearing the P-element alleles and that dcp-1 is essential for cell death during mid-oogenesis.
Age-Associated Activation of Epigenetically Repressed Genes in the Mouse
Authors: Bennett-Baker Pamela E , Wilkowski Jodi , Burke David T 
Published: April 2021

Abstract
Epigenetic control of gene expression is a consistent feature of differentiated mammalian cell types. Epigenetic expression patterns are mitotically heritable and are stably maintained in adult cells. However, unlike somatic DNA mutation, little is known about the occurrence of epigenetic change, or epimutation, during normal adult life. We have monitored the age-associated maintenance of two epigenetic systems—X inactivation and genomic imprinting—using the genes Atp7a and Igf2, respectively. Quantitative measurements of RNA transcripts from the inactive and active alleles were performed in mice from 2 to 24 months of age. For both genes, older animal cohorts showed reproducible increases in transcripts expressed from the silenced alleles. Loss of X chromosome silencing showed cohort mean increases of up to 2.2%, while imprinted-gene activation increased up to 6.7%. The results support the hypothesis that epigenetic loss of gene repression occurs in normal tissues and may be a contributing factor in progressive physiological dysfunction seen during mammalian aging. Quantitatively, the loss of epigenetic control may be one to two orders of magnitude greater than previously determined somatic DNA mutation.
Detection of New Quantitative Trait Loci for Susceptibility to Transmissible Spongiform Encephalopathies in Mice
Authors: Moreno Carole R , Lantier Frédéric , Lantier Isabelle , Sarradin Pierre , Elsen Jean-Michel 
Published: April 2021

Abstract
Susceptibility to scrapie is largely controlled by the PRNP gene in mice and in several other species. However, individuals with identical scrapie susceptibility Prnp alleles may have very different incubation periods, suggesting the influence of other environmental and genetic factors. To detect loci influencing susceptibility to TSE, two mouse lines carrying the same PRNP genotype (C57BL and RIII) were crossed to produce an F2 population inoculated intracerebrally with a mouse-adapted scrapie strain. Linkage was studied between 72 markers and the age of death of F2 animals. Six QTL were detected, two at a genome-wide significant level (chromosomes 5 and 7) and four at a genome-wide suggestive level (chromosomes 4, 6, 8, and 17). Our results confirmed the existence of some QTL that were detected previously (chromosomes 4, 6, 7, and 8) while others were found only in the present study (chromosomes 5 and 17). Furthermore, it seems that some QTL (chromosomes 4 and 8) are involved in resistance to scrapie as well as to BSE.