bluuebunny/crossref_metadata_2025_split huggingface dataset:
Locus-Specific Genetic Differentiation at Rw Among Warfarin-Resistant Rat (Rattus norvegicus) Populations
Authors: Kohn Michael H , Pelz Hans-Joachim , Wayne Robert K 
Published: April 2021

Abstract
Populations may diverge at fitness-related genes as a result of adaptation to local conditions. The ability to detect this divergence by marker-based genomic scans depends on the relative magnitudes of selection, recombination, and migration. We survey rat (Rattus norvegicus) populations to assess the effect that local selection with anticoagulant rodenticides has had on microsatellite marker variation and differentiation at the warfarin resistance gene (Rw) relative to the effect on the genomic background. Initially, using a small sample of 16 rats, we demonstrate tight linkage of microsatellite D1Rat219 to Rw by association mapping of genotypes expressing an anticoagulant-rodenticide-insensitive vitamin K 2,3-epoxide reductase (VKOR). Then, using allele frequencies at D1Rat219, we show that predicted and observed resistance levels in 27 populations correspond, suggesting intense and recent selection for resistance. A contrast of FST values between D1Rat219 and the genomic background revealed that rodenticide selection has overwhelmed drift-mediated population structure only at Rw. A case-controlled design distinguished these locus-specific effects of selection at Rw from background levels of differentiation more effectively than a population-controlled approach. Our results support the notion that an analysis of locus-specific population genetic structure may assist the discovery and mapping of novel candidate loci that are the object of selection or may provide supporting evidence for previously identified loci.
Identification of a Topoisomerase I Mutant, scsA1, as an Extragenic Suppressor of a Mutation in scaANBS1, the Apparent Homolog of Human Nibrin in Aspergillus nidulans
Authors: Fagundes Marcia R Z Kress , Fernandes Larissa , Savoldi Marcela , Harris Steven D , Goldman Maria H S , Goldman Gustavo H 
Published: April 2021

Abstract
The Mre11-Rad50-Nbs1 protein complex has emerged as a central player in the human cellular DNA damage response, and recent observations suggest that these proteins are at least partially responsible for the linking of DNA damage detection to DNA repair and cell cycle checkpoint functions. Mutations in scaANBS1, which encodes the apparent homolog of human nibrin in Aspergillus nidulans, inhibit growth in the presence of the antitopoisomerase I drug camptothecin. This article describes the selection and characterization of extragenic suppressors of the scaA1 mutation, with the aim of identifying other proteins that interfere with the pathway or complex in which the ScaA would normally be involved. Fifteen extragenic suppressors of the scaA1 mutation were isolated. The topoisomerase I gene can complement one of these suppressors. Synergistic interaction between the scaANBS1 and scsATOP1 genes in the presence of DNA-damaging agents was observed. Overexpression of topoisomerase I in the scaA1 mutant causes increased sensitivity to DNA-damaging agents. The scsATOP1 and the scaANBS1 gene products could functionally interact in pathways that either monitor or repair DNA double-strand breaks.
Rapid, Selective Digestion of Mitochondrial DNA in Accordance With the matA Hierarchy of Multiallelic Mating Types in the Mitochondrial Inheritance of Physarum polycephalum
Authors: Moriyama Y , Kawano S 
Published: April 2021

Abstract
Although mitochondria are inherited uniparentally in nearly all eukaryotes, the mechanism for this is unclear. When zygotes of the isogamous protist Physarum polycephalum were stained with DAPI, the fluorescence of mtDNA in half of the mitochondria decreased simultaneously to give small spots and then disappeared completely ∼1.5 hr after nuclear fusion, while the other mitochondrial nucleoids and all of the mitochondrial sheaths remained unchanged. PCR analysis of single zygote cells confirmed that the loss was limited to mtDNA from one parent. The vacant mitochondrial sheaths were gradually eliminated by 60 hr after mating. Using six mating types, the transmission patterns of mtDNA were examined in all possible crosses. In 39 of 60 crosses, strict uniparental inheritance was confirmed in accordance with a hierarchy of relative sexuality. In the other crosses, however, mtDNA from both parents was transmitted to plasmodia. The ratio of parental mtDNA was estimated to be from 1:1 to 1:10-4. Nevertheless, the matA hierarchy was followed. In these crosses, the mtDNA was incompletely digested, and mtDNA replicated during subsequent plasmodial development. We conclude that the rapid, selective digestion of mtDNA promotes the uniparental inheritance of mitochondria; when this fails, biparental inheritance occurs.
Molecular Markers for Rapidly Identifying Candidate Genes in Chlamydomonas reinhardtii: ERY1 and ERY2 Encode Chloroplast Ribosomal Proteins
Authors: Bowers Amber K , Keller Jennifer A , Dutcher Susan K 
Published: April 2021

Abstract
To take advantage of available expressed sequence tags and genomic sequence, we have developed 64 PCR-based molecular markers in Chlamydomonas reinhardtii that map to the 17 linkage groups. These markers will allow the rapid association of a candidate gene sequence with previously identified mutations. As proof of principle, we have identified the genes encoded by the ERY1 and ERY2 loci. Mendelian mutations that confer resistance to erythromycin define three unlinked nuclear loci in C. reinhardtii. Candidate genes ribosomal protein L4 (RPL4) and L22 (RPL22) are tightly linked to the ERY1 locus and ERY2 locus, respectively. Genomic DNA for RPL4 from wild type and five mutant ery1 alleles was amplified and sequenced and three different point mutations were found. Two different glycine residues (G102 and G112) are replaced by aspartic acid and both are in the unstructured region of RPL4 that lines the peptide exit tunnel of the chloroplast ribosome. The other two alleles change a splice site acceptor site. Genomic DNA for RPL22 from wild type and three mutant ery2 alleles was amplified and sequenced and revealed three different point mutations. Two alleles have premature stop codons and one allele changes a splice site acceptor site.
DNA Variation in a Conifer, Cryptomeria japonica (Cupressaceae sensu lato)
Authors: Kado Tomoyuki , Yoshimaru Hiroshi , Tsumura Yoshihiko , Tachida Hidenori 
Published: April 2021

Abstract
We investigated the nucleotide variation of a conifer, Cryptomeria japonica, and the divergence between this species and its closest relative, Taxodium distichum, at seven nuclear loci (Acl5, Chi1, Ferr, GapC, HemA, Lcyb, and Pat). Samples of C. japonica were collected from three areas, Kantou-Toukai, Hokuriku, and Iwate. No apparent geographic differentiation was found among these samples. However, the frequency spectrum of the nucleotide polymorphism revealed excesses of intermediate-frequency variants, which suggests that the population was not panmictic and a constant size in the past. The average nucleotide diversity, π, for silent sites was 0.00383. However, values of π for silent sites vary among loci. Comparisons of polymorphism to divergence among loci (the HKA test) showed that the polymorphism at the Acl5 locus was significantly lower. We also observed a nearly significant excess of replacement polymorphisms at the Lcyb locus. These results suggested possibilities of natural selection acting at some of the loci. Intragenic recombination was detected only once at the Chi1 locus and was not detected at the other loci. The low level of population recombination rate, 4Nr, seemed to be due to both low level of recombination, r, and small population size, N.
Combining Gene Expression and Molecular Marker Information for Mapping Complex Trait Genes: A Simulation Study
Authors: Pérez-Enciso Miguel , Toro Miguel A , Tenenhaus Michel , Gianola Daniel 
Published: April 2021

Abstract
A method for mapping complex trait genes using cDNA microarray and molecular marker data jointly is presented and illustrated via simulation. We introduce a novel approach for simulating phenotypes and genotypes conditionally on real, publicly available, microarray data. The model assumes an underlying continuous latent variable (liability) related to some measured cDNA expression levels. Partial least-squares logistic regression is used to estimate the liability under several scenarios where the level of gene interaction, the gene effect, and the number of cDNA levels affecting liability are varied. The results suggest that: (1) the usefulness of microarray data for gene mapping increases when both the number of cDNA levels in the underlying liability and the QTL effect decrease and when genes are coexpressed; (2) the correlation between estimated and true liability is large, at least under our simulation settings; (3) it is unlikely that cDNA clones identified as significant with partial least squares (or with some other technique) are the true responsible cDNAs, especially as the number of clones in the liability increases; (4) the number of putatively significant cDNA levels increases critically if cDNAs are coexpressed in a cluster (however, the proportion of true causal cDNAs within the significant ones is similar to that in a no-coexpression scenario); and (5) data reduction is needed to smooth out the variability encountered in expression levels when these are analyzed individually.
High-Resolution Mapping of Quantitative Trait Loci by Selective Recombinant Genotyping
Authors: Ronin Y , Korol A , Shtemberg M , Nevo E , Soller M 
Published: April 2021

Abstract
Selective recombinant genotyping (SRG) is a three-stage procedure for high-resolution mapping of a QTL that has previously been mapped to a known confidence interval (target C.I.). In stage 1, a large mapping population is accessed and phenotyped, and a proportion, P, of the high and low tails is selected. In stage 2, the selected individuals are genotyped for a pair of markers flanking the target C.I., and a group of R individuals carrying recombinant chromosomes in the target interval are identified. In stage 3, the recombinant individuals are genotyped for a set of M markers spanning the target C.I. Extensive simulations showed that: (1) Standard error of QTL location (SEQTL) decreased when QTL effect (d) or population size (N) increased, but was constant for given “power factor” (PF = d2N); (2) increasing the proportion selected in the tails beyond 0.25 had only a negligible effect on SEQTL; and (3) marker spacing in the target interval had a remarkably powerful effect on SEQTL, yielding a reduction of up to 10-fold in going from highest (24 cM) to lowest (0.29 cM) spacing at given population size and QTL effect. At the densest marker spacing, SEQTL of 1.0-0.06 cM were obtained at PF = 500-16,000. Two new genotyping procedures, the half-section algorithm and the golden section/half-section algorithm, allow the equivalent of complete haplotyping of the target C.I. in the recombinant individuals to be achieved with many fewer data points than would be required by complete individual genotyping.
Estimating the Time Since the Fixation of a Beneficial Allele
Authors: Przeworski Molly 
Published: April 2021

Abstract
The fixation of a beneficial allele in a population leaves a well-characterized signature in patterns of nucleotide variation at linked sites. This signature can be used to estimate the time since fixation from patterns of polymorphism in extant individuals. I introduce a method to assess the support in polymorphism data for a recent episode of directional positive selection and to estimate the time since fixation. I summarize the polymorphism data by three statistics that carry information about levels of diversity, the allele frequency spectrum, and the extent of allelic associations. Simulations are then used to obtain a sample from the posterior distribution of the time since fixation, conditional on the observed summaries. I test the performance of the approach on simulated data and apply it to the gene tb1 in maize. The data support the recent fixation of a favored allele, consistent with what is known about the importance of tb1 in the domestication process of maize.
The AF-6 Homolog Canoe Acts as a Rap1 Effector During Dorsal Closure of the Drosophila Embryo
Authors: Boettner Benjamin , Harjes Phoebe , Ishimaru Satoshi , Heke Michael , Fan Hong Qing , Qin Yi , Van Aelst Linda , Gaul Ulrike 
Published: April 2021

Abstract
Rap1 belongs to the highly conserved Ras subfamily of small GTPases. In Drosophila, Rap1 plays a critical role in many different morphogenetic processes, but the molecular mechanisms executing its function are unknown. Here, we demonstrate that Canoe (Cno), the Drosophila homolog of mammalian junctional protein AF-6, acts as an effector of Rap1 in vivo. Cno binds to the activated form of Rap1 in a yeast two-hybrid assay, the two molecules colocalize to the adherens junction, and they display very similar phenotypes in embryonic dorsal closure (DC), a process that relies on the elongation and migration of epithelial cell sheets. Genetic interaction experiments show that Rap1 and Cno act in the same molecular pathway during DC and that the function of both molecules in DC depends on their ability to interact. We further show that Rap1 acts upstream of Cno, but that Rap1, unlike Cno, is not involved in the stimulation of JNK pathway activity, indicating that Cno has both a Rap1-dependent and a Rap1-independent function in the DC process.
DNA Methylation in Placentas of Interspecies Mouse Hybrids
Authors: Schütt Sabine , Florl Andrea R , Shi Wei , Hemberger Myriam , Orth Annie , Otto Sabine , Schulz Wolfgang A , Fundele Reinald H 
Published: April 2021

Abstract
Interspecific hybridization in the genus Mus results in several hybrid dysgenesis effects, such as male sterility and X-linked placental dysplasia (IHPD). The genetic or molecular basis for the placental phenotypes is at present not clear. However, an extremely complex genetic system that has been hypothesized to be caused by major epigenetic changes on the X chromosome has been shown to be active. We have investigated DNA methylation of several single genes, Atrx, Esx1, Mecp2, Pem, Psx1, Vbp1, Pou3f4, and Cdx2, and, in addition, of LINE-1 and IAP repeat sequences, in placentas and tissues of fetal day 18 mouse interspecific hybrids. Our results show some tendency toward hypomethylation in the late gestation mouse placenta. However, no differential methylation was observed in hyper- and hypoplastic hybrid placentas when compared with normal-sized littermate placentas or intraspecific Mus musculus placentas of the same developmental stage. Thus, our results strongly suggest that generalized changes in methylation patterns do not occur in trophoblast cells of such hybrids.
Identification of Cis-regulatory Elements in the Mouse Pax9/Nkx2-9 Genomic Region: Implication for Evolutionary Conserved Synteny
Authors: Santagati Fabio , Abe Kuniya , Schmidt Volker , Schmitt-John Thomas , Suzuki Misao , Yamamura Ken-ichi , Imai Kenji 
Published: April 2021

Abstract
We previously reported close physical linkage between Pax9 and Nkx2-9 in the human, mouse, and pufferfish (Fugu rubripes) genomes. In this study, we analyzed cis-regulatory elements of the two genes by comparative sequencing in the three species and by transgenesis in the mouse. We identified two regions including conserved noncoding sequences that possessed specific enhancer activities for expression of Pax9 in the medial nasal process and of Nkx2-9 in the ventral neural tube. Remarkably, the latter contained the consensus Gli-binding motif. Interestingly, the identified Pax9 cis-regulatory sequences were located in an intron of the neighboring gene Slc25a21. Close examination of an extended genomic interval around Pax9 revealed the presence of strong synteny conservation in the human, mouse, and Fugu genomes. We propose such an intersecting organization of cis-regulatory sequences in multigenic regions as a possible mechanism that maintains evolutionary conserved synteny.
Heterogeneous Selection at Specific Loci in Natural Environments in Arabidopsis thaliana
Authors: Weinig Cynthia , Dorn Lisa A , Kane Nolan C , German Zachary M , Halldorsdottir Solveig S , Ungerer Mark C , Toyonaga Yuko , Mackay Trudy F C , Purugganan Michael D , Schmitt Johanna 
Published: April 2021

Abstract
Genetic variation for quantitative traits is often greater than that expected to be maintained by mutation in the face of purifying natural selection. One possible explanation for this observed variation is the action of heterogeneous natural selection in the wild. Here we report that selection on quantitative trait loci (QTL) for fitness traits in the model plant species Arabidopsis thaliana differs among natural ecological settings and genetic backgrounds. At one QTL, the allele that enhanced the viability of fall-germinating seedlings in North Carolina reduced the fecundity of spring-germinating seedlings in Rhode Island. Several other QTL experienced strong directional selection, but only in one site and seasonal cohort. Thus, different loci were exposed to selection in different natural environments. Selection on allelic variation also depended upon the genetic background. The allelic fitness effects of two QTL reversed direction depending on the genotype at the other locus. Moreover, alternative alleles at each of these loci caused reversals in the allelic fitness effects of a QTL closely linked to TFL1, a candidate developmental gene displaying nucleotide sequence polymorphism consistent with balancing selection. Thus, both environmental heterogeneity and epistatic selection may maintain genetic variation for fitness in wild plant species.
Post-transcriptional Cosuppression of Ty1 Retrotransposition
Authors: Garfinkel David J , Nyswaner Katherine , Wang Jun , Cho Jae-Yong 
Published: April 2021

Abstract
To determine whether homology-dependent gene silencing or cosuppression mechanisms underlie copy number control (CNC) of Ty1 retrotransposition, we introduced an active Ty1 element into a naïve strain. Single Ty1 element retrotransposition was elevated in a Ty1-less background, but decreased dramatically when additional elements were present. Transcription from the suppressing Ty1 elements enhanced CNC but translation or reverse transcription was not required. Ty1 CNC occurred with a transcriptionally active Ty2 element, but not with Ty3 or Ty5 elements. CNC also occurred when the suppressing Ty1 elements were transcriptionally silenced, fused to the constitutive PGK1 promoter, or contained a minimal segment of mostly TYA1-gag sequence. Ty1 transcription of a multicopy element expressed from the GAL1 promoter abolished CNC, even when the suppressing element was defective for transposition. Although Ty1 RNA and TyA1-gag protein levels increased with the copy number of expressible elements, a given element's transcript level varied less than twofold regardless of whether the suppressing elements were transcriptionally active or repressed. Furthermore, a decrease in the synthesis of Ty1 cDNA is strongly associated with Ty1 CNC. Together our results suggest that Ty1 cosuppression can occur post-transcriptionally, either prior to or during reverse transcription.
The Role of Cdh1p in Maintaining Genomic Stability in Budding Yeast
Authors: Ross Karen E , Cohen-Fix Orna 
Published: April 2021

Abstract
Cdh1p, a substrate specificity factor for the cell cycle-regulated ubiquitin ligase, the anaphase-promoting complex/cyclosome (APC/C), promotes exit from mitosis by directing the degradation of a number of proteins, including the mitotic cyclins. Here we present evidence that Cdh1p activity at the M/G1 transition is important not only for mitotic exit but also for high-fidelity chromosome segregation in the subsequent cell cycle. CDH1 showed genetic interactions with MAD2 and PDS1, genes encoding components of the mitotic spindle assembly checkpoint that acts at metaphase to prevent premature chromosome segregation. Unlike cdh1Δ and mad2Δ single mutants, the mad2Δ cdh1Δ double mutant grew slowly and exhibited high rates of chromosome and plasmid loss. Simultaneous deletion of PDS1 and CDH1 caused extensive chromosome missegregation and cell death. Our data suggest that at least part of the chromosome loss can be attributed to kinetochore/spindle problems. Our data further suggest that Cdh1p and Sic1p, a Cdc28p/Clb inhibitor, have overlapping as well as nonoverlapping roles in ensuring proper chromosome segregation. The severe growth defects of both mad2Δ cdh1Δ and pds1Δ cdh1Δ strains were rescued by overexpressing Swe1p, a G2/M inhibitor of the cyclin-dependent kinase, Cdc28p/Clb. We propose that the failure to degrade cyclins at the end of mitosis leaves cdh1Δ mutant strains with abnormal Cdc28p/Clb activity that interferes with proper chromosome segregation.
The Promotion of Gonadal Cell Divisions by the Caenorhabditis elegans TRPM Cation Channel GON-2 Is Antagonized by GEM-4 Copine
Authors: Church Diane L , Lambie Eric J 
Published: April 2021

Abstract
The initiation of postembryonic cell divisions by the gonadal precursors of C. elegans requires the activity of gon-2. gon-2 encodes a predicted cation channel (GON-2) of the TRPM subfamily of TRP proteins and is likely to mediate the influx of Ca2+ and/or Mg2+. We report here that mutations in gem-4 (gon-2 extragenic modifier) are capable of suppressing loss-of-function alleles of gon-2. gem-4 encodes a member of the copine family of Ca2+-dependent phosphatidylserine binding proteins. Overall, our data indicate that GEM-4 antagonizes GON-2. This antagonism could be mediated by a direct inhibition of GON-2 by GEM-4, since both proteins are predicted to be localized to the plasma membrane. Alternatively, GEM-4 could affect GON-2 activity levels by either promoting endocytosis or inhibiting exocytosis of vesicles that carry GON-2. It is also possible that GEM-4 and GON-2 act in parallel to each other. Mutation of gem-4 does not suppress the gonadal defects produced by inactivation of gon-4, suggesting that gon-4 either acts downstream of gem-4 and gon-2 or acts in a parallel regulatory pathway.
A Family of Genes Clustered at the Triplo-lethal Locus of Drosophila melanogaster Has an Unusual Evolutionary History and Significant Synteny With Anopheles gambiae
Authors: Dorer Douglas R , Rudnick Jamie A , Moriyama Etsuko N , Christensen Alan C 
Published: April 2021

Abstract
Within the unique Triplo-lethal region (Tpl) of the Drosophila melanogaster genome we have found a cluster of 20 genes encoding a novel family of proteins. This family is also present in the Anopheles gambiae genome and displays remarkable synteny and sequence conservation with the Drosophila cluster. The family is also present in the sequenced genome of D. pseudoobscura, and homologs have been found in Aedes aegypti mosquitoes and in four other insect orders, but it is not present in the sequenced genome of any noninsect species. Phylogenetic analysis suggests that the cluster evolved prior to the divergence of Drosophila and Anopheles (250 MYA) and has been highly conserved since. The ratio of synonymous to nonsynonymous substitutions and the high codon bias suggest that there has been selection on this family both for expression level and function. We hypothesize that this gene family is Tpl, name it the Osiris family, and consider possible functions. We also predict that this family of proteins, due to the unique dosage sensitivity and the lack of homologs in noninsect species, would be a good target for genetic engineering or novel insecticides.
A Function for Subtelomeric DNA in Saccharomyces cerevisiae
Authors: Barton Arnold B , Su Yuping , Lamb Jacque , Barber Dianna , Kaback David B 
Published: April 2021

Abstract
The subtelomeric DNA sequences from chromosome I of Saccharomyces cerevisiae are shown to be inherently poor substrates for meiotic recombination. On the basis of these results and prior observations that crossovers near telomeres do not promote efficient meiosis I segregation, we suggest that subtelomeric sequences evolved to prevent recombination from occurring where it cannot promote efficient segregation.