bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recombination Enhancement by Replication (RER) in Rhizobium etli
Authors: Valencia-Morales Edgar , Romero David 
Published: April 2021

Abstract
Studies in several organisms show that recombination and replication interact closely. Recombinational repair usually requires associated replication at some stage; moreover, additional replication can induce recombination through either homologous or illegitimate events. In prokaryotes, stimulation of recombination by replication is more dramatic when rolling circle replication is employed. In contrast, θ-type replication induces only a modest increase in recombination frequency. In this article, we show that induction of θ-type replication from a supernumerary origin in the symbiotic plasmid (pSym) of Rhizobium etli leads to a 1000-fold increase in deletion formation on this plasmid. These deletions span 120 kb (the symbiotic region) and have as endpoints the reiterated nitrogenase operons. We have named this phenomenon RER, for recombination enhancement by replication. RER is not affected by the position of the replication origin in the pSym, the direction of advance of the replication fork, or the distance from the origin to the recombining repeats. On the other hand, RER is dependent on an active recA allele, indicating that it is due to homologous recombination. RER displays a strong regionality restricted to the symbiotic region. The similarities and differences of RER with the recombination process observed at the terminus of replication of the Escherichia coli chromosome are discussed.
Estimating Recombinational Parameters in Streptococcus pneumoniae From Multilocus Sequence Typing Data
Authors: Feil Edward J , Smith John Maynard , Enright Mark C , Spratt Brian G 
Published: April 2021

Abstract
Multilocus sequence typing (MLST) is a highly discriminatory molecular typing method that defines isolates of bacterial pathogens using the sequences of ~450-bp internal fragments of seven housekeeping genes. This technique has been applied to 575 isolates of Streptococcus pneumoniae and identifies a number of discrete clonal complexes. These clonal complexes are typically represented by a single group of isolates sharing identical alleles at all seven loci, plus single-locus variants that differ from this group at only one out of the seven loci. As MLST is highly discriminatory, the members of each clonal complex can be assumed to have a recent common ancestor, and the molecular events that give rise to the single-locus variants can be used to estimate the relative contributions of recombination and mutation to clonal divergence. By comparing the sequences of the variant alleles within each clonal complex with the allele typically found within that clonal complex, we estimate that recombination has generated new alleles at a frequency ~10-fold higher than mutation, and that a single nucleotide site is ~50 times more likely to change through recombination than mutation. We also demonstrate how to estimate the average length of recombinational replacements from MLST data.
A Role for the Noncatalytic N Terminus in the Function of Cdc25, a Saccharomyces cerevisiae Ras-Guanine Nucleotide Exchange Factor
Authors: Chen Reneé A , Michaeli Tamer , Van Aelst Linda , Ballester Roymarie 
Published: April 2021

Abstract
The Saccharomyces cerevisiae CDC25 gene encodes a guanine nucleotide exchange factor (GEF) for Ras proteins. Its catalytic domain is highly homologous to Ras-GEFs from all eukaryotes. Even though Cdc25 is the first Ras-GEF identified in any organism, we still know very little about how its function is regulated in yeast. In this work we provide evidence for the involvement of the N terminus of Cdc25 in the regulation of its activity. A truncated CDC25 lacking the noncatalytic C-terminal coding sequence was identified in a screen of high-copy suppressors of the heat-shock-sensitive phenotype of strains in which the Ras pathway is hyper-activated. The truncated gene acts as a dominant-negative mutant because it only suppresses the heat-shock sensitivity of strains that require the function of CDC25. Our two-hybrid assays and immunoprecipitation analyses show interactions between the N terminus of Cdc25 and itself, the C terminus, and the full-length protein. These results suggest that the dominant-negative effect may be a result of oligomerization with endogenous Cdc25. Further evidence of the role of the N terminus of Cdc25 in the regulation of its activity is provided by the mapping of the activating mutation of CDC25HS20 to the serine residue at position 365 in the noncatalytic N-terminal domain. This mutation induces a phenotype similar to activating mutants of other genes in the Ras pathway in yeast. Hence, the N terminus may exert a negative control on the catalytic activity of the protein. Taken together these results suggest that the N terminus plays a crucial role in regulating Cdc25 and consequently Ras activity, which in S. cerevisiae is essential for cell cycle progression.
Glucose and Ras Activity Influence the Ubiquitin Ligases APC/C and SCF in Saccharomyces cerevisiae
Authors: Irniger Stefan , Bäumer Matthias , Braus Gerhard H 
Published: April 2021

Abstract
In budding yeast, the Ras/cAMP pathway is involved in the coordination of cell growth and cell division. Glucose-rich medium stimulates Ras/cAMP signaling, which causes an increase in the critical cell size for cell cycle entry. Here we show that glucose and activated Ras proteins also influence the function of the anaphase-promoting complex (APC/C), a ubiquitin-protein ligase required for sister chromatid separation and mitotic exit. We found that apc10-22 and other mutants defective in the APC/C are suppressed by reduced Ras signaling activity, by a deletion of the RAS2 gene, by a cdc25 mutation, by elevated levels of PDE2, or by growth without glucose. Viability of these mutants is also enhanced by decreased Cdk1 activity. In contrast, a constitutively activated RAS2Val19 allele or shifts to glucose medium are deleterious to apc10-22 mutants. Remarkably, cdc34-2 mutants, which are impaired in SCF function, are differently affected with respect to Ras activity. Viability of cdc34-2 mutants at elevated temperatures is dependent on glucose and the RAS2 gene. We conclude that glucose and Ras proteins influence the APC/C and the SCF complex in an opposite manner. These ubiquitin ligases might represent novel targets for modulating cell division in response to growth conditions.
RAD51 Is Required for Propagation of the Germinal Nucleus in Tetrahymena thermophila
Authors: Marsh Thomas C , Cole Eric S , Stuart Kathleen R , Campbell Colin , Romero Daniel P 
Published: April 2021

Abstract
RAD51, the eukaryote homolog of the Escherichia coli recA recombinase, participates in homologous recombination during mitosis, meiosis, and in the repair of double-stranded DNA breaks. The Tetrahymena thermophila RAD51 gene was recently cloned, and the in vitro activities and induction of Rad51p following DNA damage were shown to be similar to that of RAD51 from other species. This study describes the pattern of Tetrahymena RAD51 expression during both the cell cycle and conjugation. Tetrahymena RAD51 mRNA abundance is elevated during macronuclear S phase during vegetative cell growth and with both meiotic prophase and new macronuclear development during conjugation. Gene disruption of the macronuclear RAD51 locus leads to severe abnormalities during both vegetative growth and conjugation. rad51 nulls divide slowly and incur rapid deterioration of their micronuclear chromosomes. Conjugation of two rad51 nulls leads to an arrest early during prezygotic development (meiosis I). We discuss the potential usefulness of the ciliates' characteristic nuclear duality for further analyses of the potentially unique roles of Tetrahymena RAD51.
Dominance, Epistasis and the Genetics of Postzygotic Isolation
Authors: Turelli Michael , Orr H Allen 
Published: April 2021

AbstractThe sterility and inviability of species hybrids can be explained by between-locus “Dobzhansky-Muller” incompatibilities: alleles that are fit on their “normal” genetic backgrounds sometimes lower fitness when brought together in hybrids. We present a model of two-locus incompatibilities that distinguishes among three types of hybrid interactions: those between heterozygous loci (H0), those between a heterozygous and a homozygous (or hemizygous) locus (H1), and those between homozygous loci (H2). We predict the relative fitnesses of hybrid genotypes by calculating the expected numbers of each type of incompatibility. We use this model to study Haldane's rule and the large effect of X chromosomes on postzygotic isolation. We show that the severity of H0 vs. H1 incompatibilities is key to understanding Haldane's rule, while the severity of H1 vs. H2 incompatibilities must also be considered to explain large X effects. Large X effects are not inevitable in backcross analyses but rather—like Haldane's rule—may often reflect the recessivity of alleles causing postzygotic isolation. We also consider incompatibilities involving the Y (or W) chromosome and maternal effects. Such incompatibilities are common in Drosophila species crosses, and their consequences in male- vs. female-heterogametic taxa may explain the pattern of exceptions to Haldane's rule.
Molecular Variation at the In(2L)t Proximal Breakpoint Site in Natural Populations of Drosophila melanogaster and D. simulans
Authors: Andolfatto Peter , Kreitman Martin 
Published: April 2021

Abstract
A previous study of nucleotide polymorphism in a Costa Rican population of Drosophila melanogaster found evidence for a nonneutral deficiency in the number of haplotypes near the proximal breakpoint of In(2L)t, a common inversion polymorphism in this species. Another striking feature of the data was a window of unusually high nucleotide diversity spanning the breakpoint site. To distinguish between selective and neutral demographic explanations for the observed patterns in the data, we sample alleles from three additional populations of D. melanogaster and one population of D. simulans. We find that the strength of associations among sites found at the breakpoint varies between populations of D. melanogaster. In D. simulans, analysis of the homologous region reveals unusually elevated levels of nucleotide polymorphism spanning the breakpoint site. As with American populations of D. melanogaster, our D. simulans sample shows a marked reduction in the number of haplotypes but not in nucleotide diversity. Haplotype tests reveal a significant deficiency in the number of haplotypes relative to the neutral expectation in the D. simulans sample and some populations of D. melanogaster. At the breakpoint site, the level of divergence between haplotype classes is comparable to interspecific divergence. The observation of interspecific polymorphisms that differentiate major haplotype classes in both species suggests that haplotype classes at this locus are considerably old. When considered in the context of other studies on patterns of variation within and between populations of D. melanogaster and D. simulans, our data appear more consistent with the operation of selection than with simple demographic explanations.
Two Genes Required for Meiotic Recombination in Drosophila Are Expressed From a Dicistronic Message
Authors: Liu H , Jang J K , Graham J , Nycz K , McKim K S 
Published: April 2021

Abstract
We have isolated two alleles of a previously unidentified meiotic recombination gene, mei-217. Genetic analysis of these mutants shows that mei-217 is a typical “precondition” gene. The phenotypes of the mutants are meiosis specific. The strongest allele has &lt;10% of the normal level of crossing over, and the residual events are distributed abnormally. We have used double mutant analysis to position mei-217 in the meiotic recombination pathway. In general, mutations causing defects in the initiation of meiotic recombination are epistatic to mutations in mei-41 and spnB. These two mutations, however, are epistatic to mei-217, suggesting that recombination is initiated normally in mei-217 mutants. It is likely that mei-217 mutants are able to make Holliday junction intermediates but are defective in the production of crossovers. These phenotypes are most similar to mutants of the mei-218 gene. This is striking because mei-217 and mei-218 are part of the same transcription unit and are most likely produced from a dicistronic message.
Bias and Sampling Error of the Estimated Proportion of Genotypic Variance Explained by Quantitative Trait Loci Determined From Experimental Data in Maize Using Cross Validation and Validation With Independent Samples
Authors: Utz H Friedrich , Melchinger Albrecht E , Schön Chris C 
Published: April 2021

Abstract
Cross validation (CV) was used to analyze the effects of different environments and different genotypic samples on estimates of the proportion of genotypic variance explained by QTL (p). Testcrosses of 344 F3 maize lines grown in four environments were evaluated for a number of agronomic traits. In each of 200 replicated CV runs, this data set was subdivided into an estimation set (ES) and various test sets (TS). ES were used to map QTL and estimate p for each run (p^ES) and its median (p~ES) across all runs. The bias of these estimates was assessed by comparison with the median (p~IS.ES) obtained from TS. We also used two independent validation samples derived from the same cross for further comparison. The median p~ES showed a large upward bias compared to p~TS.ES. Environmental sampling generally had a smaller effect on the bias of p~ES than genotypic sampling or both factors simultaneously. In independent validation, p~TS.ES was on average only 50% of p~ES. A wide range among p^ES reflected a large sampling error of these estimates. QTL frequency distributions and comparison of estimated QTL effects indicated a low precision of QTL localization and an upward bias in the absolute values of estimated QTL effects from ES. CV with data from three QTL studies reported in the literature yielded similar results as those obtained with maize testcrosses. We therefore recommend CV for obtaining asymptotically unbiased estimates of p and consequently a realistic assessment of the prospects of MAS.
Genetic Parentage in Large Half-Sib Clutches: Theoretical Estimates and Empirical Appraisals
Authors: DeWoody J Andrew , Walker DeEtte , Avise John C 
Published: April 2021

Abstract
Nearly all of the 906 embryos from a male-tended nest of the sand goby (Pomatoschistus minutus) were genotyped at two hypervariable microsatellite loci to document conclusively the number of mothers and their relative genetic contributions to the nest. The true number of mothers determined by this nearly exhaustive genetic appraisal was compared to computer simulation treatments based on allele frequencies in the population, assumptions about reproductive skew, and statistical sampling strategies of progeny subsets. The “ground-truthed” appraisal and the theoretical estimates showed good agreement, indicating that for this nest a random sample of ~20 offspring would have sufficed for assessing the true number of biological parents (but not necessarily their relative genetic contributions). Also, a general dilocus matrix procedure is suggested for organizing and interpreting otherwise cumbersome data sets when extremely large numbers of full-sib and half-sib embryos from a nest are genotyped at two or more hypervariable loci.
Comparative Genetics of Nucleotide Binding Site-Leucine Rich Repeat Resistance Gene Homologues in the Genomes of Two Dicotyledons: Tomato and Arabidopsis
Authors: Pan Qilin , Liu Yong-Sheng , Budai-Hadrian Ofra , Sela Marianne , Carmel-Goren Lea , Zamir Dani , Fluhr Robert 
Published: April 2021

Abstract
The presence of a single resistance (R) gene allele can determine plant disease resistance. The protein products of such genes may act as receptors that specifically interact with pathogen-derived factors. Most functionally defined R-genes are of the nucleotide binding site-leucine rich repeat (NBS-LRR) supergene family and are present as large multigene families. The specificity of R-gene interactions together with the robustness of plant-pathogen interactions raises the question of their gene number and diversity in the genome. Genomic sequences from tomato showing significant homology to genes conferring race-specific resistance to pathogens were identified by systematically “scanning” the genome using a variety of primer pairs based on ubiquitous NBS motifs. Over 70 sequences were isolated and 10% are putative pseudogenes. Mapping of the amplified sequences on the tomato genetic map revealed their organization as mixed clusters of R-gene homologues that showed in many cases linkage to genetically characterized tomato resistance loci. Interspecific examination within Lycopersicon showed the existence of a null allele. Consideration of the tomato and potato comparative genetic maps unveiled conserved syntenic positions of R-gene homologues. Phylogenetic clustering of R-gene homologues within tomato and other Solanaceae family members was observed but not with R-gene homologues from Arabidopsis thaliana. Our data indicate remarkably rapid evolution of R-gene homologues during diversification of plant families.
The Murky Origin of Snow White and Her T-Even Dwarfs
Authors: Abedon Stephen T 
Published: April 2021

AbstractThat two distinct kinds of substances—the d'Hérelle substances and the genes—should both possess this most remarkable property of heritable variation or “mutability,” each working by a totally different mechanism, is quite conceivable, considering the complexity of protoplasm, yet it would seem a curious coincidence indeed. It would open up the possibility of two totally different kinds of life, working by different mechanisms. On the other hand, if these d'Hérelle bodies were really genes, fundamentally like our chromosome genes, they would give us an utterly new angle from which to attack the gene problem. They are filterable, to some extent isolable, can be handled in test-tubes, and their properties, as shown by their effects on the bacteria, can then be studied after treatment. It would be very rash to call these bodies genes, and yet at present we must confess that there is no distinction known between the genes and them. Hence we cannot categorically deny that perhaps we may be able to grind genes in a mortar and cook them in a beaker after all. Must we geneticists become bacteriologists, physiological chemists, and physicists, simultaneously with being zoologists and botanists? Let us hope so.H. J. Muller (1922, pp. 48–49)
Multiple Genetic Pathways for Restarting DNA Replication Forks in Escherichia coli K-12
Authors: Sandler Steven J 
Published: April 2021

Abstract
In Escherichia coli, the primosome assembly proteins, PriA, PriB, PriC, DnaT, DnaC, DnaB, and DnaG, are thought to help to restart DNA replication forks at recombinational intermediates. Redundant functions between priB and priC and synthetic lethality between priA2::kan and rep3 mutations raise the possibility that there may be multiple pathways for restarting replication forks in vivo. Herein, it is shown that priA2::kan causes synthetic lethality when placed in combination with either Δrep::kan or priC303:kan. These determinations were made using a nonselective P1 transduction-based viability assay. Two different priA2::kan suppressors (both dnaC alleles) were tested for their ability to rescue the priA-priC and priA-rep double mutant lethality. Only dnaC809,820 (and not dnaC809) could rescue the lethality in each case. Additionally, it was shown that the absence of the 3′-5′ helicase activity of both PriA and Rep is not the critical missing function that causes the synthetic lethality in the rep-priA double mutant. One model proposes that replication restart at recombinational intermediates occurs by both PriA-dependent and PriA-independent pathways. The PriA-dependent pathways require at least priA and priB or priC, and the PriA-independent pathway requires at least priC and rep. It is further hypothesized that the dnaC809 suppression of priA2::kan requires priC and rep, whereas dnaC809,820 suppression of priA2::kan does not.
Four Chromo-domain Proteins of Schizosaccharomyces pombe Differentially Repress Transcription at Various Chromosomal Locations
Authors: Thon Geneviève , Verhein-Hansen Janne 
Published: April 2021

Abstract
Transcription is repressed in regions of the fission yeast genome close to centromeres, telomeres, or the silent mating-type cassettes mat2-P and mat3-M. The repression involves the chromo-domain proteins Swi6 and Clr4. We report that two other chromo-domain proteins, Chp1 and Chp2, are also important for these position effects. Chp1 showed a specificity for centromeric regions. Its essentiality for the transcriptional repression of centromeric markers correlates with its importance for chromosome stability. Chp2 appeared more pleiotropic. Its effects on centromeric silencing were less pronounced than those of Chp1, and it participated in telomeric position effects and transcriptional silencing in the mating-type region. We also found that PolII-transcribed genes were repressed when placed in one of the Schizosaccharomyces pombe rDNA clusters, a situation analogous to that in the budding yeast Saccharomyces cerevisiae. Chp2, Swi6, Clr4, and, to a lesser extent, Chp1 participated in that repression.
Narrowing the Critical Regions for Mouse t Complex Transmission Ratio Distortion Factors by Use of Deletions
Authors: Lyon Mary F , Schimenti John C , Evans Edward P 
Published: April 2021

Abstract
Previously a deletion in mouse chromosome 17, T22H, was shown to behave like a t allele of the t complex distorter gene Tcd1, and this was attributed to deletion of this locus. Seven further deletions are studied here, with the aim of narrowing the critical region in which Tcd1 must lie. One deletion, T30H, together with three others, T31H, T33H, and T36H, which extended more proximally, caused male sterility when heterozygous with a complete t haplotype and also enhanced transmission ratio of the partial t haplotype t 6, and this was attributed to deletion of the Tcd1 locus. The deletions T29H, T32H, and T34H that extended less proximally than T30H permitted male fertility when opposite a complete t haplotype. These results enabled narrowing of the critical interval for Tcd1 to between the markers D17Mit164 and D17Leh48. In addition, T29H and T32H enhanced the transmission ratio of t6, but significantly less so than T30H. T34H had no effect on transmission ratio. These results could be explained by a new distorter located between the breakpoints of T29H and T34H (between T and D17Leh66E). It is suggested that the original distorter Tcd1 in fact consists of two loci: Tcd1a, lying between D17Mit164 and D17Leh48, and Tcd1b, lying between T and D17Leh66E.