bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genes Regulating the Remote Wing Margin Enhancer in the Drosophila cut Locus
Authors: Morcillo Patrick , Rosen Christina , Dorsett Dale 
Published: January 2021

Abstract
The mechanisms that allow enhancers to activate promoters from thousands of base pairs away are disrupted by the suppressor of Hairy-wing protein (SUHW) of Drosophila. SUHW binds a DNA sequence in the gypsy retrotransposon and prevents enhancers promoter-distal to a gypsy insertion in a gene from activating without affecting promoter-proximal enhancers. Several observations indicate that SUHW does not affect enhancer-binding activators. Instead, SUHW may interfere with factors that structurally facilitate interactions between an enhancer and promoter. To identify putative enhancer facilitators, a screen for mutations that reduce activity of the remote wing margin enhancer in the cut gene was performed. Mutations in scalloped, mastermind, and a previously unknown gene, Chip, were isolated. A TEA DNA-binding domain in the Scalloped protein binds the wing margin enhancer. Interactions between scalloped, mastermind and Chip mutations indicate that mastermind and Chip act synergistically with scalloped to regulate the wing margin enhancer. Chip is essential and also affects expression of a gypsy insertion in Ultrabithorax. Relative to mutations in scalloped or mastermind, a Chip mutation hypersensitizes the wing margin enhancer in cut to gypsy insertions. Therefore, Chip might encode a target of SUHW enhancer-blocking activity.
The Essence of Single Ascertainment
Authors: Hodge Susan E , Vieland Veronica J 
Published: January 2021

Abstract
We propose a fundamental new definition of single ascertainment, namely, that single ascertainment is any ascertainment scheme in whichP[pedigree is ascertained∣true structure of pedigree]∝p(θ)where p(θ) is some function of genetic parameters θ but is not a function of pedigree structure. Stated in words: Under single ascertainment, all pedigrees have equal (or proportional with respect to genetic parameters) probabilities of being ascertained, independent of pedigree size or structure. This new definition of single ascertainment allows us to show several results: (1 ) The correct likelihood consists of the probability of the data conditioned on the observed pedigree, divided by the function p(θ), whether sampling is “proband-independent” or “proband-dependent.” ( 2 ) More-familiar definitions of single ascertainment all represent special cases of our definition. ( 3 ) When p(θ) represents the prevalence of the trait being studied, our definition corresponds to “classical” single ascertainment, i.e., ascertainment through a single “proband.” However, the concept of p(θ) can also be generalized to represent the population frequency of configurations of affected relatives (such as affected sib pairs); we call this “generalized single ascertainment.”
Effective Sizes and Dynamics of Uniparentally and Diparentally Inherited Genes
Authors: Chesser Ronald K , Baker Robert J 
Published: January 2021

Abstract
Models to determine the temporal dynamics and spatial heterogeneity for maternally and paternally inherited genes were derived for populations that may or may not exhibit spatial subdivision. Results were compared to those for diparentally inherited genes. The models permit definition of parameters for mean and variance of litter sizes, breeding group (subpopulation) sizes, and numbers of female mates per male, dispersal rates, and multiple paternity. Exact solutions for asymptotic effective size and spatial divergence (F Ls) for maternal and paternal genes are derived. It is shown that solutions for effective size and F Ls are transformations of the same quadratic equation. When compared to values for diparentally inherited genes, it is shown that effective sizes for maternal genes may be considerably higher when female dispersal is low as in many mammalian taxa. Likewise, effective sizes for paternal genes may be higher than for diparentally inherited traits when male dispersal is relatively low, as in many species of birds. The traditional assumption that the effective size for maternal genes is approximately equal to the number of females is seldom realized. Spatial heterogeneity and temporal dynamics of genes are inextricably linked as is shown by the interdependency of effective size and spatial heterogeneity.
Measwring and Testing Genetic Differentiation With Ordered Versus Unordered Alleles
Authors: Pons O , Petit R J 
Published: January 2021

Abstract
Estimates and variances of diversity and differentiation measures in subdivided populations are proposed that can be applied to haplotypes (ordered alleles such as DNA sequences, which may contain a record of their own histories). Hence, two measures of differentiation can be compared for a single data set: one (GST) that makes use only of the allelic frequencies and the other (NST) for which similarities between the haplotypes are taken into account in addition. Tests are proposed to compare NST and GST with zero and with each other. The difference between NST and GST can be caused by several factors, including sampling artefacts, unequal effect of mutation rates and phylogeographic structure. The method presented is applied to a published data set where a nuclear DNA sequence had been determined from individuals of a grasshopper distributed in 24 regions of Europe. Additional insights into the genetic subdivision of these populations are obtained by progressively combining related haplotypes and reanalyzing the data each time.
The Mutation masculinizer (man) Defines a Sex-Determining Gene With Maternal and Zygotic Functions in Musca domestica L.
Authors: Schmidt R , Hediger M , Nöthiger R , Dübendorfer A 
Published: January 2021

In Musca domestica, the primary signal for sex determination is the dominant factor M, which is assumed to regulate a postulated female-determining gene F. Presence of M prevents expression of F so that male development ensues. In the absence of M, F can become active, which dictates the female pathway. The existence of F is inferred from FD, a dominant factor that is epistatic to M. We describe a new mutation masculinizer, which has all the properties expected for a null or strongly hypomorphic allele of F: (1) it maps to the same chromosomal location as FD, (2) homozygous man/man animals develop as males, (3) homozygous man/man clones generated in man/+ female larvae differentiate male structures, (4) man has a sex-determining maternal effect. About a third of the morphological males synthesize yolk proteins, which indicates that they are intersexual in internal structures. The maternal effect of man is complete in offspring that derive from homozygous man/man pole cells transplanted into female hosts. In this case, all man/+ progeny become fertile males that do not produce yolk proteins. A sex-determining maternal effect has previously been demonstrated for FD. Like F, maternal man + is needed for zygotic man + to become active, providing further evidence that man is a loss-of-function allele of F.
Highly Mismatched Molecules Resembling Recombination Intermediates Efficiently Transform Mismatch Repair Proficient Escherichia coli
Authors: Westmoreland James , Porter Gregory , Radman Miroslav , Resnick Michael A 
Published: January 2021

The ability of related DNAs to undergo recombination decreases with increased sequence divergence. Mismatch repair has been proposed to be a key factor in preventing homeologous recombination; however, the contribution of mismatch repair is not universal. Although mismatch repair has been proposed to act by preventing strand exchange and/or inactivating multiply mismatched heteroduplexes, there has been no systematic study to determine at what step(s) in recombination mismatch repair acts in vivo. Since heteroduplex is a commonly proposed intermediate in many models of recombination, we have investigated the consequences of mismatch repair on plasmids that are multiply mismatched in heteroduplex structures that are similar to those that might arise during recombination. Plasmids containing multiply mismatched regions were transformed into wild-type and Mut– Eschericia coli mutants. There was only a 30–40% reduction in transformation of Mut+ as compared to mutS and mutL strains for DNAs containing an 18% mismatched heteroduplex. The products obtained from mutS hosts differed from those obtained from Mut+ hosts in that there were many more colonies containing mixtures of two plasmids, due to survival of both strands of the heteroduplex. There were nearly 10 times more recombinants obtained from the mutS as compared to the wild-type host. Based on these results and those from other studies with E. coli and yeast, we propose that the prevention of recombination between highly diverged DNAs may be at a step earlier than heteroduplex formation.
A Recombinationally Repressed Region Between mat2 and mat3 Loci Shares Homology to Centromeric Repeats and Regulates Directionality of Mating-Type Switching in Fission Yeast
Authors: Grewal Shiv I S , Klar Amar J S 
Published: January 2021

Cells of the fission yeast Schizosaccharomyces pombe switch mating type by replacing genetic information at the transcriptionally active mat1 locus with sequences copied from one of two closely linked silent loci, mat2-P or mat3-M. By a process referred to as directionality of switching, cells predominantly switch to the opposite mat1 allele; the mat1-P allele preferentially recombines with mat3, while mat1-M selects the mat2. In contrast to efficient recombination at mat1, recombination within the adjoining mat2-mat3 interval is undetectable. We defined the role of sequences between mat2 and mat3, designated the K-region, in directionality as well as recombinational suppression. Cloning and sequencing analysis revealed that a part of the K-region is homologous to repeat sequences present at centromeres, which also display transcriptional and recombinational suppression. Replacement of 7.5 kb of the K-region with the ura4 + gene affected directionality in a variegated manner. Analysis of the swi6-mod locus, which was previously shown to affect directionality, in KΔ::ura4 + strains suggested the existence of at least two overlapping directionality mechanisms. Our work furthers the model that directionality is regulated by cell-type-specific organization of the heterochromatin-like structure in the mating-type region and provides evidence that the K-region contributes to silencing of the mat2-mat3 interval.
Phylogeographic Structure of White Oaks Throughout the European Continent
Authors: Dumolin-Lapègue S , Demesure B , Fineschi S , Le Come V , Petit R J 
Published: January 2021

Patterns of chloroplast DNA (cpDNA) variation were studied in eight white oak species by sampling 345 populations throughout Europe. The detection of polymorphisms by restriction analysis of PCR-amplified cpDNA fragments allowed the identification of 23 haplotypes that were phylogenetically ordered. A systematic hybridization and introgression between the eight species studied is evident. The levels of subdivision for unordered (G ST) and ordered (N ST) alleles are very high and close (0.83 and 0.85). A new statistical approach to the quantitative study of phylogeography is presented, which relies on the coefficients of differentiation G ST and N ST and the Mantel's test. Based on pairwise comparisons between populations, the significance of the difference between both coefficients is evaluated at a global and a local scale. The mapped distribution of the haplotypes indicates the probable routes of postglacial recolonization followed by oak populations that had persisted in southern refugia, especially in the Iberian peninsula, Italy and the Balkans. Most cpDNA polymorphisms appear to be anterior to the befinnina of the last recolonization. A subset of the preexisting haplotypes have merely expanded north, while others were left behind in the south.
The Prpl
+ Gene Required for Pre-mRNA Splicing in Schizosaccharomyces pombe Encodes a Protein That Contains TPR Motifs and Is Similar to Prp6p of Budding Yeast
Authors: Urushiyama Seiichi , Tani Tokio , Ohshima Yasumi 
Published: January 2021

Abstract
The prp (pre-mRNA processing) mutants of the fission yeast Schizosaccharomyces pombe have a defect in pre-mRNA splicing and accumulate mRNA precursors at a restrictive temperature. One of the prp mutants, prp1-4, also has a defect in poly(A)+ RNA transport. The prp1 + gene encodes a protein of 906 amino acid residues that contains 19 repeats of 34 amino acids termed tetratrico peptide repeat (TPR) motifs, which were proposed to mediate protein-protein interactions. The amino acid sequence of Prplp shares 29.6% identity and 50.6% similarity with that of the PRP6 protein of Saccharomyces cerevisiae, which is a component of the U4/U6 snRNP required for spliceosome assembly. No functional complementation was observed between S. pombe prp1 + and S. cerevisiae PRP6. We examined synthetic lethality of prp1-4 with the other known prp mutations in S. pombe. The results suggest that Prp1p interacts either physically or functionally with Prp4p, Prp6p and Prp13p. Interestingly, the prp1 + gene was found to be identical with the zer1 + gene that functions in cell cycle control. These results suggest that Prp1p/Zer1p is either directly or indirectly involved in cell cycle progression and/or poly(A)+ RNA nuclear export, in addition to pre-mRNA splicing.
Mu Element-Generated Gene Conversions in Maize Attenuate the Dominant Knotted Phenotype
Authors: Mathern Julie , Hake Sarah 
Published: January 2021

Abstract
The knotted1 gene was first defined by dominant mutations that affect leaf morphology. The original allele, Kn1-O, results from a 17-kb tandem duplication. Mutator (Mu) insertions near the junction of the two repeats suppress the leaf phenotype to different degrees depending on the position of the insertion. The Mu insertions also increase the frequency of recombination at Kn1-O to create derivative alleles in which the Mu element and one copy of the repeat are lost. These derivatives are normal in appearance. Here we describe two derivatives that retained the tandem duplication but gained insertions of 1.7 and 3 kb in length in place of the Mu element. In each case, the inserted DNA is a sequence that normally flanks the distal repeat unit. Thus, each derivative consists of a tandem duplication in which the repeat unit has been extended at its distal end by the length of the new insertion. The 1.7-kb insertion dampens the phenotype, as did the original Mu insertion, whereas the 3-kb insertion completely suppresses the knotted phenotype. We propose that gene conversion, stimulated by the double-strand break of the Mu excision, gave rise to these derivatives.
The Cak1p Protein Kinase Is Required at G1/S and G2/M in the Budding Yeast Cell Cycle
Authors: Sutton Ann , Freiman Richard 
Published: January 2021

Abstract
The CAK1 gene encodes the major CDK-activating kinase (CAK) in budding yeast and is required for activation of Cdc28p for cell cycle progression from G2 to M phase. Here we describe the isolation of a mutant allele of CAK1 in a synthetic lethal screen with the Sit4 protein phosphatase. Analysis of several different cak1 mutants shows that although the G2 to M transition appears most sensitive to loss of Cak1p function, Cak1p is also required for activation of Cdc28p for progression from G1 into S phase. Further characterization of these mutants suggests that, unlike the CAK identified from higher eukaryotes, Cak1p of budding yeast may not play a role in general transcription. Finally, although Cak1 protein levels and in vitro protein kinase activity do not fluctuate during the cell cycle, at least a fraction of Cak1p associates with higher molecular weight proteins, which may be important for its in vivo function.
Genetic Evidence That Recognition of cosQ the Signal for Termination of Phage λ DNA Packaging, Depends on the Extent of Head Filling
Authors: Cue David , Feiss Michael 
Published: January 2021

Abstract
Packaging a phage λ chromosome involves cutting the chromosome from a concatemer and translocating the DNA into a prohead. The cutting site, cos, consists of three subsites: cosN, the nicking site; cosB, a site required for packaging initiation; and cosQ a site required for termination of packaging. cosB contains three binding sites (R sequences) for gpNul, the small subunit of terminase. Because cosQ has sequence identity to the R sequences, it has been proposed that cosQ is also recognized by gpNul. Suppressors of cosB mutations were unable to suppress a cosQ point mutation. Suppressors of a cosQ mutation (cosQ1) were isolated and found to be of three sorts, the first affecting a base pair in cosQ. The second type of cosQ suppression involved increasing the length of the phage chromosome to a length near to the maximum capacity of the head shell. A third class of suppressors were missense mutations in gene B, which encodes the portal protein of the virion. It is speculated that increasing DNA length and altering the portal protein may reduce the rate of translocation, thereby increasing the efficiency of recognition of the mutant cosQ. None of the cosQ suppressors was able to suppress cosB mutations. Because cosQ and cosB mutations are suppressed by very different types of suppressors, it is concluded that cosQ and the R sequences of cosB are recognized by different DNA-binding determinants.
Annealing vs. Invasion in Phage λ Recombination
Authors: Stahl Mary M , Thomason Lynn , Poteete Anthony R , Tarkowski Trudee , Kuzminov Andrei , Stahl Franklin W 
Published: January 2021

Genetic recombination catalyzed by λ's Red pathway was studied in rec + and recA mutant bacteria by examining both intracellular λ DNA and mature progeny particles. Recombination of nonreplicating phage chromosomes was induced by double-strand breaks delivered at unique sites in vivo. In rec + cells, cutting only one chromosome gave nearly maximal stimulation of recombination; the recombinants formed contained relatively short hybrid regions, suggesting strand invasion. In contrast, in recA mutant cells, cutting the two parental chromosomes at non-allelic sites was required for maximal stimulation; the recombinants formed tended to be hybrid over the entire region between the two cuts, implying strand annealing. We conclude that, in the absence of RecA and the presence of non-allelic DNA ends, the Red pathway of λ catalyzes recombination primarily by annealing.
Exceptional Convergent Evolution in a Virus
Authors: Bull J J , Badgett M R , Wichman H A , Huelsenbeck J P , Hillis D M , Gulati A , Ho C , Molineux I J 
Published: January 2021

Abstract
Replicate lineages of the bacteriophage ϕX 174 adapted to growth at high temperature on either of two hosts exhibited high rates of identical, independent substitutions. Typically, a dozen or more substitutions accumulated in the 5.4-kilobase genome during propagation. Across the entire data set of nine lineages, 119 independent substitutions occurred at 68 nucleotide sites. Over half of these substitutions, accounting for one third of the sites, were identical with substitutions in other lineages. Some convergent substitutions were specific to the host used for phage propagation, but others occurred across both hosts. Continued adaptation of an evolved phage at high temperature, but on the other host, led to additional changes that included reversions of previous substitutions. Phylogenetic reconstruction using the complete genome sequence not only failed to recover the correct evolutionary history because of these convergent changes, but the true history was rejected as being a significantly inferior fit to the data. Replicate lineages subjected to similar environmental challenges showed similar rates of substitution and similar rates of fitness improvement across corresponding times of adaptation. Substitution rates and fitness improvements were higher during the initial period of adaptation than during a later period, except when the host was changed.
The Saccharomyces cerevisiae RAD30 Gene, a Homologue of Escherichia coli dinB and umuC, Is DNA Damage Inducible and Functions in a Novel Error-Free Postreplication Repair Mechanism
Authors: McDonald John P , Levine Arthur S , Woodgate Roger 
Published: January 2021

Abstract
Damage-inducible mutagenesis in prokaryotes is largely dependent upon the activity of the UmuD'C like proteins. Since many DNA repair processes are structurally and/or functionally conserved between prokaryotes and eukaryotes, we investigated the role of RAD30 a previously uncharacterized Saccharomyces cerevisiae DNA repair gene related to the Escherichia coli dinB, umuC and S. cerevisiae REV1 genes, in UV resistance and UV-induced mutagenesis. Similar to its prokaryotic homologues, RAD30 was found to be damage inducible. Like many S. cerevisiae genes involved in error-prone DNA repair, epistasis analysis clearly places RAD30 in the RAD6 group and rad30 mutants display moderate UV sensitivity reminiscent of rev mutants. However, unlike rev mutants, no defect in UV-induced reversion was seen in rad30 strains. While rad6 and rad18 are both epistatic to rad30, no epistasis was observed with rev1, rev3, rev7 or rad5, all of which are members of the RAD6 epistasis group. These findings suggest that RAD30 participates in a novel error-free repair pathway dependent on RAD6 and RADl8, but independent of REV1, REV3, REV7 and RAD5.
Allele-Specific Suppression by Formation of New Protein-Protein Interactions in Yeast
Authors: Sandrock Tanya M , O'Dell Johanna L , Adams Alison E M 
Published: January 2021

Abstract
Yeast fimbrin is encoded by the SAC6 gene, mutations of which suppress temperature-sensitive mutations in the actin gene (ACT1). To examine the mechanism of suppression, we have conducted a biochemical analysis of the interaction between various combinations of wild-type and mutant actin and Sac6 proteins. Previously, we showed that actin mutations that are suppressed by sac6 mutations encode proteins with a reduced affinity for wild-type Sac6p. In the present study, we have found that mutant Sac6 proteins bind more tightly to mutant actin than does wild-type SacGp, and thus compensate for weakened interactions caused by the mutant actin. Remarkably, we have also found that mutant Sac6 proteins bind more tightly to wild-type actin than does wild-type Sac6p. This result indicates that suppression does not occur through the restoration of the original contact site, but rather through the formation of a novel contact site. This finding argues against suppression occurring through a “lock-and-key” mechanism and suggests a mechanism involving more global increases in affinity between the two proteins. We propose that the most common kind of suppressors involving interacting proteins will likely occur through this less specific mechanism.