bluuebunny/crossref_metadata_2025 huggingface dataset:
The suppressor of Hairy-wing protein regulates the tissue-specific expression of the Drosophila gypsy retrotransposon.
Authors: Smith P A , Corces V G
Published: January 2021

The gypsy retrotransposon of Drosophila melanogaster causes mutations that show temporal and tissue-specific phenotypes. These mutant phenotypes can be reversed by mutations in su(Hw), a gene that also regulates the transcription of the gypsy element. Gypsy encodes a full-length 7.0-kb RNA that is expressed in the salivary gland precursors and fat body of the embryo, imaginal discs and fat body of larvae, and fat body and ovaries of adult females. The su(Hw)-binding region inserted upstream of the promoter of a lacZ reporter gene can induce beta-galactosidase expression in a subset of the embryonic and larval tissues where gypsy is normally transcribed. This expression is dependent on the presence of a functional su(Hw) product, suggesting that this protein is a positive activator of gypsy transcription. Flies transformed with a construct in which the 5' LTR and leader sequences of gypsy are fused to lacZ show beta-galactosidase expression in all tissues where gypsy is normally expressed, indicating that sequences other than the su(Hw)-binding site are required for proper spatial and temporal expression of gypsy. Mutations in the zinc fingers of su(Hw) affect its ability to bind DNA and to induce transcription of the lacZ reporter gene. Two other structural domains of su(Hw) also play an important role in transcriptional regulation of gypsy. Deletion of the amino-terminal acidic domain results in the loss of lacZ expression in larval fat body and adult ovaries, whereas mutations in the leucine zipper region result in an increase of lacZ expression in larval fat body and a decrease in adult ovaries. These effects might be the result of interactions of su(Hw) with activator and repressor proteins through the acidic and leucine zipper domains to produce the final pattern of tissue-specific expression of gypsy.
Genetic population structure and gene flow in the Atlantic cod Gadus morhua: a comparison of allozyme and nuclear RFLP loci.
Authors: Pogson G H , Mesa K A , Boutilier R G
Published: January 2021

High levels of gene flow have been implicated in producing uniform patterns of allozyme variation among populations of many marine fish species. We have examined whether gene flow is responsible for the limited population structure in the Atlantic cod, Gadus morhua L., by comparing the previously published patterns of variation at 10 allozyme loci to 17 nuclear restriction fragment length polymorphism (RFLP) loci scored by 11 anonymous cDNA clones. Unlike the allozyme loci, highly significant differences were observed among all populations at the DNA markers in a pattern consistent with an isolation-by-distance model of population structure. The magnitude of allele frequency variation at the nuclear RFLP loci significantly exceeded that observed at the protein loci (chi 2 = 24.6, d.f. = 5, P < 0.001). Estimates of gene flow from the private alleles method were similar for the allozymes and nuclear RFLPs. From the infinite island model, however, estimates of gene flow from the DNA markers were fivefold lower than indicated by the proteins. The discrepancy between gene flow estimates, combined with the observation of a large excess of rare RFLP alleles, suggests that the Atlantic cod has undergone a recent expansion in population size and that populations are significantly displaced from equilibrium. Because gene flow is a process that affects all loci equally, the heterogeneity observed among populations at the DNA level eliminates gene flow as the explanation for the homogeneous allozyme patterns. Our results suggest that a recent origin of cod populations has acted to constrain the extent of population differentiation observed at weakly polymorphic loci and implicate a role for selection in affecting the distribution of protein variation among natural populations in this species.
Identification of hepatocarcinogen-resistance genes in DBA/2 mice.
Authors: Lee G H , Bennett L M , Carabeo R A , Drinkwater N R
Published: January 2021

Male DBA/2J mice are approximately 20-fold more susceptible than male C57BL/6J mice to hepatocarcinogenesis induced by perinatal treatment with N,N-diethylnitrosamine (DEN). In order to elucidate the genetic control of hepatocarcinogenesis in DBA/2J mice, male BXD recombinant inbred, D2B6F1 x B6 backcross, and D2B6F2 intercross mice were treated at 12 days of age with DEN and liver tumors were enumerated at 32 weeks. Interestingly, the distribution of mean tumor multiplicities among BXD recombinant inbred strains indicated that hepatocarcinogen-sensitive DBA/2 mice carry multiple genes with opposing effects on the susceptibility to liver tumor induction. By analyzing D2B6F1 x B6 backcross and D2B6F2 intercross mice for their liver tumor multiplicity phenotypes and for their genotypes at simple sequence repeat marker loci, we mapped two resistance genes carried by DBA/2J mice, designated Hcr1 and -2, to chromosomes 4 and 10, respectively. Hcr1 and Hcr2 resolved the genetic variance in the backcross population well, indicating that these resistance loci are the major determinants of the variance in the backcross population. Although our collection of 100 simple sequence repeat markers allowed linkage analysis for approximately 95% of the genome, we failed to map any sensitivity alleles for DBA/2J mice. Thus, it is likely that the susceptibility of DBA/2J mice is the consequence of the combined effects of multiple sensitivity loci.
Modeling interference in genetic recombination.
Authors: McPeek M S , Speed T P
Published: January 2021

In analyzing genetic linkage data it is common to assume that the locations of crossovers along a chromosome follow a Poisson process, whereas it has long been known that this assumption does not fit the data. In many organisms it appears that the presence of a crossover inhibits the formation of another nearby, a phenomenon known as "interference." We discuss several point process models for recombination that incorporate position interference but assume no chromatid interference. Using stochastic simulation, we are able to fit the models to a multilocus Drosophila dataset by the method of maximum likelihood. We find that some biologically inspired point process models incorporating one or two additional parameters provide a dramatically better fit to the data than the usual "no-interference" Poisson model.
Statistical analysis of chromatid interference.
Authors: Zhao H , McPeek M S , Speed T P
Published: January 2021

The nonrandom occurrence of crossovers along a single strand during meiosis can be caused by either chromatid interference, crossover interference or both. Although crossover interference has been consistently observed in almost all organisms since the time of the first linkage studies, chromatid interference has not been as thoroughly discussed in the literature, and the evidence provided for it is inconsistent. In this paper with virtually no restrictions on the nature of crossover interference, we describe the constraints that follow from the assumption of no chromatid interference for single spore data. These constraints are necessary consequences of the assumption of no chromatid interference, but their satisfaction is not sufficient to guarantee no chromatid interference. Models can be constructed in which chromatid interference clearly exists but is not detectable with single spore data. We then extend our analysis to cover tetrad data, which permits more powerful tests of no chromatid interference. We note that the traditional test of no chromatid interference based on tetrad data does not make full use of the information provided by the data, and we offer a statistical procedure for testing the no chromatid interference constraints that does make full use of the data. The procedure is then applied to data from several organisms. Although no strong evidence of chromatid interference is found, we do observe an excess of two-strand double recombinations, i.e., negative chromatid interference.
Control of cleavage spindle orientation in Caenorhabditis elegans: the role of the genes par-2 and par-3.
Authors: Cheng N N , Kirby C M , Kemphues K J
Published: January 2021

Polarized asymmetric divisions play important roles in the development of plants and animals. The first two embryonic cleavages of Caenorhabditis elegans provide an opportunity to study the mechanisms controlling polarized asymmetric divisions. The first cleavage is unequal, producing daughters with different sizes and fates. The daughter blastomeres divide with different orientations at the second cleavage; the anterior blastomere divides equally across the long axis of the egg, whereas the posterior blastomere divides unequally along the long axis. We report here the results of our analysis of the genes par-2 and par-3 with respect to their contribution to the polarity of these divisions. Strong loss-of-function mutations in both genes lead to an equal first cleavage and an altered second cleavage. Interestingly, the mutations exhibit striking gene-specific differences at the second cleavage. The par-2 mutations lead to transverse spindle orientations in both blastomeres, whereas par-3 mutations lead to longitudinal spindle orientations in both blastomeres. The spindle orientation defects correlate with defects in centrosome movements during both the first and the second cell cycle. Temperature shift experiments with par-2(it5ts) indicate that the par-2(+) activity is not required after the two-cell stage. Analysis of double mutants shows that par-3 is epistatic to par-2. We propose a model wherein par-2(+) and par-3(+) act in concert during the first cell cycle to affect asymmetric modification of the cytoskeleton. This polar modification leads to different behaviors of centrosomes in the anterior and posterior and leads ultimately to blastomere-specific spindle orientations at the second cleavage.
Analysis of the multiple roles of gld-1 in germline development: interactions with the sex determination cascade and the glp-1 signaling pathway.
Authors: Francis R , Maine E , Schedl T
Published: January 2021

The Caenorhabditis elegans gene gld-1 is essential for oocyte development; in gld-1 (null) hermaphrodites, a tumor forms where oogenesis would normally occur. We use genetic epistasis analysis to demonstrate that tumor formation is dependent on the sexual fate of the germline. When the germline sex determination pathway is set in the female mode (terminal fem/fog genes inactive), gld-1 (null) germ cells exit meiotic prophase and proliferate to form a tumor, but when the pathway is set in the male mode, they develop into sperm. We conclude that the gld-1 (null) phenotype is cell-type specific and that gld-1(+) acts at the end of the cascade to direct oogenesis. We also use cell ablation and epistasis analysis to examine the dependence of tumor formation on the glp-1 signaling pathway. Although glp-1 activity promotes tumor growth, it is not essential for tumor formation by gld-1 (null) germ cells. These data also reveal that gld-1(+) plays a nonessential (and sex nonspecific) role in regulating germ cell proliferation before their entry into meiosis. Thus gld-1(+) may negatively regulate proliferation at two distinct points in germ cell development: before entry into meiotic prophase in both sexes (nonessential premeiotic gld-1 function) and during meiotic prophase when the sex determination pathway is set in the female mode (essential meiotic gld-1 function).
Structure and evolution of genes encoding polyubiquitin and ubiquitin-like proteins in Arabidopsis thaliana ecotype Columbia.
Authors: Callis J , Carpenter T , Sun C W , Vierstra R D
Published: January 2021

The Arabidopsis thaliana ecotype Columbia ubiquitin gene family consists of 14 members that can be divided into three types of ubiquitin genes; polyubiquitin genes, ubiquitin-like genes and ubiquitin extension genes. The isolation and characterization of eight ubiquitin sequences, consisting of four polyubiquitin genes and four ubiquitin-like genes, are described here, and their relationships to each other and to previously identified Arabidopsis ubiquitin genes were analyzed. The polyubiquitin genes, UBQ3, UBQ10, UBQ11 and UBQ14, contain tandem repeats of the 228-bp ubiquitin coding region. Together with a previously described polyubiquitin gene, UBQ4, they differ in synonymous substitutions, number of ubiquitin coding regions, number and nature of nonubiquitin C-terminal amino acid(s) and chromosomal location, dividing into two subtypes; the UBQ3/UBQ4 and UBQ10/UBQ11/UBQ14 subtypes. Ubiquitin-like genes, UBQ7, UBQ8, UBQ9 and UBQ12, also contain tandem repeats of the ubiquitin coding region, but at least one repeat per gene encodes a protein with amino acid substitutions. Nucleotide comparisons, Ks value determinations and neighbor-joining analyses were employed to determine intra- and intergenic relationships. In general, the rate of synonymous substitution is too high to discern related repeats. Specific exceptions provide insight into gene relationships. The observed nucleotide relationships are consistent with previously described models involving gene duplications followed by both unequal crossing-over and gene conversion events.
On the clustered exchanges of the RecBCD pathway operating on phage lambda.
Authors: Stahl F W , Shurvinton C E , Thomason L C , Hill S , Stahl M M
Published: January 2021

Lytic cycle crosses of Red- Gam- phage lambda were conducted in rec+ Escherichia coli carrying one or another plasmid with homology to lambda. Lambda x lambda recombinants and lambda x plasmid recombinants were formed by RecBCD-mediated recombination. We showed previously that the act of recombining with a plasmid alters the disposition of selected lambda x lambda exchanges. This work reports that the relationships between the lambda x plasmid and the lambda x lambda exchanges is unaltered by the removal from one lambda parent of the homology shared with the plasmid. This result supports our view that a reciprocal exchange, allowing for cointegrate formation, is associated with but mechanistically separable from a (presumably) nonreciprocal lambda x lambda exchange. The nature of this relationship is independent of lambda's Rap function, which is shown to alter the ratio of cointegrate formation (splices) to marker pick-up (patches) in lambda x plasmid recombination mediated by the RecBCD pathway.
Multiple elements and auto-repression regulate Rox1, a repressor of hypoxic genes in Saccharomyces cerevisiae.
Authors: Deckert J , Perini R , Balasubramanian B , Zitomer R S
Published: January 2021

The ROX1 gene encodes a heme-induced repressor of hypoxic genes in yeast. Using RNA blot analysis and a ROX1/lacZ fusion construct that included the ROX1 upstream region and only the first codon, we discovered that Rox1 represses its own expression. Gel-retardation experiments indicated that Rox1 was capable of binding to its own upstream region. Overexpression of Rox1 from the inducible GAL1 promoter was found to be inhibitory to cell growth. Also, we found that, as reported previously, Hap1 is partially responsible for heme-induction of ROX1, but, in addition, it also may play a role in ROX1 repression in the absence of heme. There is a second repressor of anaerobic ROX1 expression that requires the general repressor Tup1/Ssn6 for its function.
High resolution mapping of genetic factors affecting abdominal bristle number in Drosophila melanogaster.
Authors: Long A D , Mullaney S L , Reid L A , Fry J D , Langley C H , Mackay T F
Published: January 2021

Factors responsible for selection response for abdominal bristle number and correlated responses in sternopleural bristle number were mapped to the X and third chromosome of Drosophila melanogaster. Lines divergent for high and low abdominal bristle number were created by 25 generations of artificial selection from a large base population, with an intensity of 25 individuals of each sex selected from 100 individuals of each sex scored per generation. Isogenic chromosome substitution lines in which the high (H) X or third chromosome were placed in an isogenic low (L) background were derived from the selection lines and from the 93 recombinant isogenic (RI) HL X and 67 RI chromosome 3 lines constructed from them. Highly polymorphic neutral roo transposable elements were hybridized in situ to the polytene chromosomes of the RI lines to create a set of cytogenetic markers. These techniques yielded a dense map with an average spacing of 4 cM between informative markers. Factors affecting bristle number, and relative viability of the chromosome 3 RI lines, were mapped using a multiple regression interval mapping approach, conditioning on all markers > or = 10 cM from the tested interval. Two factors with large effects on abdominal bristle number were mapped on the X chromosome and five factors on the third chromosome. One factor with a large effect on sternopleural bristle number was mapped to the X and two were mapped to the third chromosome; all factors with sternopleural effects corresponded to those with effects on abdominal bristle number. Two of the chromosome 3 factors with large effects on abdominal bristle number were also associated with reduced viability. Significant sex-specific effects and epistatic interactions between mapped factors of the same order of magnitude as the additive effects were observed. All factors mapped to the approximate positions of likely candidate loci (ASC, bb, emc, h, mab, Dl and E(spl), previously characterized by mutations with large effects on bristle number.
Protected P-element termini suggest a role for inverted-repeat-binding protein in transposase-induced gap repair in Drosophila melanogaster.
Authors: Staveley B E , Heslip T R , Hodgetts R B , Bell J B
Published: January 2021

P-element transposition is thought to occur by a cut-and paste mechanism that generates a double-strand break at the donor site, the repair of which can lead to internally deleted elements. We have generated a series of both phenotypically stronger and weaker allelic derivatives of vg21, a vestigial mutant caused by a P-element insertion in the 5' region of the gene. Virtually all of the new alleles arose by internal deletion of the parental element in vg21, and we have characterized a number of these internally deleted P elements. Depending upon the selection scheme used, we see a very different spectrum of amount and source of P-element sequences in the resultant derivatives. Strikingly, most of the breakpoints occur within the inverted-repeats such that the last 15-17 bp of the termini are retained. This sequence is known to bind the inverted-repeat-binding protein (IRBP). We propose that the IRBP may act to preserve the P-element ends when transposition produces a double-strand gap. This allows the terminus to serve as a template upon which DNA synthesis can act to repair the gap. Filler sequences found at the breakpoints of the internally deleted P elements resemble short stretches, often in tandem arrays, of these terminal sequences. The structure of the filler sequences suggests replication slippage may occur during the process of gap repair.
Interaction of Mre11 and Rad50: two proteins required for DNA repair and meiosis-specific double-strand break formation in Saccharomyces cerevisiae.
Authors: Johzuka K , Ogawa H
Published: January 2021

A temperature-sensitive mre11-1 mutation of Saccharomyces cerevisiae causes defects in meiotic recombination and DNA repair during vegetative growth at a restrictive temperature. We cloned the MRE11 gene and found that it encodes a 643-amino acid protein with a highly acidic region containing a heptad repeat of Asp at its C-terminus and is located downstream of YMR44 near the RNA1 locus on the right arm of chromosome XIII. Transcripts of the MRE11 gene increased transiently and showed the same kinetics as that of the RAD50 gene during meiosis. In a mre11 disruption mutant (mre11::hisG), meiosis-specific double-strand break (DSB) formation is abolished. A comparison of the properties of mre11::hisG and a rad50 deletion mutant (rad50 delta) indicated that both mutants exhibited similar phenotypes in both meiosis and mitosis. Characterization of two double mutants, mre11::hisG rad50 delta and mre11::hisG rad50S, showed that MRE11 and RAD50 belong to the same epistasis group with respect to meiotic DSB formation and mitotic DNA repair. Using a two-hybrid system, we found that Mre11 interacts with Rad50 and itself in vivo. These results suggest that Mre11 and Rad50 proteins work in a complex in DSB formation and DNA repair during vegetative growth.
Structure and regulation of a complex locus: the cut gene of Drosophila.
Authors: Jack J , DeLotto Y
Published: January 2021

The cut locus encodes a homeobox protein that is localized in the nuclei of a variety of tissues and is required for proper morphogenesis of those tissues. Cut protein is required in embryonic and adult external sensory organs, where its absence results in conversion of the organs to chordotonal organs. Expression of cut also occurs in the Malpighian tubules, spiracles, central nervous system, and a number of other tissues. Gypsy transposon insertions upstream of the cut promoter block expression in subsets of these tissues. The effect of the gypsy insertions is polar, with those farthest from the promoter affecting the fewest tissues. The hypothesis that gypsy insertions block a series of tissue-specific enhancer elements that are distributed over a region of 80 kb upstream of the promoter predicts the location of the enhancers for cut expression in each of the tissues in which it is active in embryos. DNA fragments from this region drive expression of a reporter gene in each of the embryonic tissues in which endogenous cut gene is expressed. Each tissue has its own enhancer, and none of the enhancers require the activity of the endogenous cut gene to function.
Genetic characterization of the Mutator system in maize: behavior and regulation of Mu transposons in a minimal line.
Authors: Lisch D , Chomet P , Freeling M
Published: January 2021

Most Mutator lines of maize harbor several different classes of Mu transposons, each of which may be present in high copy number. The regulatory element is also often found in high copy number, and it is this element's behavior that is presumed to cause the non-Mendelian inheritance of Mutator activity. Using a very simple Mutator line, we demonstrate tha MuDR-1, a regulator of the Mutator system, can functionally replace standard non-Mendelian Mutator activity and that MuDR-1 is associated with the loss of methylation of the termini of another Mu transposon. Further, we show that Mu transposons can transpose duplicatively, that reinsertion tends to be into unlinked sites, and that MuDR-1 frequently suffers deletions. Changes in chromosomal position and the mode of sexual transmission are shown to be associated with changes in the frequency of MuDR-1 duplication and with the activity of MuDR-1 as monitored by the excision frequency of a reporter transposon of the Mu family, Mu1. Our data are derived from a Minimal Mutator Line in which there are relatively few Mu transposons, including one MuDR-1 regulator and as few as one Mu1 reporter. The seemingly enigmatic results that have been obtained using more complicated Mu genotypes are reinterpreted using simple Mendelian principles. We have borrowed a gap-repair model from Drosophila biologists to explain both duplications and deletions of MuDR-1.
Identification of genes required for alpha 2 repression in Saccharomyces cerevisiae.
Authors: Wahi M , Johnson A D
Published: January 2021

Transcriptional repression of the a-specific genes in Saccharomyces cerevisiae alpha cells involves the concerted action of several proteins. The homeodomian protein alpha 2, together with MCM1, recruits two general transcriptional repressors, SSN6 and TUP1, to the promoters of a-specific genes. SSN6 and TUP1 then mediate repression of the a-specific genes. SIN4, another general negative regulator, is required for this repression, but unlike tup1 or ssn6 deletions, sin4 deletions cause only partial loss of repression. We have screened for other genes required for a-specific gene repression in alpha cells. In addition to recovering multiple alleles of previously identified genes required for this process (referred to as alpha 2 repression), we have identified four other genes, designated ARE1, ARE2, ARE3, and ARE4 (for alpha 2 repression). Recessive mutations in the ARE genes cause partial loss of a-specific gene repression and cause pleiotropic phenotypes similar to those resulting from mutations in SSN6, TUP1, or SIN4, suggesting that the ARE genes are general negative regulators. Based on our initial analysis, we propose that two distinct classes of general negative regulators cooperate to bring about full levels of alpha 2 repression. The sequence of ARE1 revealed that it encodes a CDC28-related protein kinase, identical to UME5, and thus suggests that protein phosphorylation plays a role in alpha 2 repression.
Role of Erf recombinase in P22-mediated plasmid transduction.
Authors: Garzón A , Cano D A , Casadesús J
Published: January 2021

In the absence of host RecA function, plasmid transduction by bacteriophage P22 can be mediated by Erf recombinase. Erf is not carried on the infecting particle but synthesized upon infection. In the recipient cell, Erf can promote both generalized plasmid transduction (which requires the circularization of plasmids transduced as linear multimers) and specialized plasmid transduction (which requires the release of plasmid DNA from linear plasmid-phage cointegrates). Both processes of Erf-mediated plasmid transduction require host RecBCD function. In contrast, RecBCD is not required for Erf-mediated circularization of P22 DNA.
Developmental genetical analysis and molecular cloning of the abnormal oocyte gene of Drosophila melanogaster.
Authors: Tomkiel J , Fanti L , Berloco M , Spinelli L , Tamkun J W , Wakimoto B T , Pimpinelli S
Published: January 2021

Studies of the abnormal oocyte (abo) gene of Drosophila melanogaster have previously been limited to the analysis of a single mutant allele, abnormal oocyte1 (abo1). The abo1 mutation causes a maternal-effect lethality that can be partially rescued zygotically by the abo+ allele and by increasing the dosage of specific regions of heterochromatin denoted ABO. This report describes the properties of abo2, a new P-element-induced allele that allowed us to reexamine the nature of maternal-effect defect. Comparisons of the phenotype of progeny of abo1/abo1 and abo1/abo2 females show that the preblastoderm lethality previously described as a component of the abo mutant maternal effect results from a recessive fertilization defect associated with the abo1 chromosome. We demonstrate here that the abo-induced maternal effect lethality occurs predominately late in embryogenesis after cuticle deposition but before hatching. The phenocritical period for zygotic rescue by heterochromatin coincides with this period of late embryogenesis. We have used the abo2 mutation to map and molecularly clone the gene. We show that the abo gene is located in the 32C cytogenetic interval and identify the putative abo transcript from mRNA isolated from adult females. Using germline transformation, we show that a 9-kb genomic fragment to which the transcript maps, partially fulfills requirement for maternal and zygotic abo+ function.
Separating population structure from population history: a cladistic analysis of the geographical distribution of mitochondrial DNA haplotypes in the tiger salamander, Ambystoma tigrinum.
Authors: Templeton A R , Routman E , Phillips C A
Published: January 2021

Nonrandom associations of alleles or haplotypes with geographical location can arise from restricted gene flow, historical events (fragmentation, range expansion, colonization), or any mixture of these factors. In this paper, we show how a nested cladistic analysis of geographical distances can be used to test the null hypothesis of no geographical association of haplotypes, test the hypothesis that significant associations are due to restricted gene flow, and identify patterns of significant association that are due to historical events. In this last case, criteria are given to discriminate among contiguous range expansion, long-distance colonization, and population fragmentation. The ability to make these discriminations depends critically upon an adequate geographical sampling design. These points are illustrated with a worked example: mitochondrial DNA haplotypes in the salamander Ambystoma tigrinum. For this example, prior information exists about restricted gene flow and likely historical events, and the nested cladistic analyses were completely concordant with this prior information. This concordance establishes the plausibility of this nested cladistic approach, but much future work will be necessary to demonstrate robustness and to explore the power and accuracy of this procedure.
Nucleotide polymorphism in the 5' promoter region of esterase 6 in Drosophila melanogaster and its relationship to enzyme activity variation.
Authors: Odgers W A , Healy M J , Oakeshott J G
Published: January 2021

A 974-bp region immediately 5' of the esterase 6 gene was sequenced in 17 field derived third chromosome isoallelic lines. Twenty-three polymorphisms were identified, only two in the first 400 bp 5' but 16 in a 325-bp region from -494 to -819 bp. This distribution differs from previously published patterns in Drosophila simulans and D. mauritiana, where the first 800 bp are highly conserved. Fourteen common polymorphisms in the 325-bp region above are all in strong linkage disequilibrium with each other. Moreover, most of the haplotypes defined by the total of 23 polymorphisms fall into two groups that differ as a block at all 14 of these latter sites. Sequence differences between the two groups include some restriction sites that were scored in an earlier study of RFLPs and EST6 enzyme phenotypes among 42 isoallelic lines from the same population. By collating the two studies, we show that one haplotype group yields approximately 15% lower EST6 enzyme activity in adult males than the other. The promoter haplotypes show only weak disequilibrium with the esterase 6 fast/slow allozyme polymorphism, so it seems unlikely that previously reported latitudinal clines in the allozyme frequencies are due to their hitchhiking along with selection on the promoter difference.
Phenotypic and molecular analysis of a transgenic insertional allele of the mouse Fused locus.
Authors: Perry W L , Vasicek T J , Lee J J , Rossi J M , Zeng L , Zhang T , Tilghman S M , Costantini F
Published: January 2021

Spontaneous mutations at the mouse Fused (Fu) locus cause dominant skeletal and neurological defects and recessive lethal embryonic defects including neuroectodermal abnormalities and axial duplications. Here, we describe a new allele at the Fu locus caused by a transgenic insertional mutation, H epsilon 46. Embryos homozygous for the H epsilon 46 insertion die at day 9-10 post coitum and display phenotypic defects similar to those associated with Fu alleles. The H epsilon 46 locus was cloned and shown to contain a 20-kb deletion at the site of transgene insertion with no other detectable rearrangements. Genomic probes from the H epsilon 46 locus were mapped to a genetic locus closely linked to Fu on chromosome 17 and were hybridized to a YAC contig covering the FuKi critical region. Compound heterozygotes between H epsilon 46 and FuKi were inviable and displayed abnormalities at the same stage of embryogenesis as do homozygotes for either of the two mutations, demonstrating that these two recessive lethal mutations belong to the same complementation group. A genomic probe from the wild-type H epsilon 46 locus detected a transcript that is disrupted by the transgenic insertion, representing a candidate for the wild-type allele of Fused.
teosinte branched1 and the origin of maize: evidence for epistasis and the evolution of dominance.
Authors: Doebley J , Stec A , Gustus C
Published: January 2021

Two quantitative trait loci (QTL) controlling differences in plant and inflorescence architecture between maize and its progenitor (teosinte) were analyzed. Complementation tests indicate that one of these, which is on chromosome arm 1L, is the locus for the maize mutant teosinte branched1 (tb1). This QTL has effects on inflorescence sex and the number and length of internodes in the lateral branches and inflorescences. This QTL has strong phenotypic effects in teosinte background but reduced effects in maize background. The second QTL, which is on chromosome arm 3L, affects the same traits as the QTL on 1L. We identify two candidate loci for this QTL. The effects of this QTL on several traits are reduced in both maize and teosinte background as compared to a maize-teosinte F2 population. Genetic background appears to affect gene action for both QTL. Analysis of a population in which both QTL were segregating revealed that they interact epistatically. Together, these two QTL substantially transform both plant and inflorescence architecture. We propose that tb1 is involved in the plant's response to local environment to produce either long or short branches and that maize evolution involved a change at this locus to produce short branches under all environments.
Organization of paramutagenicity in R-stippled maize.
Authors: Kermicle J L , Eggleston W B , Alleman M
Published: January 2021

In heterozygotes, R-stippled (R-st) reduces the pigmenting potential of sensitive r alleles heritably (paramutation). R-st is comprised of four r genes arranged in direct orientation. Unequal crossing over within R-st generates deletion products retaining from one to three r genes. Paramutagenic strength decreased in parallel with copy number, both among internal and distal deletions. Single-gene R-st derivatives were nonparamutagenic. This was so whether or not the single gene retained the transposable element (I-R) responsible for seed spotting. Adding back r genes by intragenic recombination increased paramutagenicity in proportion to total gene number. Each member of a set of overlapping deletions retained moderately strong activity, showing that no single r gene or intragenic region is required for paramutagenicity. Proximal and distal loss R-st derivatives, each retaining two r genes, were less paramutagenic in trans than the corresponding four copy cis combination, indicating R-st's paramutagenic determinants function as a cis-interdependent unit in bringing about modification of a sensitive allele.
Properties of statistical tests of neutrality for DNA polymorphism data.
Authors: Simonsen K L , Churchill G A , Aquadro C F
Published: January 2021

A class of statistical tests based on molecular polymorphism data is studied to determine size and power properties. The class includes Tajima's D statistic as well as the D* and F* tests proposed by Fu and Li. A new method of constructing critical values for these tests is described. Simulations indicate that Tajima's test is generally most powerful against the alternative hypotheses of selective sweep, population bottleneck, and population subdivision, among tests within this class. However, even Tajima's test can detect a selective sweep or bottleneck only if it has occurred within a specific interval of time in the recent past or population subdivision only when it has persisted for a very long time. For greatest power against the particular alternatives studied here, it is better to sequence more alleles than more sites.
Genetic mapping and non-Mendelian segregation of mating type loci in the oomycete, Phytophthora infestans.
Authors: Judelson H S , Spielman L J , Shattock R C
Published: January 2021

DNA markers linked to the determinants of mating type in the oomycete, Phytophthora infestans, were identified and used to address the genetic basis of heterothallism in the normally diploid fungus. Thirteen loci linked to the A1 and A2 mating types were initially identified by bulked segregant analysis using random amplified polymorphic DNA markers (RAPDs) and subsequently scored in three crosses polymorphisms (SSCP), cleaved amplified polymorphisms (CAPS), or allele-specific polymerase chain reaction markers (AS-PCR). All DNA markers mapped to a single region, consistent with a single locus determining both mating types. Long-range restriction mapping also demonstrated the linkage of the markers to one region and delimited the mating type locus to a 100-kb region. The interval containing the mating type locus displayed non-Mendelian segregation as only two of the four expected genotypes were detected in progeny. This is consistent with a system of balance lethal loci near the mating type locus. A model for mating type determination is presented in which the balanced lethals exclude form progeny those with potentially conflicting combinations of mating type alleles, such as those simultaneously expressing A1 and A2 functions.
A role for the KP leucine zipper in regulating P element transposition in Drosophila melanogaster.
Authors: Andrews J D , Gloor G B
Published: January 2021

The KP element can repress P element mobility in Drosophila melanogaster. Three mutant KP elements were made that had either two amino acid substitutions or a single amino acid deletion in the putative leucine zipper domain found in the KP polypeptide. Each KP element was expressed from the actin 5C proximal promoter. The wild-type control construct strongly repressed P element mobility, measured by the GD sterility and sn(w) mutability assays, in a position-independent manner. The single amino acid deletion mutant failed to repress P mobility by the double amino acid substitution mutants was position dependent. The results show that the leucine zipper of the KP polypeptide is important for P element regulation. This supports the multimer-poisoning model of P element repression, because leucine zipper motifs are involved in protein-protein interactions.
Genetic interactions between the Drosophila Abelson (Abl) tyrosine kinase and failed axon connections (fax), a novel protein in axon bundles.
Authors: Hill K K , Bedian V , Juang J L , Hoffmann F M
Published: January 2021

Mutations in the failed axon connections (fax) gene have been identified as dominant genetic enhancers of the Abl mutant phenotype. These mutations in fax all result in defective or absent protein product. In a genetic background with wild-type Abl function, the fax loss-of-function alleles are homozygous viable, demonstrating that fax is not an essential gene unless the animal is also mutant for Abl. The fax gene encodes a novel 47-kD protein expressed in a developmental pattern similar to that of Abl in the embryonic mesoderm and axons of the central nervous system. The conditional, extragenic noncomplementation between fax and another Abl modifier gene, disabled, reveal that the two proteins are likely to function together in a process downstream or parallel to the Abl protein tyrosine kinase.
Allelic interactions heritably alter the activity of a metastable maize pl allele.
Authors: Hollick J B , Patterson G I , Coe E H , Cone K C , Chandler V L
Published: January 2021

The maize pl locus encodes a transcriptional activator of anthocyanin biosynthetic genes. The Pl-Rhoades (Pl-Rh) allele confers robust purple anthocyanin pigment in several tissues. Spontaneous derivatives of Pl-Rh, termed Pl'-mahogany (Pl'-mah), arise that confer reduced pigment and are meiotically heritable. These derivatives influence other Pl-Rh alleles such that only Pl'-mah alleles are transmitted form a Pl-Rh/Pl'mah heterozygote. Genetic crosses establish that chromosomal segregation distortion does not explain this exclusive transmission and suggest that Pl-Rh invariably changes to Pl'-mah when exposed to Pl'-mah. Such behavior is a hallmark of paramutation. Cosegregation experiments demonstrate that this paramutagenic activity is genetically linked to the pl locus. By visually quantifying pl action through successive crosses, we find that phenotypic expression is inversely related to paramutation at two other maize loci, b and r. Previous analysis of b and r paramutation revealed extensive differences and led to suggestions of distinct molecular mechanisms. Consideration of the common features of all three systems reinvigorates the interpretation that the mechanistic processes of these three allelic interactions are similar.
Mutant rec-1 eliminates the meiotic pattern of crossing over in Caenorhabditis elegans.
Authors: Zetka M C , Rose A M
Published: January 2021

Meiotic crossovers are not randomly distributed along the chromosome. In Caenorhabditis elegans the central portions of the autosomes have relatively few crossovers compared to the flanking regions. We have measured the frequency of crossing over for several intervals across chromosome I in strains mutant for rec-1. The chromosome is approximately 50 map units in both wild-type and rec-1 homozygotes, however, the distribution of exchanges is very different in rec-1. Map distances expand across the gene cluster and contract near the right end of the chromosome, resulting in a genetic map more consistent with the physical map. Mutations in two other genes, him-6 and him-14, also disrupted the distribution of exchanges. Unlike rec-1, individuals homozygous for him-6 and him-14 had an overall reduction in the amount of crossing over accompanied by a high frequency of nondisjunction and reduced egg hatching. In rec-1; him-6 and rec-1; him-14 homozygotes the frequency of crossing over was characteristic of the Him mutant phenotype, whereas the distribution of the reduced number of exchanges was characteristic of the Rec-1 pattern. It appears that these gene products play a role in establishing the meiotic pattern of exchange events.
Soybean resistance genes specific for different Pseudomonas syringae avirulence genes are allelic, or closely linked, at the RPG1 locus.
Authors: Ashfield T , Keen N T , Buzzell R I , Innes R W
Published: January 2021

RPG1 and RPM1 are disease resistance genes in soybean and Arabidopsis, respectively, that confer resistance to Pseudomonas syringae strains expressing the avirulence gene avrB. RPM1 has recently been demonstrated to have a second specificity, also conferring resistance to P. syringae strains expressing avrRpm1. Here we show that alleles, or closely linked genes, exist at the RPG1 locus in soybean that are specific for either avrB or avrRpm1 and thus can distinguish between these two avirulence genes.
Evolution of Coenzyme B12 Synthesis Among Enteric Bacteria: Evidence for Loss and Reacquisition of a Multigene Complex
Authors: Lawrence Jeffrey G , Roth John R
Published: January 2021

We have examined the distribution of cobalamin (coenzyme B12) synthetic ability and cobalamin-dependent metabolism among enteric bacteria. Most species of enteric bacteria tested synthesize cobalamin under both aerobic and anaerobic conditions and ferment glycerol in a cobalamin-dependent fashion. The group of species including Escherichia coli and Salmonella typhimurium cannot ferment glycerol. E. coli strains cannot synthesize cobalamin de novo, and Salmonella spp. synthesize cobalamin only under anaerobic conditions. In addition, the cobalamin synthetic genes of Salmonella spp. (cob) show a regulatory pattern different from that of other enteric taxa tested. We propose that the cobalamin synthetic genes, as well as genes providing cobalamin-dependent diol dehydratase, were lost by a common ancestor of E. coli and Salmonella spp. and were reintroduced as a single fragment into the Salmonella lineage from an exogenous source. Consistent with this hypothesis, the S. typhimurium cob genes do not hybridize with the genomes of other enteric species. The Salmonella cob operon may represent a class of genes characterized by periodic loss and reacquisition by host genomes. This process may be an important aspect of bacterial population genetics and evolution.
Mutations Modulating Raf Signaling in Drosophila Eye Development
Authors: Dickson Barry J , van der Straten Alexandra , Domínguez María , Hafen Ernst
Published: January 2021

The R7 fate is specified during Drosophila eye development by an inductive signal transduced intracellularly via the Raf kinase. We have performed a genetic screen for dominant mutations that alter the efficiency with which cells respond to a constitutively activated Raf kinase. Such mutations may affect genes involved in signal transduction downstream of Raf. We have isolated 44 mutations that define eight genes. One of these encodes a mitogen-activated protein kinase homologue; another is a putative target gene of this signaling pathway. We present the results of this screen in detail, as well as a preliminary genetic analysis of the six loci still to be characterized molecularly.
Time-Series Analysis of Seasonal Changes of the O Inversion Polymorphism of Drosophila subobscura
Authors: Rodríguez-Trelles Francisco , Alvarez Gonzalo , Zapata Carlos
Published: January 2021

We have studied seasonal variation (spring, early summer, last summer and autumn) of inversion polymorphisms of the O chromosome of Drosophila subobscura in a natural population over 15 years. The length of the study allowed us to investigate the temporal behavior (short-term seasonal changes and long-term directional trends) of the O arrangements by the powerful statistical method of time series analysis. It is shown that the O inversion polymorphisms varied on two different time scales: short-term seasonal changes repeated over the years superimposed on long-term directional trends. All the common arrangements (O3+4+7,  OST,  O3+4 and O3+4+8) showed significant cyclic seasonal changes, and all but one of these arrangements (O3+4+7) showed significant long-term trends. Moreover, the degree of seasonality was different for different arrangements. Thus, O3+4+7 and OST showed the highest seasonality, which accounted for ∼61 and 47% of their total variances, respectively. The seasonal changes in the frequencies of chromosome arrangements were significantly associated with the seasonal variation of the climate (temperature, rainfall, humidity and insolation). In particular, O3+4+7 and OST, the arrangements with the greatest seasonal component, showed the strongest association with all climatic factors investigated, especially to the seasonal changes of extreme temperature and humidity.
Removal of a Mig1p Binding Site Converts a MAL63 Constitutive Mutant Derived by Interchromosomal Gene Conversion to Glucose Insensitivity
Authors: Wang Jianfan , Needleman Richard
Published: January 2021

Maltose fermenting strains of Saccharomyces cerevisiae have one or more complex loci called MAL. Each locus comprises at least three genes: MALx1 encodes maltose permease, MALx2 encodes maltase, and MALx3 encodes an activator of MALxl and MALx2 (x denotes one of five MAL loci, with x = 1, 2, 3, 4, or 6). The MAL43c allele is constitutive and relatively insensitive to glucose repression. To understand better this unique phenotype of MAL43c, we have isolated several MAL63c constitutive mutants from a MAL6 strain. All constitutive mutants remain glucose repressible, and all have multiple amino acid substitutions in the C-terminal region, now making this region of Mal63cp similar to that of Mal43cp. These changes have been generated by gene conversion, which transfers DNA from the telomeres of chromosome II and chromosome III or XVI to chromosome VIII (MAL6). The removal of a Mig1p binding site from the MAL63c promoter leads to a loss of glucose repression, imitating the phenotype of MAL43c. Conversely, addition of a Mig1p binding site to the promoter of MAL43c converts it to glucose sensitivity. Mig1p modulation of Mal63p and Ma143p expression therefore plays a substantial role in glucose repression of the MAL, genes.