bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Evaluation of Candidate Genes for the Mom1 Modifier of Intestinal Neoplasia in Mice
Authors: Gould Karen A , Luongo Cindy , Moser Amy R , McNeley Melanie K , Borenstein Natalie , Shedlovsky Alexandra , Dove William F , Hong Karen , Dietrich William F , Lander Eric S
Published: January 2021

As genetic mapping of quantitative trait loci (QTL) becomes routine, the challenge is to identify the underlying genes. This paper develops rigorous genetic tests for evaluation of candidate genes for a QTL, involving determination of allelic status in inbred strains and fine-structure genetic mapping. For the Mom1 modifier of intestinal adenomas caused by ApcMin, these tests are used to evaluate two candidate genes: Pla2g2a, a secretory phospholipase, and Rap1GAP, a GTPase activating protein. Rap1GAP passes the first test but is excluded by a single fine-structure recombinant. Pla2g2a passes both tests and is a strong candidate for Mom1. Significantly, we also find that ApcMin-induced adenomas remain heterozygous for the Mom1 region, consistent with Mom1 acting outside the tumor lineage and encoding a secreted product.
Interactions of liguleless1 and liguleless2 Function During Ligule Induction in Maize
Authors: Harper Lisa , Freeling Michael
Published: January 2021

The maize ligule is an adaxial membranous structure on the leaf that develops at the boundary of the sheath and blade. The ligule and the associated auricle are dispensable structures, amenable to genetic manipulation. We present here a genetic analysis of liguleless1 (lg1) and liguleless2 (lg2), the two genes known to be uniquely necessary for ligule and auricle development. We show that both reference mutant alleles, lg1-R and lg2-R, are null alleles. The double mutant phenotype suggests that lg1 and lg2 act in the same pathway. Indeed, the dosage of a functional allele at either gene affects the null phenotype of the other. While lg1 function has previously been shown to be cell-autonomous, here we show that the lg2-R phenotype is cell-nonautonomous, suggesting lg1 and lg2 play different roles in the liguleauricle induction mechanism. We present a model in which early lg2 function specifies the precise position where ligule and auricle will develop. Later lg2 function interacts with lg1 function (either directly or indirectly) to transmit and receive a make-ligule-make-auricle inductive signal.
Chromosomal Homology and Molecular Organization of Muller's Elements D and E in the Drosophila repleta Species Group
Authors: María José , Segarra Carmen , Ruiz Alfredo
Published: January 2021

Thirty-three DNA clones containing protein-coding genes have been used for in situ hybridization to the polytene chromosomes of two Drosophila repleta group species, D. repleta and D. buzzatii. Twenty-six clones gave positive results allowing the precise localization of 26 genes and the tentative identification of another nine. The results were fully consistent with the currently accepted chromosomal homologies and in no case was evidence for reciprocal translocations or pericentric inversions found. Most of the genes mapped to chromosomes 2 and 4 that are homologous, respectively, to chromosome arms 3R and 3L of D. melanogaster (Muller's elements E and D). The comparison of the molecular organization of these two elements between D. melanogaster and D. repleta (two species that belong to different subgenera and diverged some 62 million years ago) showed an extensive reorganization via paracentric inversions. Using a maximum likelihood procedure, we estimated that 130 paracentric inversions have become fixed in element E after the divergence of the two lineages. Therefore, the evolution rate for element E is approximately one inversion per million years. This value is comparable to previous estimates of the rate of evolution of chromosome X and yields an estimate of 4.5 inversions per million years for the whole Drosophila genome.
Trans-Suppression of Terminal Deficiency-Associated Position Effect Variegation in a Drosophila Minichromosome
Authors: Donaldson Kathryn M , Karpen Gary H
Published: January 2021

Position effect variegation (PEV) is the clonal inactivation of euchromatic or heterochromatic genes that are abnormally positioned within a chromosome. PEV can be influenced by modifiers in trans, including single gene mutations and the total amount of heterochromatin present in the genome. Terminal deletions of a Drosophila minichromosome (Dp1187) dramatically increase PEV of a yellow  + body-color gene located in cis, even when the terminal break is >100 kb distal to the yellow gene. Here we demonstrate that terminal deficiency-associated PEV can be suppressed by the presence of a second minichromosome, a novel phenomenon termed “trans-suppression.” The chromosomal elements responsible for trans-suppression were investigated using a series of minichromosomes with molecularly characterized deletions and inversions. The data suggest that trans-suppression does not involve communication between transcriptional regulatory elements on the homologues, a type of transvection known to act at the yellow locus. Furthermore, trans-suppression is not accomplished by titration through the addition of extra centric heterochromatin, a general mechanism for PEV suppression. We demonstrate that trans-suppression is disrupted by significant changes in the structure of the suppressing minichromosome, including deletions of the yellow region and centric heterochromatin, and large inversions of the centric heterochromatin. We conclude that chromosome pairing plays an important role in trans-suppression and discuss the possibility that terminal deficiency-associated PEV and trans-suppression reflect changes in nuclear positioning of the chromosomes and the gene, and/or the activity and distribution of telomere-binding proteins.
Epistasis for Three Grain Yield Components in Rice (Oryxa sativa L.)
Authors: Li Zhikang , Pinson Shannon R M , Park William D , Paterson Andrew H , Stansel James W
Published: January 2021

The genetic basis for three grain yield components of rice, 1000 kernel weight (KW), grain number per panicle (GN), and grain weight per panicle (GWP), was investigated using restriction fragment length polymorphism markers and F4 progeny testing from a cross between rice subspecies japonica (cultivar Lemont from USA) and indica (cv. Teqing from China). Following identification of 19 QTL affecting these traits, we investigated the role of epistasis in genetic control of these phenotypes. Among 63 markers distributed throughout the genome that appeared to be involved in 79 highly significant (P < 0.001) interactions, most (46 or 73%) did not appear to have “main” effects on the relevant traits, but influenced the trait(s) predominantly through interactions. These results indicate that epistasis is an important genetic basis for complex traits such as yield components, especially traits of low heritability such as GN and GWP. The identification of epistatic loci is an important step toward resolution of discrepancies between quantitative trait loci mapping and classical genetic dogma, contributes to better understanding of the persistence of quantitative genetic variation in populations, and impels reconsideration of optimal mapping methodology and marker-assisted breeding strategies for improvement of complex traits.
Evolution of Pulmonate Gastropod Mitochondrial Genomes: Comparisons of Gene Organizations of Euhadra, Cepaea and Albinaria and Implications of Unusual tRNA Secondary Structures
Authors: Yamazaki Nika , Ueshima Rei , Terrett Jonathan A , Yokobori Shin-ichi , Kaifu Masayuki , Segawa Ryoko , Kobayashi Takanori , Numachi Ken-ichi , Ueda Takuya , Nishikawa Kazuya , Watanabe Kimitsuna , Thomas Richard H
Published: January 2021

Complete gene organizations of the mitochondrial genomes of three pulmonate gastropods, Euhadra herklotsi, Cepaea nemoralis and Albinaria coerulea, permit comparisons of their gene organizations. Euhadra and Cepaea are classified in the same superfamily, Helicoidea, yet they show several differences in the order of tRNA and protein coding genes. Albinaria is distantly related to the other two genera but shares the same gene order in one part of its mitochondrial genome with Euhadra and in another part with Cepaea. Despite their small size (14.1 – 14.5 kbp), these snail mtDNAs encode 13 protein genes, two rRNA genes and at least 22 tRNA genes. These genomes exhibit several unusual or unique features compared to other published metazoan mitochondrial genomes, including those of other molluscs. Several tRNAs predicted from the DNA sequences possess bizarre structures lacking either the T stem or the D stem, similar to the situation seen in nematode mt-tRNAs. The acceptor stems of many tRNAs show a considerable number of mismatched basepairs, indicating that the RNA editing process recently demonstrated in Euhadra is widespread in the pulmonate gastropods. Strong selection acting on mitochondrial genomes of these animals would have resulted in frequent occurrence of the mismatched basepairs in regions of overlapping genes.
An Experimental Test for Synergistic Epistasis and Its Application in Chlamydomonas
Authors: de Visser J A G M Arjan , Hoekstra Rolf F , van den Ende Herman
Published: January 2021

Theoretically, one of the most general benefits of sex is given by its function in facilitating selection against deleterious mutations. This advantage of sex may be deterministic if deleterious mumtiom affect the fitness of an individual in a synergistic way, i.e., if mutations increase each others' negative fitness effect. We present a new test for synergistic epistasis that considers the skewnessof the log fitness distribution of offspring from a cross. We applied this test to data of the unicellular alga Chlamydomonas moewussii. For this purpose, two crosses were made: one between two strains that are presumed to have accumulated slightly deleterious mutations, the other between two strains without a history of mutation accumulation. Fitness was measured by estimating the two parameters of logistic growth in batch culture, the maximum growth rate (r) and the carrying capacity (K). The finding of a negatively skewed distribution for K in the accumulation cross suggests synergism between mutations affecting the carrying capacity, while the absence of skewness for r in both crosses is consistent with independent effects of mutations affecting this parameter. The results suggest a possible alternative explanation for the general observation that sex is related to constant environments, where selection on K predominates, while asexual reproduction is found in more variable environments, where selection on r is more important.
Genetics of a Pheromonal Difference Affecting Sexual Isolation Between Drosophila mauritiana and D. sechellia
Authors: Coyne Jerry A , Charlesworth Brian
Published: January 2021

Females of the sibling species Drosophila sechellia and D. mauritiana differ in their cuticular hydrocarbons: the predominant compound in D. sechellia is 7,11-heptacosadiene (7,11-HD), while that in D. mauritiana is 7-tricosene (7-T). We investigate the genetic basis of this difference and its involvement in reproductive isolation between the species. Behavioral studies involving hydrocarbon transfer suggest that these compounds play a large role in the sexual isolation between D. mauritiana males and D. sechellia females, while sexual isolation in the reciprocal hybridization results more from differences in female behavior than hydrocarbons. This interspecific difference in hydrocarbon profile is due to evolutionary change at a minimum of six loci, all on the third chromosome. The localization of evolutionary change to the third chromosome has been seen in every other genetic analysis of female hydrocarbon differences in the D. melanogaster group. We suggest that the high 7,11-HD phenotype seen in two species evolved twice independently from ancestors having the high 7-T phenotype, and that the recurrent third-chromosome effects are evolutionary convergences that may be due to a concentration of “hydrocarbon genes” on that chromosome.
The Developmental Genetics of Hybrid Inviability: A Mitotic Defect in Drosophila Hybrids
Authors: Orr H Allen , Madden Laurence D , Coyne Jerry A , Goodwin Renee , Hawley R Scott
Published: January 2021

We report studies of the developmental basis of hybrid inviability in the Drosophila melanogaster complex. The pathology of these hybrids closely resembles that of mitotic mutants in D. melanogaster. We use mosaic and cytological analyses to show that hybrid male inviability is associated with, and probably caused by, a defect in mitotic cell division. In the mosaic study, we find that male clones produced in otherwise female hybrids are not cell lethal but are very small, probably reflecting defects in mitotic proliferation. Cytological inspection of larval neuroblasts reveals a profound mitotic defect in hybrids: chromosomes show a near-complete failure to condense even after 2 hr of incubation in colchicine. Both the defect in clonal proliferation and in chromatin condensation are rescued by mutations known to rescue normally inviable hybrid males. We present a simple model in which hybrid inviability is partly or entirely caused by a mitotic defect; this defect is, in turn, caused by an interaction between the Hybrid male rescue (Hmr) locus of D. melanogaster and autosomal gene(s) from D. melanogaster's sister species.
Imperfect Genes, Fisherian Mutation and the Evolution of Sex
Authors: Peck Joel R , Barreau Guillaume , Heath Simon C
Published: January 2021

In this paper we present a mathematical model of mutation and selection that allows for the coexistence of multiple alleles at a locus with very small selective differences between alleles. The model also allows for the determination of fitness by multiple loci. Models of this sort are biologically plausible. However, some previous attempts to construct similar models have assumed that all mutations produce a decrease in fitness, and this has led to a tendency for the average fitness of population members to decline when population numbers are finite. In our model we incorporate some of the ideas of R. A. Fisher, so that both deleterious and beneficial mutations are possible. As a result, average fitness tends to approach a stationary distribution. We have used computer simulation methods to apply the Fisherian mutation model to the problem of the evolution of sex and recombination. The results suggest that sex and recombination can provide very large benefits in terms of average fitness. The results also suggest that obligately sexual species will win ecological competitions with species that produce a substantial fraction of their offspring asexually, so long as the number of sites under selection within the genomes of the competing species is not too small and the population sizes are not too large. Our model focuses on fertility selection in an hermaphroditic plant. However, the results are likely to generalize to a wide variety of other situations as well.
Multilocus and Multitrait Measures of Differentiation for Gene Markers and Phenotypic Traits
Authors: Kremer Antoine , Zanetto Anne , Ducousso Alexis
Published: January 2021

Multilocus measures of differentiation taking into account gametic disequilibrium are developed. Even if coupling and repulsion heterozygotes cannot be separated at the multilocus level, a method is given to calculate a composite measure of differentiation (CFst) at the zygotic level, which accounts for allelic associations combining both gametic and nongametic effects. Mean and maximum differentiations may be relevant when multilocus measures are computed. Maximum differentiation is the highest eigenvalue of the Fst matrix, whereas mean differentiation corresponds to the mean value of all eigenvalues of the Fst matrix. Gametic disequilibrium has a stronger effect on maximum differentiation than on mean differentiation and takes into account the anisotropy that may exist between within- and between-population components of disequilibria. Multilocus mean and maximum differentiation are calculated for a set of 81 Quercus petraea (sessile oak) populations assessed with eight allozyme loci and two phenotypic traits (bud burst and height growth). The results indicate that maximum differentiation increases as more loci (traits) are considered whereas mean differentiation remains constant or decreases. Phenotypic traits exhibit higher population differentiation than allozymes. The applications and uses of mean and maximum differentiations are further discussed.
Increased Length of Long Terminal Repeats Inhibits Ty1 Transposition and Leads to the Formation of Tandem Multimers
Authors: Lauermann Vit , Hermankova Monika , Boeke Jef D
Published: January 2021

The Ty1 retrotransposon of Saccharomyces cerevisiae is bounded by long-terminal repeats (LTRs). We have constructed a variety of Ty1 elements in which the LTR length has been increased from the normal length of 334 bp to >2 kb. Although small insertions in the LTR have minimal effects on transposition frequency, larger insertions dramatically reduce it. Nevertheless, elements with long LTRs are incorporated into the genome at a low frequency. Most of these rare insertion events represent Ty1 tandem (head to tail) multimers.
Multilocus Evolution in Fire Ants: Effects of Selection, Gene Flow and Recombination
Authors: Ross Kenneth G
Published: January 2021

The reproductive success of individual fire ant queens (Solenopsis invicta) previously has been shown to be strongly influenced by their genotype at a single enzyme-encoding gene, designated Pgm-3. This paper presents evidence that a second, tightly linked gene, designated Gp-9, is under similarly strong selection in these ants. Selection appears to act independently on the two genes and is detectable in only one of the two social forms of this species (the “polygyne” social form, in which nests contain multiple fertile queens). Strong directional selection on Pgm-3 in this form involves worker destruction of all queens with genotype Pgm-3AA before they reproduce. Selection on Gp-9 is more complex, involving both lethality of all Gp-9bb females and a strong or even complete survival advantage to reproductive queens with the heterozygous genotype Gp-9Bb. Pgm-3 and Gp-9 are tightly linked (rf = 0.0016) and exhibit strong gametic phase disequilibrium in introduced populations in the U.S. This disequilibrium seems not to have stemmed from the founder event associated with the introduction, because the same associations of alleles found in the U S. apparently occur also in two native populations in Argentina. Rather, selection acting independently on Pgm-3 and Gp-9, in conjunction with gene flow from the alternate, “monogyne” social form (in which nests contain a single fertile queen), may explain the origin of disequilibrium between the two loci in polygyne fire ants.
Lack of Degeneration of Loci on the Neo-Y Chromosome of Drosophila americana americana
Authors: Charlesworth B , Charlesworth D , Hnilicka J , Yu A , Guttman D S
Published: January 2021

The extent of genetic degeneration of the nec-Y chromosome of Drosophila americana americana has been investigated. Three loci, coding for the enzymes enolase, phosphoglycerate kinase and alcohol dehydrogenase, have been localized to chromosome 4 of D. a. americana, which forms the neo-Y and neo-X chromosomes. Crosses between D. a. americana, and D. virilis or D. montana showed that the loci coding for these enzymes carry active alleles on the neo-Y chromosome in all wild-derived strains of americana that were tested. Intercrosses between a genetically marked stock of virilis and strains of americana were carried out, creating F3 males that were homozygous for sections of the neo-Y chromosome. The sex ratios in the F3 generation of the intercrosses showed that no lethal alleles have accumulated on any of the neo-Y chromosomes tested. There was evidence for more minor reductions in fitness, but this seems to be mainly caused by deleterious alleles that are specific to each strain. A similar picture was provided by examination of the segregation ratios of two marker genes among the F3 progeny. Overall, the data suggest that the neo-Y chromosome has undergone very little degeneration, certainly not to the extent of having lost the functions of vital genes. This is consistent with the recent origin of the neo-Y and neo-X chromosomes, and the slow rates at which the forces that cause Y chromosome degeneration are likely to work.
The mup-4 Locus in Caenorhabditis elegans Is Essential for Hypodermal Integrity, Organismal Morphogenesis and Embryonic Body Wall Muscle Position
Authors: Gatewood Beth K , Bucher Elizabeth A
Published: January 2021

mup-4 is a member of a set of genes essential for correct embryonic body wall muscle cell positions in Caenorhabditis elegans. The mup-4 phenotype is variably expressed and three discrete arrest phenotypes arise during the phase of embryonic development when the worm elongates from a ball of cells to its worm shape (organismal morphogenesis). Mutants representing two of the phenotypic classes arrest without successful completion of elongation. Mutants of the third phenotypic class arrest after completion of elongation. Mutants that arrest after elongation display profound dorsal and ventral body wall muscle cell position abnormalities and a characteristic kinked body shape (the Mup phenotype) dueto the muscle cell position abnormalities. Significantly, genetic mosaic analysis of mup-4 mutants demonstrates that mup-4 gene function is essential in the AB lineage, which generates most of the hypodermis (epidermis), a tissue with which muscle interacts. Consistent with the genetic mosaic data, phenotypic characterizations reveal that mutants have defects in hypodermal integrity and morphology. Our analyses support the conclusion that mup-4 is essential for hypodermal function and that this function is necessary for organismal morphogenesis and for the maintenance of body wall muscle position.
Heterochromatic Stellate Gene Cluster in Drosophila melanogaster: Structure and Molecular Evolution
Authors: Tulin Alexei V , Kogan Galina L , Filipp Dominik , Balakireva Maria D , Gvozdev Vladimir A
Published: January 2021

The 30-kb cluster comprising close to 20 copies of tandemly repeated Stellate genes was localized in the distal heterochromatin of the X chromosome. Of 10 sequenced genes, nine contain undamaged open reading frames with extensive similarity to protein kinase CK2 β-subunit; one gene is interrupted by an insertion. The heterochromatic array of Stellate repeats is divided into three regions by a 4.5-kb DNA segment of unknown origin and a retrotransposon insertion: the A region (∼14 Stellate genes), the adjacent B region (approximately three Stellate genes), and the C region (about four Stellate genes). The sequencing of Stellate copies located along the discontinuous cluster revealed a complex pattern of diversification. The lowest level of divergence was detected in nearby Stellate repeats. The marginal copies of the A region, truncated or interrupted by an insertion, escaped homogenization and demonstrated high levels of divergence. Comparison of copies in the B and C regions, which are separated by a retrotransposon insertion, revealed a high level of diversification. These observations suggest that homogenization takes place in the Stellate cluster, but that inserted sequences may impede this process.
Context-Dependent Survival Differences Among Electrophoretic Genotypes in Natural Populations of the Marine Bivalve Spisula ovalis
Authors: David Patrice , Jarne Philippe
Published: January 2021

We investigated the relationships between allozyme genotypes at nine polymorphic loci and survival in a natural population of the bivalve Spisula ovalis sampled on three occasions (1993, 1994, and 1995) in three different sites (2855 individuals analyzed). This species displays annual growth lines allowing identification of annual cohorts. Therefore we could avoid cohort mixing, a frequent bias in such studies, and evaluate the consistency of the observed effects across cohorts and sites. Significant viability differences were observed both among alleles and between heterozygotes and homozygotes at some loci. Multiple-locus heterozygosity was positively correlated with viability in the 1993–1994 period, but not in the 1994–1995 interval. The observed selective effects were significantly dependent on the cohort and the site considered. A bibliographic survey suggests that such variability is a common feature of studies analyzing heterozygosity-survival relationships. Two explanations are consistent with our results. First, allozyme genotypes may have direct effects on viability that interact with subtle environmental variation in a complex and unpredictable way. Second, allozyme genotypes may be transiently associated with other viability genes responsible for heterotic effects. In any case, the results militate against allozyme loci being themselves consistently overdominant for viability in natural populations.
Karyotype Variability in Yeast Caused by Nonallelic Recombination in Haploid Meiosis
Authors: Loidl Josef , Nairz Knud
Published: January 2021

Chromosomes of altered size were found in the meiotic products of a haploid Saccharomyces cerevisiae strain by pulsed field gel electrophoretic separation of whole chromosomes. About 7% of haploid meioses produced chromosomes that differed by ≥10 kb from their wild-type counterparts. Chromosomes most often became enlarged or shortened due to recombination events between sister chromatids at nonallelic sequences. By this mechanism chromosome III acquired tandem arrays of up to eight extra copies of the ∼100 kb MAT-HMR segment during repeated rounds of haploid meioses. Enlarged chromosomes III were unstable and changed their size during meiosis more often than remaining unchanged. Altered chromosomes appeared also as the products of intrachromatid recombination and of reciprocal translocations caused by ectopic recombination between nonhomologous chromosomes. In diploid meiosis, chromosomes of altered size occurred at least 10 times less frequently, whereas in mitotic cultures cells with altered karyotypes were virtually absent. The results show that various forms of ectopic recombination are promoted by the absence of allelic homologies.
Enhanced Deletion Formation by Aberrant DNA Replication in Escherichia coli
Authors: Saveson Catherine J , Lovett Susan T
Published: January 2021

Repeated genes and sequences are prone to genetic rearrangements including deletions. We have investigated deletion formation in Escherichia coli strains mutant for various replication functions. Deletion was selected between 787 base pair tandem repeats carried either on a ColE1-derived plasmid or on the E. coli chromosome. Only mutations in functions associated with DNA Polymerase III elevated deletion rates in our assays. Especially large increases were observed in strains mutant in dnaQ the ϵ editing subunit of Pol III, and dnuB, the replication fork helicase. Mutations in several other functions also altered deletion formation: the α polymerase (dnaE), the γ clamp loader complex (holC, dnaX), and the β clamp (dnaN) subunits of Pol III and the primosomal proteins, dnaC and priA. Aberrant replication stimulated deletions through several pathways. Whereas the elevation in dnaB strains was mostly recA- and lexA-dependent, that in dnaQ strains was mostly recA- and lexA-independent. Deletion product analysis suggested that slipped mispairing, producing monomeric replicon products, may be preferentially increased in a dnaQ mutant and sister-strand exchange, producing dimeric replicon products, may be elevated in dnaE mutants. We conclude that aberrant Polymerase III replication can stimulate deletion events through several mechanisms of deletion and via both recA-dependent and independent pathways.
Long-Term Experimental Evolution in Escherichia coli. VI. Environmental Constraints on Adaptation and Divergence
Authors: Travisano Michael
Published: January 2021

The effect of environment on adaptation and divergence was examined in two sets of populations of Escherichia coli selected for 1000 generations in either maltose- or glucose-limited media. Twelve replicate populations selected in maltose-limited medium improved in fitness in the selected environment, by an average of 22.5%. Statistically significant among-population genetic variation for fitness was observed during the course of the propagation, but this variation was small relative to the fitness improvement. Mean fitness in a novel nutrient environment, glucose-limited medium, improved to the same extent as in the selected environment, with no statistically significant among-population genetic variation. In contrast, 12 replicate populations previously selected for 1000 generations in glucose-limited medium showed no improvement, as a group, in fitness in maltose-limited medium and substantial genetic variation. This asymmetric pattern of correlated responses suggests that small changes in the environment can have profound effects on adaptation and divergence.
Genotype Selection to Rapidly Breed Congenic Strains
Authors: Weil Michael M , Brown Barry W , Serachitopol Dan M
Published: January 2021

Congenic strains can now be constructed guided by the transmission of DNA markers. This allows not only selection for transmission of a desired, donor-derived differential region but also selection against the transmission of unwanted donor origin genomic material. The additional selection capacity should allow congenic strains to be produced in fewer generations than is possible with random backcrosses. Here, we consider modifications of a standard backcross breeding scheme to produce congenic mice by the inclusion of genotype-based selective breeding strategies. Simulation is used to evaluate the consequences of each strategy on the number of chromosomes that contain unwanted, donor-derived genetic material and the average length of this unwanted donor DNA for each backcross generation. Our prototypic strategy was to choose a single mouse to sire each generation using criteria designed to select against the transmission of chromosomes, other than the one containing the replacement genomic region, that contain any donor origin sequence at all. This chromosome elimination strategy resulted in an average of 16.4 chromosomes free of donor DNA in mice of the third backcross (N3) generation. A strategy based solely on positive selection for the replacement region required six backcross generations to achieve the same results.
A Comparison of Population Differentiation Across Four Classes of Gene Marker in Limber Pine (Pinus flexilis James)
Authors: Latta Robert G , Mitton Jeffry B
Published: January 2021

We examined genetic differentiation among seven populations of limber pine using four classes of gene marker. Among-population differentiation was much higher for maternally inherited mitochondrial DNA polymorphisms than for paternally inherited chloroplast DNA, indicating that wind-dispersed pollen is the main agent of gene flow. Chloroplast DNA differentiation is consistent with gene flow estimated in a prior paternity analysis. Using the estimates of seed and pollen flow derived from mtDNA and cpDNA differentiation, we predicted the value of Fst expected at nuclear loci. Allelic frequency differentiation at seven allozyme loci was relatively homogeneous across loci and consistent with the level of differentiation predicted from the organellar haplotypes. By contrast four of the nine randomly applied polymorphic DNA (RAPD) markers we examined were more strongly differentiated than this prediction, suggesting the action of diversifying selection. However, the differentiated RAPDs and mtDNA were concordant in dividing the populations into two groups, suggesting some historical division. Simulations show that such historical division can increase the interlocus variance in Fst but neither a historical nor an equilibrium model could account for the joint distribution of Fst estimates across both allozyme and RAPD loci. Thus at least one group of loci appears to be experiencing natural selection.
The Exact Test for Cytonuclear Disequilibria
Authors: Basten Christopher J , Asmussen Marjorie A
Published: January 2021

We extend the analysis of the statistical properties of cytonuclear disequilibria in two major ways. First, we develop the asymptotic sampling theory for the nonrandom associations between the alleles at a haploid cytoplasmic locus and the alleles and genotypes at a diploid nuclear locus, when there are an arbitrary number of alleles at each marker. This includes the derivation of the maximum likelihood estimators and their sampling variances for each disequilibrium measure, together with simple tests of the null hypothesis of no disequilibrium. In addition to these new asymptotic tests, we provide the first implementation of Fisher's exact test for the genotypic cytonuclear disequilibria and some approximations of the exact test. We also outline an exact test for allelic cytonuclear disequilibria in multiallelic systems. An exact test should be used for data sets when either the marginal frequencies are extreme or the sample size is small. The utility of this new sampling theory is illustrated through applications to recent nuclear-mtDNA and nuclear-cpDNA data sets. The results also apply to population surveys of nuclear loci in conjunction with markers in cytoplasmically inherited microorganisms.
Microsatellite Instability in Yeast: Dependence on the Length of the Microsatellite
Authors: Wierdl Monika , Dominska Margaret , Petes Thomas D
Published: January 2021

One of the most common microsatellites in eukaryotes consists of tandem arrays [usually 15-50 base pairs (bp) in length] of the dinucleotide GT. We examined the rates of instability for poly GT tracts of 15, 33, 51, 99 and 105 bp in wild-type and mismatch repair-deficient strains of Saccharomyces cerevisiae. Rates of instability increased more than two orders of magnitude as tracts increased in size from 15 to 99 bp in both wild-type and msh2 strains. The types of alterations observed in long and short tracts in wild-type strains were different in two ways. First, tracts ≥51 bp had significantly more large deletions than tracts ≤33 bp. Second, for the 99- and 105-bp tracts, almost all events involving single repeats were additions; for the smaller tracts, both additions and deletions of single repeats were common.
Polymorphism for Y-Linked Suppressors of sex-ratio in Two Natural Populations of Drosophila mediopunctata
Authors: Carvalho Antonio Bernardo , Vaz Suzana Casaccia , Klaczko Louis Bernard
Published: January 2021

In several Drosophila species there is a trait known as “sex-ratio”: males carrying certain X chromosomes (called “SR”) produce female biased progenies due to X-Y meiotic drive. In Drosophila mediopunctata this trait has a variable expression due to Y-linked suppressors of sex-ratio expression, among other factors. There are two types of Y chromosomes (suppressor and nonsuppressor) and two types of SR chromosomes (suppressible and unsuppressible). Sex-ratio expression is suppressed in males with the SRsuppressible/Ysuppressor genotype, whereas the remaining three genotypes produce female biased progenies. Now we have found that ∼10–20% of the Y chromosomes from two natural populations 1500 km apart are suppressors of sex-ratio expression. Preliminary estimates indicate that Ysuppressor has a meiotic drive advantage of 6% over Ynonsuppressor. This Y polymorphism for a nonneutral trait is unexpected under current population genetics theoly. We propose that this polymorphism is stabilized by an equilibrium between meiotic drive and natural selection, resulting from interactions in the population dynamics of X and Y alleles. Numerical simulations showed that this mechanism may stabilize nonneutral Y polymorphisms such as we have found in D. mediopunctata.
Hybridogenetic Reproduction and Maternal Ancestry of Polyploid Iberian Fish: The Tropidophoxinellus alburnoides Complex
Authors: Carmona José A , Sanjur Oris I , Doadrio Ignacio , Machordom Annie , Vrijenhoek Robert C
Published: January 2021

Iberian minnows collectively known as the Tropidophoxinellus alburnoides Steindachner complex comprise diploid and polyploid forms with highly female biased sex ratios. Previous investigators suggested that all-female clonal reproduction and interspecific hybridization may occur in this complex. We examined nuclear (allozymes) and cytoplasmic genes (mtDNA) to assess the evolutionary origins, relationships, and reproductive modes of T. alburnoides from western Spain. The multi-locus allozyme data clearly revealed the hybrid nature of all polyploid forms of this fish and some diploid forms as well. Diagnostic markers identified fish from the genus Leuciscus as the paternal ancestor of hybrids in the Duero and Guadiana River Basins. Additionally, analysis of nuclear markers revealed that hybridogenetic reproduction occurs in the diploid and triploid hybrids. The hybrids fully express the paternal Leuciscus genome and then discard it during oogenesis. Hybridogenetic ova contain only maternal nuclear genes and mtDNA from a non-hybrid T. alburnoides ancestor. Apparently diploid and triploid hybrids of T. alburnoides persist as sperm parasites on males of a sexually reproducing Leuciscus host species.
Megaplasmid and Chromosomal Loci for the PHB Degradation Pathway in Rhizobium (Sinorhizobium) meliloti
Authors: Charles Trevor C , Cai Guo-qin , Aneja Punita
Published: January 2021

Chromosomal and megaplasmid loci that affect the poly-3-hydroxybutyrate (PHB) degradation pathway in Rhizobium meliloti were identified. A clone that restores the ability of certain R. meliloti mutants with defined deletions in megaplasmid pRmeSU47b to use 3-hydroxybutyrate or acetoacetate as the sole carbon source was isolated from a cosmid library of R. meliloti genomic DNA. Tn5 insertion mutagenesis, followed by merodiploid complementation analysis, demonstrated that the locus consists of at least four transcriptional units, bhbA-D. We also identified loci involved in 3-hydroxybutyrate and/or acetoacetate utilization by screening for mutants that had lost the ability to use 3-hydroxybutyrate as the sole carbon source while retaining the ability to use acetate (thus ensuring an intact glyoxylate cycle and gluconeogenic pathway). These mutants fell into four classes, as determined by replicon mobilization experiments and genetic linkage in phage transduction; one class corresponded to the bhb locus on pRmeSU47b, two classes mapped to different regions on the chromosome and the fourth, bdhA, represented by a single mutant, mapped to another pRmeSU47b locus, near bacA. The bdhA mutant is deficient in 3-hydroxybutrate dehydrogenase activity.
A WD Repeat Protein, Rec14, Essential for Meiotic Recombination in Schizosaccharomyces pombe
Authors: Evans David H , Li Ywan Feng , Fox Mary E , Smith Gerald R
Published: January 2021

Mutations in the Schizosaccharomyces pombe rec14 gene reduce meiotic recombination by as much as a factor of 1000 in the three intervals tested on chromosomes I and III. A DNA clone complementing the rec14 mutation was shown by genetic and physical analysis to contain the rec14 gene, which was functional in plasmid-borne inserts as small as 1.4 kb. The rec14 gene contains two exons separated by a 53-bp intron, which was confirmed by analysis of rec14 transcripts. The spliced transcript encodes a protein product of 302 amino acids, which contains six WD repeat motifs found in the G-beta transducin family of proteins and other proteins, including the Saccharomyces cerevisiae Ski8 (Rec103) protein. Although the rec14 transcripts were present in mitotically dividing cells, rec14 mutations had no detectable effect on mitotic recombination. The pattern of expression of rec14 differs from that of previously analyzed S. pombe rec genes. Based upon mutant phenotypes and amino acid sequence similarities, we propose that S. pombe Rec14 is a functional homologue of S. cerevisiae Rec103.
Constitutive Mutations of the Saccharomyces cerevisiae MAL-Activator Genes MAL23, MAL43, MAL63, and mal64
Authors: Gibson Andrew W , Wojciechowicz Lori A , Danzi Sara E , Zhang Bin , Kim Jeong H , Hu Zhen , Michels Corinne A
Published: January 2021

We report the sequence of several MAL-activator genes, including inducible, constitutive, and noninducible alleles of MAL23, MAL43, MAL63, and mal64. Constitutive alleles of MAL23 and MAL43 vary considerably from inducible alleles in their C-terminal domain, with many of the alterations clustered and common to both alleles. The 27 alterations from residues 238–461 of Mal43-C protein are sufficient for constitutivity, but the minimal number of alterations needed for the constitutive phenotype could not be determined. The sequence of mal64, a nonfunctional homologue of MAL63, revealed that Mal64p is 85% identical to Mal63p. Two mutations that activate mal64 and cause constitutivity are nonsense mutations resulting in truncated proteins of 306 and 282 residues. We conclude that the C-terminal region of the MAL-activator, from residues 283–470, contains a maltose-responsive negative regulatory domain, and that extensive mutation or deletion of the entire region causes loss of the negative regulatory function. Additionally, certain sequence elements in the region appear to be necessary for efficient induction of the full-length Mal63 activator protein. These studies highlight the role of ectopic recombination as an important mechanism of mutagenesis of the telomere-associated family of MAL loci.
Paternal Transmission of X-Linked Placental Dysplasia in Mouse Interspecific Hybrids
Authors: Zechner Ulrich , Reule Matthias , Burgoyne Paul S , Schubert Alexis , Orth Annie , Hameister Horst , Fundele Reinald
Published: January 2021

It has previously been shown that abnormal placental development, i.e., hyper- and hypoplasia, occurs in crosses and backcrosses between different mouse (Mus) species. These defects are caused mainly by abnormal growth of the spongiotrophoblast. The precise genetic basis for these placental malformations has not been determined. However, a locus that contributes to the abnormal development (Ihpd: interspecific hybrid placental dysplasia) has been mapped to the X chromosome. The X-chromosomal location of Ihpd and its site of action, that is the spongiotrophoblast, mean that normally only the maternally inherited Ihpd locus is active even in female fetuses. However, by making use of the X-chromosomal inversion In(X)1H, we have produced interspecific hybrid Xp0, in which the active X chromosome was inherited from Mus macedonicus males. In contrast to XX female and XY male conceptuses from this cross, which have hypoplastic placentas, the Xp0 female conceptuses have hyperplastic placentas. This finding supports the view that it is expression of the M. macedonicus Ihpd locus in the spongiotrophoblast that leads to hyperplasia due to an abnormal interaction with M. musculus autosomal loci.
Microsatellite Polymorphism in Natural Populations of the Wild Plant Arabidopsis thaliana
Authors: Innan Hideki , Terauchi Ryohei , Miyashita Naohiko T
Published: January 2021

Variation in repeat number at 20 microsatellite loci of Arabidopsis thaliana was studied in a worldwide sample of 42 ecotypes to investigate the pattern and level of polymorphism in repetitive sequences in natural plant populations. There is a substantial amount of variation at microsatellite loci despite the selfing nature of this plant species. The average gene diversity was 0.794 and the average number of alleles per locus was 10.6. The distribution of alleles was centered around the mean of repeat number at most loci, but could not be regarded as normal. There was a significantly positive correlation between the number of repeats and the amount of variation. For most loci, the observed number of alleles was between the expected values of the infinite allele and stepwise mutation models. The two models were rejected by the sign test. Linkage disequilibrium was detected in 12.1% of the pairwise comparisons between loci. In phylogenetic tree, there was no association between ecotype and geographic origin. This result is consistent with the recent expansion of A. thaliana throughout the world.
Inbreeding Depression and Inferred Deleterious-Mutation Parameters in Daphnia
Authors: Deng Hong-Wen , Lynch Michael
Published: January 2021

Deng and Lynch recently proposed a method for estimating deleterious genomic mutation parameters from changes in the mean and genetic variance of fitness traits upon inbreeding in outcrossing populations. Such observations are readily acquired in cyclical parthenogens. Selfing and life-table experiments were performed for two such Daphnia populations. We observed a significant inbreeding depression and an increase of genetic variance for all traits analyzed. Deng and Lynch's original procedures were extended to estimate genomic mutation rate (U), mean dominance coefficient (h‒), mean selection coefficient (s‒) and scaled genomic mutational variance (Vm/Ve). On average, U^, h‒̂, s‒̂ and V^m∕Vs (^ indicates an estimate) are 0.74, 0.30, 0.14 and 4.6E-4, respectively. For the true values, the U^ and h‒̂ are lower bounds, and s‒̂ and V^m∕Ve, upper bounds. The present U^, h‒̂ and V^m∕Ve are in general concordance with earlier results. The discrepancy between the present V^m∕Ve and that from mutation-accumulation experiments in Drosophila (~0.04) is discussed. It is shown that different reproductive modes do not affect gene frequency at mutation-selection equilibrium if mutational effects on fitness are multiplicative and not completely recessive.
Epistasis in Measured Genotypes: Drosophila P-Element Insertions
Authors: Clark Andrew G , Wang Lei
Published: January 2021

Transposon tagging provides an opportunity to construct large numbers of strains of organisms that differ by single insertional mutations. By scoring the phenotypes of these “measured genotypes,” powerful tests of effects of mutations on phenotypic expression have been performed. Here we extend this approach by constructing with simple crosses all possible two-locus genotypes for each of eight pairs of P-element insertions. Analysis of metabolic phenotypes (fat and glycogen contents, enzyme activities, total protein, and body weight) of the resulting nine genotypes provides direct estimates of additive, dominance, and epistatic effects of the mutations. Nested two-way analysis of variance identified significant epistatic effects in 27% of the tests (35/128 of the trait × P-element combinations). Posterior contrasts were performed to partition the epistatic variance into the four orthogonal components of Cockerham, and the data exhibit a tendency toward additive × dominance and dominance × dominance epistasis, Mutations in this study have epistatic effects on metabolic traits that are on the same order of magnitude as main (additive and dominance) effects. Measured genotypes have been used in other contexts to quantify epistatic effects on phenotypic expression, and these results are also briefly reviewed.