bluuebunny/crossref_metadata_2025_split huggingface dataset:
Homology Requirements for Double-Strand Break-Mediated Recombination in a Phage λ-td Intron Model System
Authors: Parker Monica M , Court Deborah A , Preiter Karen , Belfort Marlene 
Published: January 2021

Abstract
Many group I introns encode endonucleases that promote intron homing by initiating a double-strand break-mediated homologous recombination event. A td intron-phage λ model system was developed to analyze exon homology effects on intron homing and determine the role of the λ 5′–3′ exonuclease complex (Redαβ) in the repair event. Efficient intron homing depended on exon lengths in the 35- to 50-bp range, although homing levels remained significantly elevated above nonbreak-mediated recombination with as little as 10 bp of flanking homology. Although precise intron insertion was demonstrated with extremely limiting exon homology, the complete absence of one exon produced illegitimate events on the side of heterology. Interestingly, intron inheritance was unaffected by the presence of extensive heterology at the double-strand break in wild-type λ, provided that sufficient homology between donor and recipient was present distal to the heterologous sequences. However, these events involving heterologous ends were absolutely dependent on an intact Red exonuclease system. Together these results indicate that heterologous sequences can participate in double-strand break-mediated repair and imply that intron transposition to heteroallelic sites might occur at break sites within regions of limited or no homology.
Genetic Analysis of the Bacteriophage λ attL Nucleoprotein Complex
Authors: MacWilliams Maria P , Gumport Richard I , Gardner Jeffrey F 
Published: January 2021

Abstract
Site-specific recombination in bacteriophage λ involves interactions among proteins required for integration and excision of DNA molecules. We have analyzed the elements required to form an in vivo nucleoprotein complex of integrase (Int) and integration host factor (IHF). Interaction of Int with the core (the site of strand exchange) is stabilized by the flanking arm region of attL. IHF, in addition to Int, is required for efficient Int-core binding. We used the in vivo attL binding assay to characterize several Int variants for their abilities to form stable attL complexes. Substitution of Int active site tyrosine 342 by phenylalanine had no effect on the ability of the protein to form attL complexes. Three other amino acids that are completely conserved in the integrase family of recombinases (arginine 212, histidine 308, and arginine 311) were separately substituted by glutamine, leucine, and histidine, respectively. In each case, the mutant protein was altered in its ability to form attL complexes while retaining its ability to bind to the λ arm-type sites. We propose that, in addition to their role in catalysis, this triad of amino acids helps the Int protein to interact with the λ core sites.
Mutants With Altered Sensitivity to a Calmodulin Antagonist Affect the Circadian Clock in Neurospora crassa
Authors: Suzuki Sakura , Katagiri Satoshi , Nakashima Hideaki 
Published: January 2021

Abstract
Two newly isolated mutant strains of Neurospora crassa, cpz-1 and cpz-2, were hypersensitive to chlorpromazine with respect to mycelial growth but responded differently to the drug with respect to the circadian conidiation rhythm. In the wild type, chlorpromazine caused shortening of the period length of the conidiation rhythm. Pulse treatment with the drug shifted the phase and inhibited light-induced phase shifting in Neurospora. By contrast to the wild type, the cpz-2 strain was resistant to these inhibitory effects of chlorpromazine. Inhibition of cpz-2 function by chlorpromazine affected three different parameters of circadian conidiation rhythm, namely, period length, phase and light-induced phase shifting. These results indicate that the cpz-2 gene must be involved in or related closely to the clock mechanism of Neurospora. By contrast, the cpz-1 strain was hypersensitive to chlorpromazine with respect to the circadian conidiation rhythm.
Physical Map of the Malaria Vector Anopheles gambiae
Authors: della Tome A , Favia G , Mariotti G , Coluzzi M , Mathiopoulos K D 
Published: January 2021

Abstract
Random cDNA clones, cosmid clones and RAPD polymorphic fragments have been localized by in situ hybridization to the ovarian nurse cell polytene chromosomes of the malaria vector Anopheles gambiue. We thus established 85 molecular markers for 110 sites within the whole A. gambiaepolytene chromosome complement. The cDNA clones analyzed were isolated at random, and their exact localizations were determined by in situ hybridization. For 15 of the cDNA clones, a partial nucleotide sequence has been obtained; for nine of them sequence searches in the GenBank database revealed high degrees of similarity with published sequences. The cosmid clones analyzed were obtained as the result of screening with a few of the aforementioned cDNA clones of particular interest, or taken from a small set of randomly isolated cosmid clones. The RAPD clones are polymorphic fragments, potentially diagnostic for the various chromosomal forms of A. gamhar that are currently being analyzed.
Evolution of Anthocyanin Biosynthesis in Maize Kernels: The Role of Regulatory and Enzymatic Loci
Authors: Hanson Michael A , Gaut Brandon S , Stec Adrian O , Fuerstenberg Susan I , Goodman Major M , Coe Edward H , Doebley John F 
Published: January 2021

Abstract
Understanding which genes contribute to evolutionary change and the nature of the alterations in them are fundamental challenges in evolution. We analyzed regulatory and enzymatic genes in the maize anthocyanin pathway as related to the evolution of anthocyanin-pigmented kernels in maize from colorless kernels of its progenitor, teosinte. Genetic tests indicate that teosinte possesses functional alleles at all enzymatic loci. At two regulatory loci, most teosintes possess alleles that encode functional proteins, but ones that are not expressed during kernel development and not capable of activating anthocyanin biosynthesis there. We investigated nucleotide polymorphism at one of the regulatory loci, c1. Several observations suggest that c1 has not evolved in a strictly neutral manner, including an exceptionally low level of polymorphism and a biased representation of haplotypes in maize. Curiously, sequence data show that most of our teosinte samples possess a promoter element necessary for the activation of the anthocyanin pathway during kernel development, although genetic tests indicate that teosinte c1 alleles are not active during kernel development. Our analyses suggest that the evolution of the purple kernels resulted from changes in cis regulatory elements at regulatory loci and not changes in either regulatory protein function nor the enzymatic loci.
Realized Sampling Variances of Estimates of Genetic Parameters and the Difference Between Genetic and Phenotypic Correlations
Authors: Koots Kenneth R , Gibson John P 
Published: January 2021

Abstract
A data set of 1572 heritability estimates and 1015 pairs of genetic and phenotypic correlation estimates, constructed from a survey of published beef cattle genetic parameter estimates, provided a rare opportunity to study realized sampling variances of genetic parameter estimates. The distribution of both heritability estimates and genetic correlation estimates, when plotted against estimated accuracy, was consistent with random error variance being some three times the sampling variance predicted from standard formulae. This result was consistent with the observation that the variance of estimates of heritabilities and genetic correlations between populations were about four times the predicted sampling variance, suggesting few real differences in genetic parameters between populations. Except where there was a strong biological or statistical expectation of a difference, there was little evidence for differences between genetic and phenotypic correlations for most trait combinations or for differences in genetic correlations between populations. These results suggest that, even for controlled populations, estimating genetic parameters specific to a given population is less useful than commonly believed. A serendipitous discovery was that, in the standard formula for theoretical standard error of a genetic correlation estimate, the heritabilities refer to the estimated values and not, as seems generally assumed, the true population values.
Design III With Marker Loci
Authors: Cockerham C Clark , Zeng Zhao-Bang 
Published: January 2021

Abstract
Design III is an experimental design originally proposed by R. E. Comstock and H. F. Robinson for estimating genetic variances and the average degree of dominance for quantitative trait loci (QTL) and has recently been extended for mapping QTL. In this paper, we first extend Comstock and Robinson's analysis of variance to include linkage, two-locus epistasis and the use of F 3 parents. Then we develop the theory and statistical analysis of orthogonal contrasts and contrast × environment interaction for a single marker locus to characterize the effects of QTL. The methods are applied to the maize data of C. W. Stuber. The analyses strongly suggest that there are multiple linked QTL in many chromosomes for several traits examined. QTL effects are largely environment-independent for grain yield, ear height, plant height and ear leaf area and largely environment dependent for days to tassel, grain moisture and ear number. There is significant QTL epistasis. The results are generally in favor of the hypothesis of dominance of favorable genes to explain the observed heterosis in grain yield and other traits, although epistasis could also play an important role and overdominance at individual QTL level can not be ruled out.
The Amount of DNA Polymorphism Maintained in a Finite Population When the Neutral Mutation Rate Varies Among Sites
Authors: Tajima Fumio 
Published: January 2021

Abstract
The expectations of the average number of nucleotide differences per site (π), the proportion of segregating site (s), the minimum number of mutations per site (s*) and some other quantities were derived under the finite site models with and without rate variation among sites, where the finite site models include Jukes and Cantor's model, the equal-input model and Kimura's model. As a model of rate variation, the gamma distribution was used. The results indicate that if distribution parameter α is small, the effect of rate variation on these quantities are substantial, so that the estimates of θ based on the infinite site model are substantially underestimated, where θ = 4Nv, N is the effective population size and vis the mutation rate per site per generation. New methods for estimating θ are also presented, which are based on the finite site models with and without rate variation. Using these methods, underestimation can be corrected.
gutfeeling, a Drosophila Gene Encoding an Antizyme-Like Protein, Is Required for Late Differentiation of Neurons and Muscles
Authors: Salzberg Adi , Golden Krista , Bodmer Rolf , Bellen Hugo J 
Published: January 2021

Abstract
The gutfeeling (guf) gene was uncovered in a genetic screen for genes that are required for proper development of the embryonic peripheral nervous system. Mutations in guf cause defects in growth cone guidance and fasciculation and loss of expression of several neuronal markers in the embryonic peripheral and central nervous systems. guf is required for terminal differentiation of neuronal cells. Mutations in guf also affect the development of muscles in the embryo. In the absence of guf activity, myoblasts are formed properly, but myoblast fusion and further differentiation of muscle fibers is severely impaired. The guf gene was cloned and found to encode a 21-kD protein with a significant sequence similarity to the mammalian ornithine decarboxylase antizyme (OAZ). In mammals, OAZ plays a key regulatory role in the polyamine biosynthetic pathway through its binding to, and inhibition of, ornithine decarboxylase (ODC), the first enzyme in the pathway. The elaborate regulation of ODC activity in mammals still lacks a defined developmental role and little is known about the involvement of polyamines in cellular differentiation. GUF is the first antizyme-like protein identified in invertebrates. We discuss its possible developmental roles in light of this homology.
Evolution of Mouse T-box Genes by Tandem Duplication and Cluster Dispersion
Authors: Agulnik Sergei I , Garvey Nancy , Hancock Sarah , Ruvinsky Ilya , Chapman Deborah L , Agulnik Irina , Bollag Roni , Papaioannou Virginia , Silver Lee M 
Published: January 2021

Abstract
The T-box genes comprise an ancient family of putative transcription factors conserved across species as divergent as Mus musculus and Caenorhabditis elegans. All T-box gene products are characterized by a novel 174-186amino acid DNA binding domain called the T-box that was first discovered in the polypeptide products of the mouse T locus and the Drosophila melanogaster optomotor-blind gene. Earlier studies allowed the identification of five mouse T-box genes, T, Tbx1-3, and Tbr1, that all map to different chromosomal locations and are expressed in unique temporal and spatial patterns during embryogenesis. Here, we report the discovery of three new members of the mouse T-box gene family, named Tbx4, Tbx5, and Tbx6. Two of these newly discovered genes, Tbx4 and Tbx5, were found to be tightly linked to previously identified T-box genes. Combined results from phylogenetic, linkage, and physical mapping studies provide a picture for the evolution of a T-box subfamily by unequal crossing over to form a two-gene cluster that was duplicated and dispersed to two chromosomal locations. This analysis suggests that Tbx4 and Tbx5 are cognate genes that diverged apart from a common ancestral gene during early vertebrate evolution.
Opposite Orientations of an Inverted Duplication and Allelic Variation at the Mouse agouti Locus
Authors: Chen Yanru , Duhl David M J , Barsh Gregory S 
Published: January 2021

Abstract
The mouse agouti protein is a paracrine signaling molecule that causes yellow pigment synthesis. A pale ventral coloration distinguishes the light-bellied agouti (AW) from the agouti (A) allele, and is caused by expression of ventral-specific mRNA isoforms with a unique 5′ untranslated exon. Molecular cloning demonstrates this ventral-specific exon lies within a 3.1-kb element that is duplicated in the opposite orientation 15-kb upstream to produce an interrupted palindrome and that similarity between the duplicated elements has been maintained by gene conversion. Orientation of the palindrome is reversed in A compared to AW, which suggests that mutation from one allele to the other is caused by intrachromosomal homologous recombination mediated by sequences within the duplicated elements. Analysis of 15 inbred strains of laboratory and wild-derived mice with Southern hybridization probes and closely linked microsatellite markers suggests six haplotype groups: one typical for most strains that carry AW (129/SvJ, LP/J, CE/J, CAST/Ei), one typical for most strains that carry A (Balb/cJ, CBA/J, FVB/N, PERA/Rk, RBB/Dn); and four that are atypical (MOLC/Rk, MOLG/Dn, PERA/Ei, PERC/Ei, SPRET/Ei, RBA/Dn). Our results suggest a model for molecular evolution of the agouti locus in which homologous recombination can produce a reversible switch in allelic identity.
Mutation-Selection Balance at a Modifier-of-Imprinting Locus
Authors: Spencer Hamish G , Barnett Janine A 
Published: January 2021

Abstract
We propose a pair of population genetic models for a modifier-of-imprinting locus for which different genotypes imprint different proportions of an imprintable target locus in their gametes. The two models examine the situations in which imprinting is advantageous or disadvantageous, and we discuss three cases for which the modifier is respectively partially dominant, dominant, or recessive. The models predict the stable equilibrium frequencies of the mutant modifier and functionally diploid individuals in a large population in terms of up to four parameters: the mutation rate at the modifier locus, v; the selection coefficient against the disadvantageous phenotype, s; the proportion of unimprinted eggs produced by homozygotes for the mutant modifier, 8, and, in the partially dominant models, the dominance parameter, k. The equilibrium frequency of the mutant phenotypes is shown to be approximately twice that of standard Mendelian models: 2v/s or 4v/s when the modifier is recessive or dominant, respectively. Mathematical equivalences between these and nonimprinting models are noted.
Somatic Reversion of Chromosomal Position Effects in Drosophila melanogaster
Authors: Ahmad Kami , Golic Kent G 
Published: January 2021

Abstract
A transgene was inserted at several different chromosomal sites in Drosophila melanogaster, where its expression was subject to genomic position effects. Quantitative position effects and variegated and constant patterned position effects were observed. We investigated the status of the affected gene in the somatic cells where it normally functions. The FLP site-specific recombinase was used to remove the gene from the chromosome and its expression was then evaluated. We show that the FLP recombinase functions in cells that have finished their developmental program of mitoses. When FLP acts on directly repeated copies of its target site (FRT), the DNA flanked by those FRTs is excised from the chromosome as a closed circle. The extrachromosomal circle is maintained in nondividing cells, and a gene located on such a circle can be expressed. We then demonstrate that a gene subject to either variegated or constant position effect can be relieved of that effect by excision of the gene from the chromosome in cells where it would otherwise be inactive. We also observed a strong inhibition of FLP-mediated recombination for target sites located near centric heterochromatin.
Identification of the Sex-Determining Region of the Ceratitis capitata Y Chromosome by Deletion Mapping
Authors: Willhoeft Ute , Franz Gerald 
Published: January 2021

Abstract
In the medfly Ceratitis capitata, the Y chromosome is responsible for determining the male sex. We have mapped the region containing the relevant factor through the analysis of Y-autosome translocations using fluorescence in situ hybridization with two different probes. One probe, the clone pY114, contains repetitive, Y-specific DNA sequences from C. capitata, while the second clone, pDh2-H8, consists of ribosomal DNA sequences from Drosophila hydei. Clone pY114 labeled most of the long arm and pDh2-H8 hybridizes to the short arm and the centromeric region of the long arm. In 12 of the analyzed 19 Y-autosome translocation strains, adjacent-1 segregation products survive to the late pupal or even adult stage and can, therefore, be sexed. This was correlated with the length of the Y fragment still present in these aberrant individuals and allowed us to map the male-determining factor to a region of the long arm representing ~15% of the entire Y chromosome. No additional factors, affecting for example fertility, were detected outside the male-determining region.
Historical Selection, Amino Acid Polymorphism and Lineage-Specific Divergence at the G6pd Locus in Drosophila melanogaster and D. simulans
Authors: Eanes Walter F , Kirchner Michele , Yoon Jeanne , Biermann Christiane H , Wang Ing-Nang , McCartney Michael A , Verrelli Brian C 
Published: January 2021

Abstract
The nucleotide diversity across 1705 bp of the G6pd gene is studied in 50 Drosophila melanogaster and 12 D. simulans lines. Our earlier report contrasted intraspecific polymorphism and interspecific differences at silent and replacement sites in these species. This report expands the number of European and African lines and examines the pattern of polymorphism with respect to the common A/B allozymes. In D. melanogaster the silent nucleotide diversity varies 2.8-fold across localities. The B allele sequences are two- to fourfold more variable than the derived A allele, and differences between allozymes are twice as among B alleles. There is strong linkage disequilibrium across the G6pd region. In both species the level of silent polymorphism increases from the 5′ to 3′ ends, while there is no comparable pattern in level of silent site divergence or fixation. The neutral model is not rejected in either species. Using D. yakuba as an outgroup, the D. melanogaster lineage shows a twofold greater rate of silent fixation, but less than half the rate of amino acid replacement. Lineage-specific differences in mutation fixation are inconsistent with neutral expectations and suggest the interaction of species-specific population size differences with both weakly advantageous and deleterious selection.
Synergy Between Trehalose and Hsp104 for Thermotolerance in Saccharomyces cerevisiae
Authors: Elliott Beth , Haltiwanger Robert S , Futcher Bruce 
Published: January 2021

Abstract
We isolated a mutant strain unable to acquire heat shock resistance in stationary phase. Two mutations contributed to this phenotype. One mutation was at the TPS2locus, which encodes trehalose-6phosphate phosphatase. The mutant fails to make trehalose and accumulates trehalose-6-phosphate. The other mutation was at the HSP104 locus. Gene disruptions showed that tps2 and hsp104 null mutants each produced moderate heat shock sensitivity in stationary phase cells. The two mutations were synergistic and the double mutant had little or no stationary phase-induced heat shock resistance. The same effect was seen in the tps1 (trehalose-6phosphate synthase) hsp104 double mutant, suggesting that the extreme heat shock sensitivity was due mainly to a lack of trehalose rather than to the presence of trehalose-6 phosphate. However, accumulation of trehalose-6-phosphate did cause some phenotypes in the tps2 mutant, such as temperature sensitivity for growth. Finally, we isolated a high copy number suppressor of the temperature sensitivity of tps2, which we call PMU1, which reduced the levels of trehalose-6-phosphate in tps2 mutants. The encoded protein has a region homologous to the active site of phosphomutases.
Genetic Variation of Major Histocompatibility Complex and Microsatellite Loci: A Comparison in Bighorn Sheep
Authors: Boyce Walter M , Hedrick Philip W , Muggli-Cockett Noelle E , Kalinowski Steven , Penedo Maria Cecilia T , Ramey Rob R 
Published: January 2021

Examining and comparing genetic variation for major histocompatibility complex (MHC) and microsatellite (MS) loci in the same individuals provides an opportunity to understand the forces influencing genetic variation. We examined five MHC and three MS loci in 235 bighorn sheep (Ovis canadensis) from 14 populations and found that both types of loci were highly variable and were in Hardy-Weinberg proportions. Mean F ST values for both markers were very similar and MHC and MS genetic variability was predominantly distributed within rather than among populations. However, analyses of genetic distances and tree topologies revealed different spatial patterns of variation for the two types of loci. Collectively, these results indicated that neutral forces substantially influenced MS and MHC variation, and they provided limited evidence for selection acting on the MHC.