bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coalescent-Based Association Mapping and Fine Mapping of Complex Trait Loci
Authors: Zöllner Sebastian , Pritchard Jonathan K 
Published: October 2004

AbstractWe outline a general coalescent framework for using genotype data in linkage disequilibrium-based mapping studies. Our approach unifies two main goals of gene mapping that have generally been treated separately in the past: detecting association (i.e., significance testing) and estimating the location of the causative variation. To tackle the problem, we separate the inference into two stages. First, we use Markov chain Monte Carlo to sample from the posterior distribution of coalescent genealogies of all the sampled chromosomes without regard to phenotype. Then, averaging across genealogies, we estimate the likelihood of the phenotype data under various models for mutation and penetrance at an unobserved disease locus. The essential signal that these models look for is that in the presence of disease susceptibility variants in a region, there is nonrandom clustering of the chromosomes on the tree according to phenotype. The extent of nonrandom clustering is captured by the likelihood and can be used to construct significance tests or Bayesian posterior distributions for location. A novelty of our framework is that it can naturally accommodate quantitative data. We describe applications of the method to simulated data and to data from a Mendelian locus (CFTR, responsible for cystic fibrosis) and from a proposed complex trait locus (calpain-10, implicated in type 2 diabetes).
The Bacillus subtilis sin Operon
Authors: Voigt Christopher A , Wolf Denise M , Arkin Adam P 
Published: October 2004

Abstract
The strategy of combining genes from a regulatory protein and its antagonist within the same operon, but controlling their activities differentially, can lead to diverse regulatory functions. This protein-antagonist motif is ubiquitous and present in evolutionarily unrelated regulatory pathways. Using the sin operon from the Bacillus subtilis sporulation pathway as a model system, we built a theoretical model, parameterized it using data from the literature, and used bifurcation analyses to determine the circuit functions it could encode. The model demonstrated that this motif can generate a bistable switch with tunable control over the switching threshold and the degree of population heterogeneity. Further, the model predicted that a small perturbation of a single critical parameter can bias this architecture into functioning like a graded response, a bistable switch, an oscillator, or a pulse generator. By mapping the parameters of the model to specific DNA regions and comparing the genomic sequences of Bacillus species, we showed that phylogenetic variation tends to occur in those regions that tune the switch threshold without disturbing the circuit function. The dynamical plasticity of the protein-antagonist operon motif suggests that it is an evolutionarily convergent design selected not only for particular immediate function but also for its evolvability.
Epistasis Underlying a Fitness Trait Within a Natural Population of the Pitcher-Plant Mosquito, Wyeomyia smithii
Authors: Bradshaw William E , Haggerty Brian P , Holzapfel Christina M 
Published: October 2004

Abstract
We selected on divergent photoperiodic response in three separate lines from a natural population of the pitcher-plant mosquito, Wyeomyia smithii. Line crosses reveal that there exists within a population, diverse epistatic variation for a fitness trait that could contribute to adaptive potential following founder events or rapid climate change.
Communication Between Parental and Developing Genomes During Tetrahymena Nuclear Differentiation Is Likely Mediated by Homologous RNAs
Authors: Chalker Douglas L , Fuller Patrick , Yao Meng-Chao 
Published: October 2004

Abstract
Approximately 6000 DNA elements, totaling nearly 15 Mb, are coordinately excised from the developing somatic genome of Tetrahymena thermophila. An RNA interference (RNAi)-related mechanism has been implicated in the targeting of these germline-limited sequences for chromatin modification and subsequent DNA rearrangement. The excision of individual DNA segments can be inhibited if the homologous sequence is placed within the parental somatic nucleus, indicating that communication occurs between the parental and developing genomes. To determine how the DNA content of one nucleus is communicated to the other, we assessed DNA rearrangement occurring in wild-type cells that were mated to cells that contained the normally germline-limited M element within their somatic nuclei. M-element rearrangement was blocked in the wild-type cell even when no genetic exchange occurred between mating partners, a finding that is inconsistent with any genetic imprinting models. This inhibition by the parental somatic nucleus was rapidly established between 5 and 6 hr of conjugation, near or shortly after the time that zygotic nuclei are formed. M-element small RNAs (sRNAs) that are believed to direct its rearrangement were found to rapidly accumulate during the first few hours of conjugation before stabilizing to a low, steady-state level. The period between 5 and 6 hr during which sRNA levels stabilize correlates with the time after which the parental genome can block DNA rearrangement. These data lead us to suggest that homologous sRNAs serve as mediators to communicate sequence-specific information between the parental and developing genomes, thereby regulating genome-wide DNA rearrangement, and that these sRNAs can be effectively compared to the somatic genome of both parents.
A Novel Meiotic Drive Locus Almost Completely Distorts Segregation in Mimulus (Monkeyflower) Hybrids
Authors: Fishman Lila , Willis John H 
Published: October 2004

Abstract
We report the discovery, mapping, and characterization of a meiotic drive locus (D) exhibiting nearly 100% nonrandom transmission in hybrids between two species of yellow monkeyflowers, outcrossing Mimulus guttatus and selfing M. nasutus. Only 1% of F2 hybrids were M. nasutus homozygotes at the marker most tightly linked to D. We used a set of reciprocal backcrosses to distinguish among male-specific, female-specific, and zygote-specific sources of transmission ratio distortion. Transmission was severely distorted only when the heterozygous F1 acted as the female parent in crosses to either parental species, ruling out pollen competition and zygote mortality as potential sources of drive. After four generations of backcrossing to M. nasutus, nearly isogenic lines were still &gt;90% heterozygous at markers linked to D, suggesting that heterozygosity at the drive locus alone is sufficient for nonrandom transmission. A lack of dramatic female fitness costs in these lines rules out alternatives involving ovule or seed mortality and points to a truly meiotic mechanism of drive. The strength and direction of drive in this system is consistent with population genetic theory of selfish element evolution under different mating systems. These results are the first empirical demonstration of the strong female-specific drive predicted by new models of selfish centromere turnover.
Variation After a Selective Sweep in a Subdivided Population
Authors: Santiago Enrique , Caballero Armando 
Published: October 2004

Abstract
The effect of genetic hitchhiking on neutral variation is analyzed in subdivided populations with differentiated demes. After fixation of a favorable mutation, the consequences on particular subpopulations can be radically different. In the subpopulation where the mutation first appeared by mutation, variation at linked neutral loci is expected to be reduced, as predicted by the classical theory. However, the effect in the other subpopulations, where the mutation is introduced by migration, can be the opposite. This effect depends on the level of genetic differentiation of the subpopulations, the selective advantage of the mutation, the recombination frequency, and the population size, as stated by analytical derivations and computer simulations. The characteristic outcomes of the effect are three. First, the genomic region of reduced variation around the selected locus is smaller than that predicted in a panmictic population. Second, for more distant neutral loci, the amount of variation increases over the level they had before the hitchhiking event. Third, for these loci, the spectrum of gene frequencies is dominated by an excess of alleles at intermediate frequencies when compared with the neutral theory. At these loci, hitchhiking works like a system that takes variation from the between-subpopulation component and introduces it into the subpopulations. The mechanism can also operate in other systems in which the genetic variation is distributed in clusters with limited exchange of variation, such as chromosome arrangements or genomic regions closely linked to targets of balancing selection.
Photoperiod Regulates Flower Meristem Development in Arabidopsis thaliana
Authors: Jeong Sangho , Clark Steven E 
Published: October 2004

AbstractPhotoperiod has been known to regulate flowering time in many plant species. In Arabidopsis, genes in the long day (LD) pathway detect photoperiod and promote flowering under LD. It was previously reported that clavata2 (clv2) mutants grown under short day (SD) conditions showed suppression of the flower meristem defects, namely the accumulation of stem cells and the resulting production of extra floral organs. Detailed analysis of this phenomenon presented here demonstrates that the suppression is a true photoperiodic response mediated by the inactivation of the LD pathway under SD. Inactivation of the LD pathway was sufficient to suppress the clv2 defects under LD, and activation of the LD pathway under SD conditions restored clv2 phenotypes. These results reveal a novel role of photoperiod in flower meristem development in Arabidopsis. Flower meristem defects of clv1 and clv3 mutants are also suppressed under SD, and 35S:CO enhanced the defects of clv3, indicating that the LD pathway works independently from the CLV genes. A model is proposed to explain the interactions between photoperiod and the CLV genes.
Functional Evolution of the Vertebrate Myb Gene Family
Authors: Davidson Colin J , Tirouvanziam Rabindra , Herzenberg Leonard A , Lipsick Joseph S 
Published: October 2004

Abstract
The duplication of genes and genomes is believed to be a major force in the evolution of eukaryotic organisms. However, different models have been presented about how duplicated genes are preserved from elimination by purifying selection. Preservation of one of the gene copies due to rare mutational events that result in a new gene function (neofunctionalization) necessitates that the other gene copy retain its ancestral function. Alternatively, preservation of both gene copies due to rapid divergence of coding and noncoding regions such that neither retains the complete function of the ancestral gene (subfunctionalization) may result in a requirement for both gene copies for organismal survival. The duplication and divergence of the tandemly arrayed homeotic clusters have been studied in considerable detail and have provided evidence in support of the subfunctionalization model. However, the vast majority of duplicated genes are not clustered tandemly, but instead are dispersed in syntenic regions on different chromosomes, most likely as a result of genome-wide duplications and rearrangements. The Myb oncogene family provides an interesting opportunity to study a dispersed multigene family because invertebrates possess a single Myb gene, whereas all vertebrate genomes examined thus far contain three different Myb genes (A-Myb, B-Myb, and c-Myb). A-Myb and c-Myb appear to have arisen by a second round of gene duplication, which was preceded by the acquisition of a transcriptional activation domain in the ancestral A-Myb/c-Myb gene generated from the initial duplication of an ancestral B-Myb-like gene. B-Myb appears to be essential in all dividing cells, whereas A-Myb and c-Myb display tissue-specific requirements during spermatogenesis and hematopoiesis, respectively. We now report that the absence of Drosophila Myb (Dm-Myb) causes a failure of larval hemocyte proliferation and lymph gland development, while Dm-Myb−/− hemocytes from mosaic larvae reveal a phagocytosis defect. In addition, we show that vertebrate B-Myb, but neither vertebrate A-Myb nor c-Myb, can complement these hemocyte proliferation defects in Drosophila. Indeed, vertebrate A-Myb and c-Myb cause lethality in the presence or absence of endogenous Dm-Myb. These results are consistent with a neomorphic origin of an ancestral A-Myb/c-Myb gene from a duplicated B-Myb-like gene. In addition, our results suggest that B-Myb and Dm-Myb share essential conserved functions that are required for cell proliferation. Finally, these experiments demonstrate the utility of genetic complementation in Drosophila to explore the functional evolution of duplicated genes in vertebrates.
Satellite DNA From the Y Chromosome of the Malaria Vector Anopheles gambiaeSequence data from this article have been deposited with the EMBL/GenBank Data Libraries under accession nos. AY754141, AY754312.
Authors: Krzywinski Jaroslaw , Sangaré Djibril , Besansky Nora J 
Published: October 2004

AbstractSatellite DNA is an enigmatic component of genomic DNA with unclear function that has been regarded as “junk.” Yet, persistence of these tandem highly repetitive sequences in heterochromatic regions of most eukaryotic chromosomes attests to their importance in the genome. We explored the Anopheles gambiae genome for the presence of satellite repeats and identified 12 novel satellite DNA families. Certain families were found in close juxtaposition within the genome. Six satellites, falling into two evolutionarily linked groups, were investigated in detail. Four of them were experimentally confirmed to be linked to the Y chromosome, whereas their relatives occupy centromeric regions of either the X chromosome or the autosomes. A complex evolutionary pattern was revealed among the AgY477-like satellites, suggesting their rapid turnover in the A. gambiae complex and, potentially, recombination between sex chromosomes. The substitution pattern suggested rolling circle replication as an array expansion mechanism in the Y-linked 53-bp satellite families. Despite residing in different portions of the genome, the 53-bp satellites share the same monomer lengths, apparently maintained by molecular drive or structural constraints. Potential functional centromeric DNA structures, consisting of twofold dyad symmetries flanked by a common sequence motif, have been identified in both satellite groups.
Swi5 Acts in Meiotic DNA Joint Molecule Formation in Schizosaccharomyces pombe
Authors: Ellermeier Chad , Schmidt Henning , Smith Gerald R 
Published: October 2004

Abstract
Previously isolated Schizosaccharomyces pombe swi5 mutants are defective in mitotic mating-type switching and in repair of meiotic recombination-related DNA double-strand breaks. Here, we identify the swi5 gene, which encodes an 85-amino-acid polypeptide, similar to Sae3 of Saccharomyces cerevisiae, with an N-terminal predicted coiled-coil domain. A swi5 complete deletion mutant had normal mitotic growth rate but was hypersensitive to DNA-damaging agents and defective in mating-type switching. In meiosis, recombinant frequencies were reduced by a factor of ∼10. The swi5 deletion strongly reduced the viable spore yields of mutants lacking Rhp55 or Rhp57, proteins thought to aid joint molecule formation. Furthermore, the swi5 deletion strongly suppressed the low viable spore yield of mutants lacking Mus81•Eme1, which resolves joint molecules such as Holliday junctions. These and previous results indicate that the small Swi5 polypeptide acts in a branched pathway of joint molecule formation to repair meiotic DNA breaks.
Nucleotide Polymorphism and Linkage Disequilibrium Within and Among Natural Populations of European Aspen (Populus tremula L., Salicaceae)
Authors: Ingvarsson Pär K 
Published: October 2004

Abstract
Populus is an important model organism in forest biology, but levels of nucleotide polymorphisms and linkage disequilibrium have never been investigated in natural populations. Here I present a study on levels of nucleotide polymorphism, haplotype structure, and population subdivision in five nuclear genes in the European aspen Populus tremula. Results show substantial levels of genetic variation. Levels of silent site polymorphisms, πs, averaged 0.016 across the five genes. Linkage disequilibrium was generally low, extending only a few hundred base pairs, suggesting that rates of recombination are high in this obligate outcrossing species. Significant genetic differentiation was found at all five genes, with an average estimate of FST = 0.116. Levels of polymorphism in P. tremula are 2- to 10-fold higher than those in other woody, long-lived perennial plants, such as Pinus and Cryptomeria. The high levels of nucleotide polymorphism and low linkage disequilibrium suggest that it may be possible to map functional variation to very fine scales in P. tremula using association-mapping approaches.
A Torrid Zone on Mouse Chromosome 1 Containing a Cluster of Recombinational Hotspots
Authors: Kelmenson Peter M , Petkov Petko , Wang Xiaosong , Higgins David C , Paigen Beverly J , Paigen Kenneth 
Published: October 2004

Abstract
Within the 2.38-Mb Ath1 region of mouse chromosome 1, 42 of 45 genetic crossovers from crosses between C57BL/6J (B6) and either C3H/HeJ (H) or Mus spretus (SPRET) occurred in four zones (A–D); zone A, 100 kb long, contained a cluster of at least four recombination hotspots. F1 sperm assays indicate that within this “torrid zone” the most active hotspot (A3) can initiate recombination on H and SPRET but not B6 chromosomes. The A3 DNA sequence contains a (G/C)TTT repeat, long stretches of A or T, and a cyclic variation in AT content. Recombination was drastically reduced in a cross between B6 and a B6.SPRET Ath1 congenic strain, but was unaffected in a B6 × B6.H Ath1 congenic cross. Similar nonrandom clustering of hotspots has been observed in yeast and the major histocompatibility complexes of human and mouse. To the extent that torrid zones are a general feature of mammalian genomes, they have considerable implications for genetic mapping strategies in both human populations and mouse crosses.
MuDR Transposase Increases the Frequency of Meiotic Crossovers in the Vicinity of a Mu Insertion in the Maize a1 Gene
Authors: Yandeau-Nelson Marna D , Zhou Qing , Yao Hong , Xu Xiaojie , Nikolau Basil J , Schnable Patrick S 
Published: October 2004

AbstractAlthough DNA breaks stimulate mitotic recombination in plants, their effects on meiotic recombination are not known. Recombination across a maize a1 allele containing a nonautonomous Mu transposon was studied in the presence and absence of the MuDR-encoded transposase. Recombinant A1′ alleles isolated from a1-mum2/a1::rdt heterozygotes arose via either crossovers (32 CO events) or noncrossovers (8 NCO events). In the presence of MuDR, the rate of COs increased fourfold. This increase is most likely a consequence of the repair of MuDR-induced DNA breaks at the Mu1 insertion in a1-mum2. Hence, this study provides the first in vivo evidence that DNA breaks stimulate meiotic crossovers in plants. The distribution of recombination breakpoints is not affected by the presence of MuDR in that 19 of 24 breakpoints isolated from plants that carried MuDR mapped to a previously defined 377-bp recombination hotspot. This result is consistent with the hypothesis that the DNA breaks that initiate recombination at a1 cluster at its 5′ end. Conversion tracts associated with eight NCO events ranged in size from &lt;700 bp to &gt;1600 bp. This study also establishes that MuDR functions during meiosis and that ratios of CO/NCO vary among genes and can be influenced by genetic background.
The Generation of Cloned Drosophila melanogaster
Authors: Haigh Andrew J , MacDonald William A , Lloyd Vett K 
Published: October 2004

Abstract
We report here the first successful use of embryonic nuclear transfer to create viable adult Drosophila melanogaster clones. Given the generation time, cost effectiveness, and relative ease of embryonic nuclear transplant in Drosophila, this method can provide an opportunity to further study the constraints on development imposed by transplanting determined or differentiated nuclei.
Distinct Roles for the Saccharomyces cerevisiae Mismatch Repair Proteins in Heteroduplex Rejection, Mismatch Repair and Nonhomologous Tail Removal
Authors: Goldfarb Tamara , Alani Eric 
Published: October 2004

Abstract
The Saccharomyces cerevisiae mismatch repair (MMR) protein MSH6 and the SGS1 helicase were recently shown to play similarly important roles in preventing recombination between divergent DNA sequences in a single-strand annealing (SSA) assay. In contrast, MMR factors such as Mlh1p, Pms1p, and Exo1p were shown to not be required or to play only minimal roles. In this study we tested mutations that disrupt Sgs1p helicase activity, Msh2p-Msh6p mismatch recognition, and ATP binding and hydrolysis activities for their effect on preventing recombination between divergent DNA sequences (heteroduplex rejection) during SSA. The results support a model in which the Msh proteins act with Sgs1p to unwind DNA recombination intermediates containing mismatches. Importantly, msh2 mutants that displayed separation-of-function phenotypes with respect to nonhomologous tail removal during SSA and heteroduplex rejection were characterized. These studies suggest that nonhomologous tail removal is a separate function of Msh proteins that is likely to involve a distinct DNA binding activity. The involvement of Sgs1p in heteroduplex rejection but not nonhomologous tail removal further illustrates that subsets of MMR proteins collaborate with factors in different DNA repair pathways to maintain genome stability.
“Stress‐alleviating” and “vigilance‐enhancing” actions of Ginkgo biloba extract (EGb 761)
Authors: DeFeudis Francis V. , Drieu Katy 
Published: October 2004

AbstractThis overview is focused on the stress‐alleviating and vigilance‐enhancing properties of Ginkgo biloba extract (EGb 761) that have been observed in animal models and in humans and that appear useful in explaining the therapeutic effects of the extract on non‐cognitive brain functions that may be reflective of mood changes. With regard to its stress‐alleviating activity, in rodents EGb 761 facilitates behavioral adaptation, decreases circulating levels of corticosterone, catecholamines, ACTH, and CRH, suppresses the expression of the mitochondrial peripheral benzodiazepine receptor of the adrenal cortex, increases the anxiolytic activity of diazepam, increases arousal by an action that may involve GABAA receptor antagonism, induces anxiolytic‐like activity, prevents stress‐induced desensitization of hippocampal 5‐HT1A receptors, suppresses the down‐regulation of hippocampal glucocorticoid receptors, and facilitates decision‐making. In humans, EGb 761 has vigilance‐enhancing effects that support its clinical use in treating disorders involving stress‐induced brain dysfunction and those non‐cognitive symptoms of dementia currently classified as “behavioral and psychological symptoms of dementia” (BPSD). Collectively, these findings indicate that EGb 761 is useful for treating symptoms that are now classified as components of BPSD. As drug combinations consisting of EGb 761 and a non‐selective cholinesterase inhibitor, an antidepressant drug, or a neuroleptic could possibly be even more useful in treating BPSD, evaluation of such therapy is recommended. Drug Dev. Res. 62:1–25, 2004. © 2004 Wiley‐Liss, Inc.