bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Nonrandom Mating on Genetic Variance and Gene Flow in Populations With Mass Selection
Authors: Sánchez Leopoldo , Woolliams John A 
Published: August 2004

Abstract
The mechanisms by which nonrandom mating affects selected populations are not completely understood and remain a subject of scientific debate in the development of tractable predictors of population characteristics. The main objective of this study was to provide a predictive model for the genetic variance and covariance among mates for traits subjected to directional selection in populations with nonrandom mating based on the pedigree. Stochastic simulations were used to check the validity of this model. Our predictions indicate that the positive covariance among mates that is expected to result with preferential mating of relatives can be severely overpredicted from neutral expectations. The covariance expected from neutral theory is offset by an opposing covariance between the genetic mean of an individual's family and the Mendelian sampling term of its mate. This mechanism was able to predict the reduction in covariance among mates that we observed in the simulated populations and, in consequence, the equilibrium genetic variance and expected long-term genetic contributions. Additionally, this study provided confirmatory evidence on the postulated relationships of long-term genetic contributions with both the rate of genetic gain and the rate of inbreeding (ΔF) with nonrandom mating. The coefficient of variation of the expected gene flow among individuals and ΔF was sensitive to nonrandom mating when heritability was low, but less so as heritability increased, and the theory developed in the study was sufficient to explain this phenomenon.
The Yeast Splicing Factor Prp40p Contains Functional Leucine-Rich Nuclear Export Signals That Are Essential for Splicing
Authors: Murphy Mark W , Olson Brian L , Siliciano Paul G 
Published: August 2004

Abstract
To investigate the function of the essential U1 snRNP protein Prp40p, we performed a synthetic lethal screen in Saccharomyces cerevisiae. Using an allele of PRP40 that deletes 47 internal residues and causes only a slight growth defect, we identified aphenotypic mutations in three distinct complementation groups that conferred synthetic lethality. The synthetic phenotypes caused by these mutations were suppressed by wild-type copies of CRM1 (XPO1), YNL187w, and SME1, respectively. The strains whose synthetic phenotypes were suppressed by CRM1 contained no mutations in the CRM1 coding sequence or promoter. This indicates that overexpression of CRM1 confers dosage suppression of the synthetic lethality. Interestingly, PRP40 and YNL187w encode proteins with putative leucine-rich nuclear export signal (NES) sequences that fit the consensus sequence recognized by Crm1p. One of Prp40p's two NESs lies within the internal deletion. We demonstrate here that the NES sequences of Prp40p are functional for nuclear export in a leptomycin B-sensitive manner. Furthermore, mutation of these NES sequences confers temperature-sensitive growth and a pre-mRNA splicing defect. Although we do not expect that yeast snRNPs undergo compartmentalized biogenesis like their metazoan counterparts, our results suggest that Prp40p and Ynl187wp contain redundant NESs that aid in an important, Crm1p-mediated nuclear export event.
Estimating Effective Population Size or Mutation Rate With Microsatellites
Authors: Xu Hongyan , Fu Yun-Xin 
Published: August 2004

Abstract
Microsatellites are short tandem repeats that are widely dispersed among eukaryotic genomes. Many of them are highly polymorphic; they have been used widely in genetic studies. Statistical properties of all measures of genetic variation at microsatellites critically depend upon the composite parameter θ = 4Nμ, where N is the effective population size and μ is mutation rate per locus per generation. Since mutation leads to expansion or contraction of a repeat number in a stepwise fashion, the stepwise mutation model has been widely used to study the dynamics of these loci. We developed an estimator of θ, θ^F, on the basis of sample homozygosity under the single-step stepwise mutation model. The estimator is unbiased and is much more efficient than the variance-based estimator under the single-step stepwise mutation model. It also has smaller bias and mean square error (MSE) than the variance-based estimator when the mutation follows the multistep generalized stepwise mutation model. Compared with the maximum-likelihood estimator θ^L by Nielsen (1997), θ^F has less bias and smaller MSE in general. θ^L has a slight advantage when θ is small, but in such a situation the bias in θ^L may be more of a concern.
A Bivalent Polyploid Model for Mapping Quantitative Trait Loci in Outcrossing Tetraploids
Authors: Wu Rongling , Ma Chang-Xing , Casella George 
Published: August 2004

AbstractTwo major aspects have made the genetic and genomic study of polyploids extremely difficult. First, increased allelic or nonallelic combinations due to multiple alleles result in complex gene actions and interactions for quantitative trait loci (QTL) in polyploids. Second, meiotic configurations in polyploids undergo a complex biological process including either bivalent or multivalent formation, or both. For bivalent polyploids, different degrees of preferential chromosome pairings may occur during meiosis. In this article, we develop a maximum-likelihood-based model for mapping QTL in tetraploids by considering the quantitative inheritance and meiotic mechanism of bivalent polyploids. This bivalent polyploid model is implemented with the EM algorithm to simultaneously estimate QTL position, QTL effects, and QTL-marker linkage phases by incorporating the impact of a cytological parameter determining bivalent chromosome pairings (the preferential pairing factor). Simulation studies are performed to investigate the performance and robustness of our statistical method for parameter estimation. The implication and extension of the bivalent polyploid model are discussed.
Influence of Dominance, Leptokurtosis and Pleiotropy of Deleterious Mutations on Quantitative Genetic Variation at Mutation-Selection Balance
Authors: Zhang Xu-Sheng , Wang Jinliang , Hill William G 
Published: August 2004

Abstract
In models of maintenance of genetic variance (VG) it has often been assumed that mutant alleles act additively. However, experimental data show that the dominance coefficient varies among mutant alleles and those of large effect tend to be recessive. On the basis of empirical knowledge of mutations, a joint-effect model of pleiotropic and real stabilizing selection that includes dominance is constructed and analyzed. It is shown that dominance can dramatically alter the prediction of equilibrium VG. Analysis indicates that for the situations where mutations are more recessive for fitness than for a quantitative trait, as supported by the available data, the joint-effect model predicts a significantly higher VG than does an additive model. Importantly, for what seem to be realistic distributions of mutational effects (i.e., many mutants may not affect the quantitative trait substantially but are likely to affect fitness), the observed high levels of genetic variation in the quantitative trait under strong apparent stabilizing selection can be generated. This investigation supports the hypothesis that most VG comes from the alleles nearly neutral for fitness in heterozygotes while apparent stabilizing selection is contributed mainly by the alleles of large effect on the quantitative trait. Thus considerations of dominance coefficients of mutations lend further support to our previous conclusion that mutation-selection balance is a plausible mechanism of the maintenance of the genetic variance in natural populations.
Bayesian Estimation of Genomic Distance
Authors: Durrett Richard , Nielsen Rasmus , York Thomas L 
Published: August 2004

Abstract
We present a Bayesian approach to the problem of inferring the number of inversions and translocations separating two species. The main reason for developing this method is that it will allow us to test hypotheses about the underlying mechanisms, such as the distribution of inversion track lengths or rate constancy among lineages. Here, we apply these methods to comparative maps of eggplant and tomato, human and cat, and human and cattle with 170, 269, and 422 markers, respectively. In the first case the most likely number of events is larger than the parsimony value. In the last two cases the parsimony solutions have very small probability.
On the Metropolis-Hastings Acceptance Probability to Add or Drop a Quantitative Trait Locus in Markov Chain Monte Carlo-Based Bayesian Analyses
Authors: Jannink Jean-Luc , Fernando Rohan L 
Published: August 2004

Abstract
The Metropolis-Hastings algorithm used in analyses that estimate the number of QTL segregating in a mapping population requires the calculation of an acceptance probability to add or drop a QTL from the model. Expressions for this acceptance probability need to recognize that sets of QTL are unordered such that the number of equivalent sets increases with the factorial of the QTL number. Here, we show how accounting for this fact affects the acceptance probability and review expressions found in the literature.
Marker-Based Cloning of the Region Containing the UhAvr1 Avirulence Gene From the Basidiomycete Barley Pathogen Ustilago hordei
Authors: Linning R , Lin D , Lee N , Abdennadher M , Gaudet D , Thomas P , Mills D , Kronstad J W , Bakkeren G 
Published: August 2004

Abstract
Race-cultivar specialization during the interaction of the basidiomycete smut pathogen Ustilago hordei with its barley host was described in the 1940s. Subsequent genetic analyses revealed the presence of dominant avirulence genes in the pathogen that conform to the gene-for-gene theory. This pathosystem therefore presents an opportunity for the molecular genetic characterization of fungal genes controlling avirulence. We performed a cross between U. hordei strains to obtain 54 progeny segregating for three dominant avirulence genes on three differential barley cultivars. Bulked segregant analysis was used to identify RAPD and AFLP markers tightly linked to the avirulence gene UhAvr1. The UhAvr1 gene is located in an area containing repetitive DNA and this region is undetectable in cosmid libraries prepared from the avirulent parental strain. PCR and hybridization probes developed from the linked markers were therefore used to identify cosmid clones from the virulent (Uhavr1) parent. By walking on Uhavr1-linked cosmid clones, a nonrepetitive, nearby probe was found that recognized five overlapping BAC clones spanning 170 kb from the UhAvr1 parent. A contig of the clones in the UhAvr1 region was constructed and selected probes were used for RFLP analysis of the segregating population. This approach genetically defined an ∼80-kb region that carries the UhAvr1 gene and provided cloned sequences for subsequent genetic analysis. UhAvr1 represents the first avirulence gene cloned from a basidiomycete plant pathogen.
A dnaC Mutation in Escherichia coli That Affects Copy Number of ColE1-Like Plasmids and the PriA-PriB (but Not Rep-PriC)Pathway of Chromosomal Replication Restart
Authors: Harinarayanan R , Gowrishankar J 
Published: August 2004

Abstract
Escherichia coli nusG and rho mutants, which are defective in transcription termination, are killed following transformation with several ColE1-like plasmids that lack the plasmid-encoded copy-number regulator gene rom because of uncontrolled plasmid replication within the cells. In this study, a mutation [dna-C1331(A84T)] in the dnaC gene encoding the replicative helicase-loading protein was characterized as a suppressor of this plasmid-mediated lethality phenotype. The mutation also reduced the copy number of the plasmids in otherwise wild-type strains. In comparison with the isogenic dnaC+ strain, the dnaC mutant was largely unaffected for (i) growth on rich or minimal medium, (ii) tolerance to UV irradiation, or (iii) survival in the absence of the PriA, RecA, or RecB proteins. However, it was moderately SOS-induced and was absolutely dependent on both the Rep helicase and the PriC protein for its viability. A dnaC1331(A84T) dam mutant, but not its mutH derivative, exhibited sensitivity to growth on rich medium, suggestive of a reduced capacity in the dnaC1331(A84T) strains to survive chromosomal double-strand breaks. We propose that DnaC-A84T is proficient in the assembly of replication forks for both initiation of chromosome replication (at oriC) and replication restart via the Rep-PriC pathway, but that it is specifically defective for replication restart via the PriA-PriB pathway (and consequently also for replication of the Rom– ColE1-like plasmids).
The Identification of Pcl1-Interacting Proteins That Genetically Interact With Cla4 May Indicate a Link Between G1 Progression and Mitotic Exit
Authors: Keniry Megan E , Kemp Hilary A , Rivers David M , Sprague George F 
Published: August 2004

Abstract
In budding yeast, Cla4 and Ste20, two p21-activated kinases, contribute to numerous morphogenetic processes. Loss of Ste20 or Cla4 individually confers distinct phenotypes, implying that they regulate different processes. However, loss of both proteins is lethal, suggesting some functional overlap. To explore the role(s) of Cla4, we and others have sought mutations that are lethal in a cla4Δ strain. These mutations define &gt;60 genes. Recently, both Ste20 and Cla4 have been implicated in mitotic exit. Here, we identify a genetic interaction between PHO85, which encodes a cyclin-dependent kinase, and CLA4. We further show that the Pho85-coupled G1 cyclins Pcl1 and Pcl2 contribute to this Pho85 role. We performed a two-hybrid screen with Pcl1. Three Pcl1-interacting proteins were identified: Ncp1, Hms1, and a novel ATPase dubbed Epa1. Each of these proteins interacts with Pcl1 in GST pull-down experiments and is specifically phosphorylated by Pcl1•Pho85 complexes. NCP1, HMS1, and EPA1 also genetically interact with CLA4. Like Cla4, the proteins Hms1, Ncp1, and Pho85 appear to affect mitotic exit, a conclusion that follows from the mislocalization of Cdc14, a key mitotic regulator, in strains lacking these proteins. We propose a model in which the G1 Pcl1•Pho85 complex regulates mitotic exit machinery.
PaASK1, a Mitogen-Activated Protein Kinase Kinase Kinase That Controls Cell Degeneration and Cell Differentiation in Podospora anserina
Authors: Kicka Sébastien , Silar Philippe 
Published: August 2004

Abstract
MAPKKK are kinases involved in cell signaling. In fungi, these kinases are known to regulate development, pathogenicity, and the sensing of external conditions. We show here that Podospora anserina strains mutated in PaASK1, a MAPKKK of the MEK family, are impaired in the development of crippled growth, a cell degeneration process caused by C, a nonconventional infectious element. They also display defects in mycelium pigmentation, differentiation of aerial hyphae, and making of fruiting bodies, three hallmarks of cell differentiation during stationary phase in P. anserina. Overexpression of PaASK1 results in exacerbation of crippled growth. PaASK1 is a large protein of 1832 amino acids with several domains, including a region rich in proline and a 60-amino-acid-long polyglutamine stretch. Deletion analysis reveals that the polyglutamine stretch is dispensable for PaASK1 activity, whereas the region that contains the prolines is essential but insufficient to promote full activity. We discuss a model based on the hysteresis of a signal transduction cascade to account for the role of PaASK1 in both cell degeneration and stationary-phase cell differentiation.
Differential Effects of Drosophila Mastermind on Asymmetric Cell Fate Specification and Neuroblast Formation
Authors: Yedvobnick Barry , Kumar Anumeha , Chaudhury Padmashree , Opraseuth Jonathan , Mortimer Nathan , Bhat Krishna Moorthi 
Published: August 2004

Abstract
During neurogenesis in the ventral nerve cord of the Drosophila embryo, Notch signaling participates in the pathway that mediates asymmetric fate specification to daughters of secondary neuronal precursor cells. In the NB4-2 → GMC-1 → RP2/sib lineage, a well-studied neuronal lineage in the ventral nerve cord, Notch signaling specifies sib fate to one of the daughter cells of GMC-1. Notch mediates this process via Mastermind (Mam). Loss of function for mam, similar to loss of function for Notch, results in GMC-1 symmetrically dividing to generate two RP2 neurons. Loss of function for mam also results in a severe neurogenic phenotype. In this study, we have undertaken a functional analysis of the Mam protein. We show that while ectopic expression of a truncated Mam protein induces a dominant-negative neurogenic phenotype, it has no effect on asymmetric fate specification. This truncated Mam protein rescues the loss of asymmetric specification phenotype in mam in an allele-specific manner. We also show an interallelic complementation of loss-of-asymmetry defect. Our results suggest that Mam proteins might associate during the asymmetric specification of cell fates and that the N-terminal region of the protein plays a role in this process.
Evidence for a piwi-Dependent RNA Silencing of the gypsy Endogenous Retrovirus by the Drosophila melanogaster flamenco Gene
Authors: Sarot Emeline , Payen-Groschêne Geneviève , Bucheton Alain , Pélisson Alain 
Published: August 2004

Abstract
In Drosophila melanogaster, the endogenous retrovirus gypsy is repressed by the functional alleles (restrictive) of an as-yet-uncloned heterochromatic gene called flamenco. Using gypsy-lacZ transcriptional fusions, we show here that this repression takes place not only in the follicle cells of restrictive ovaries, as was previously observed, but also in restrictive larval female gonads. Analyses of the role of gypsy cis-regulatory sequences in the control of gypsy expression are also presented. They rule out the hypothesis that gypsy would contain a single binding region for a putative Flamenco repressor. Indeed, the ovarian expression of a chimeric yp3-lacZ construct was shown to become sensitive to the Flamenco regulation when any of three different 5′-UTR gypsy sequences (ranging from 59 to 647 nucleotides) was incorporated into the heterologous yp3-lacZ transcript. The piwi mutation, which is known to affect RNA-mediated homology-dependent transgene silencing, was also shown to impede the repression of gypsy in restrictive female gonads. Finally, a RNA-silencing model is also supported by the finding in ovaries of short RNAs (25–27 nucleotides long) homologous to sequences from within the gypsy 5′-UTR.
Linkage Disequilibrium in the Domesticated Pig
Authors: Nsengimana Jérémie , Baret Philippe , Haley Chris S , Visscher Peter M 
Published: August 2004

Abstract
This study investigated the extent of linkage disequilibrium (LD) in two genomic regions (on chromosomes 4 and 7) in five populations of domesticated pigs. LD was measured with D′ and tested for significance with the Fisher exact test. Effects of genetic (linkage) distance, chromosome, population, and their interactions on D′ were tested both through a linear model analysis of covariance and by a theoretical nonlinear model. The overall result was that (1) the distance explained most of the variability of D′, (2) the effect of chromosome was significant, and (3) the effect of population was significant. The significance of the chromosome effect may have resulted from selection and the significance of the population effect illustrates the effects of population structures and effective population sizes on LD. These results suggest that mapping methods based on LD may be valuable even with only moderately dense marker spacing in pigs.
Functional Divergence in Tandemly Duplicated Arabidopsis thaliana Trypsin Inhibitor Genes
Authors: Clauss M J , Mitchell-Olds T 
Published: August 2004

Abstract
In multigene families, variation among loci and alleles can contribute to trait evolution. We explored patterns of functional and genetic variation in six duplicated Arabidopsis thaliana trypsin inhibitor (ATTI) loci. We demonstrate significant variation in constitutive and herbivore-induced transcription among ATTI loci that show, on average, 65% sequence divergence. Significant variation in ATTI expression was also found between two molecularly defined haplotype classes. Population genetic analyses for 17 accessions of A. thaliana showed that six ATTI loci arranged in tandem within 10 kb varied 10-fold in nucleotide diversity, from 0.0009 to 0.0110, and identified a minimum of six recombination events throughout the tandem array. We observed a significant peak in nucleotide and indel polymorphism spanning ATTI loci in the interior of the array, due primarily to divergence between the two haplotype classes. Significant deviation from the neutral equilibrium model for individual genes was interpreted within the context of intergene linkage disequilibrium and correlated patterns of functional differentiation. In contrast to the outcrosser Arabidopsis lyrata for which recombination is observed even within ATTI loci, our data suggest that response to selection was slowed in the inbreeding, annual A. thaliana because of interference among functionally divergent ATTI loci.
Multiple Loci and Epistases Control Genetic Variation for Seed Dormancy in Weedy Rice (Oryza sativa)
Authors: Gu Xing-You , Kianian Shahryar F , Foley Michael E 
Published: August 2004

Abstract
Weedy rice has much stronger seed dormancy than cultivated rice. A wild-like weedy strain SS18-2 was selected to investigate the genetic architecture underlying seed dormancy, a critical adaptive trait in plants. A framework genetic map covering the rice genome was constructed on the basis of 156 BC1 [EM93-1 (nondormant breeding line)//EM93-1/SS18-2] individuals. The mapping population was replicated using a split-tiller technique to control and better estimate the environmental variation. Dormancy was determined by germination of seeds after 1, 11, and 21 days of after-ripening (DAR). Six dormancy QTL, designated as qSDS-4, -6, -7-1, -7-2, -8, and -12, were identified. The locus qSDS-7-1 was tightly linked to the red pericarp color gene Rc. A QTL × DAR interaction was detected for qSDS-12, the locus with the largest main effect at 1, 11, and 21 DAR (R2 = 0.14, 0.24, and 0.20, respectively). Two, three, and four orders of epistases were detected with four, six, and six QTL, respectively. The higher-order epistases strongly suggest the presence of genetically complex networks in the regulation of variation for seed dormancy in natural populations and make it critical to select for a favorable combination of alleles at multiple loci in positional cloning of a target dormancy gene.
Stochastic Tunnels in Evolutionary Dynamics
Authors: Iwasa Yoh , Michor Franziska , Nowak Martin A 
Published: August 2004

Abstract
We study a situation that arises in the somatic evolution of cancer. Consider a finite population of replicating cells and a sequence of mutations: type 0 can mutate to type 1, which can mutate to type 2. There is no back mutation. We start with a homogeneous population of type 0. Mutants of type 1 emerge and either become extinct or reach fixation. In both cases, they can generate type 2, which also can become extinct or reach fixation. If mutation rates are small compared to the inverse of the population size, then the stochastic dynamics can be described by transitions between homogeneous populations. A “stochastic tunnel” arises, when the population moves from all 0 to all 2 without ever being all 1. We calculate the exact rate of stochastic tunneling for the case when type 1 is as fit as type 0 or less fit. Type 2 has the highest fitness. We discuss implications for the elimination of tumor suppressor genes and the activation of genetic instability. Although our theory is developed for cancer genetics, stochastic tunnels are general phenomena that could arise in many circumstances.