bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating Diversifying Selection and Functional Constraint in the Presence of Recombination
Authors: Wilson Daniel J , McVean Gilean 
Published: December 2005

Abstract
Models of molecular evolution that incorporate the ratio of nonsynonymous to synonymous polymorphism (dN/dS ratio) as a parameter can be used to identify sites that are under diversifying selection or functional constraint in a sample of gene sequences. However, when there has been recombination in the evolutionary history of the sequences, reconstructing a single phylogenetic tree is not appropriate, and inference based on a single tree can give misleading results. In the presence of high levels of recombination, the identification of sites experiencing diversifying selection can suffer from a false-positive rate as high as 90%. We present a model that uses a population genetics approximation to the coalescent with recombination and use reversible-jump MCMC to perform Bayesian inference on both the dN/dS ratio and the recombination rate, allowing each to vary along the sequence. We demonstrate that the method has the power to detect variation in the dN/dS ratio and the recombination rate and does not suffer from a high false-positive rate. We use the method to analyze the porB gene of Neisseria meningitidis and verify the inferences using prior sensitivity analysis and model criticism techniques.
Identification of Drosophila Genes Modulating Janus Kinase/Signal Transducer and Activator of Transcription Signal Transduction
Authors: Mukherjee Tina , Schäfer Ulrich , Zeidler Martin P 
Published: December 2005

Abstract
The JAK/STAT pathway was first identified in mammals as a signaling mechanism central to hematopoiesis and has since been shown to exert a wide range of pleiotropic effects on multiple developmental processes. Its inappropriate activation is also implicated in the development of numerous human malignancies, especially those derived from hematopoietic lineages. The JAK/STAT signaling cascade has been conserved through evolution and although the pathway identified in Drosophila has been closely examined, the full complement of genes required to correctly transduce signaling in vivo remains to be identified. We have used a dosage-sensitive dominant eye overgrowth phenotype caused by ectopic activation of the JAK/STAT pathway to screen 2267 independent, newly generated mutagenic P-element insertions. After multiple rounds of retesting, 23 interacting loci that represent genes not previously known to interact with JAK/STAT signaling have been identified. Analysis of these genes has identified three signal transduction pathways, seven potential components of the pathway itself, and six putative downstream pathway target genes. The use of forward genetics to identify loci and reverse genetic approaches to characterize them has allowed us to assemble a collection of genes whose products represent novel components and regulators of this important signal transduction cascade.
DNA Sequence Variation and Selection of Tag Single-Nucleotide Polymorphisms at Candidate Genes for Drought-Stress Response in Pinus taeda L.
Authors: González-Martínez Santiago C , Ersoz Elhan , Brown Garth R , Wheeler Nicholas C , Neale David B 
Published: December 2005

Abstract
Genetic association studies are rapidly becoming the experimental approach of choice to dissect complex traits, including tolerance to drought stress, which is the most common cause of mortality and yield losses in forest trees. Optimization of association mapping requires knowledge of the patterns of nucleotide diversity and linkage disequilibrium and the selection of suitable polymorphisms for genotyping. Moreover, standard neutrality tests applied to DNA sequence variation data can be used to select candidate genes or amino acid sites that are putatively under selection for association mapping. In this article, we study the pattern of polymorphism of 18 candidate genes for drought-stress response in Pinus taeda L., an important tree crop. Data analyses based on a set of 21 putatively neutral nuclear microsatellites did not show population genetic structure or genomewide departures from neutrality. Candidate genes had moderate average nucleotide diversity at silent sites (πsil = 0.00853), varying 100-fold among single genes. The level of within-gene LD was low, with an average pairwise r2 of 0.30, decaying rapidly from ∼0.50 to ∼0.20 at 800 bp. No apparent LD among genes was found. A selective sweep may have occurred at the early-response-to-drought-3 (erd3) gene, although population expansion can also explain our results and evidence for selection was not conclusive. One other gene, ccoaomt-1, a methylating enzyme involved in lignification, showed dimorphism (i.e., two highly divergent haplotype lineages at equal frequency), which is commonly associated with the long-term action of balancing selection. Finally, a set of haplotype-tagging SNPs (htSNPs) was selected. Using htSNPs, a reduction of genotyping effort of ∼30–40%, while sampling most common allelic variants, can be gained in our ongoing association studies for drought tolerance in pine.
Phylogeographic History and Gene Flow Among Giant Galápagos Tortoises on Southern Isabela Island
Authors: Ciofi Claudio , Wilson Gregory A , Beheregaray Luciano B , Marquez Cruz , Gibbs James P , Tapia Washington , Snell Howard L , Caccone Adalgisa , Powell Jeffrey R 
Published: December 2005

AbstractVolcanic islands represent excellent models with which to study the effect of vicariance on colonization and dispersal, particularly when the evolution of genetic diversity mirrors the sequence of geological events that led to island formation. Phylogeographic inference, however, can be particularly challenging for recent dispersal events within islands, where the antagonistic effects of land bridge formation and vicariance can affect movements of organisms with limited dispersal ability. We investigated levels of genetic divergence and recovered signatures of dispersal events for 631 Galápagos giant tortoises across the volcanoes of Sierra Negra and Cerro Azul on the island of Isabela. These volcanoes are among the most recent formations in the Galápagos (&lt;0.7 million years), and previous studies based on genetic and morphological data could not recover a consistent pattern of lineage sorting. We integrated nested clade analysis of mitochondrial DNA control region sequences, to infer historical patterns of colonization, and a novel Bayesian multilocus genotyping method for recovering evidence of recent migration across volcanoes using eleven microsatellite loci. These genetic studies illuminate taxonomic distinctions as well as provide guidance to possible repatriation programs aimed at countering the rapid population declines of these spectacular animals.
The Power of Single-Nucleotide Polymorphisms for Large-Scale Parentage Inference
Authors: Anderson Eric C , Garza John Carlos 
Published: December 2005

Abstract
Likelihood-based parentage inference depends on the distribution of a likelihood-ratio statistic, which, in most cases of interest, cannot be exactly determined, but only approximated by Monte Carlo simulation. We provide importance-sampling algorithms for efficiently approximating very small tail probabilities in the distribution of the likelihood-ratio statistic. These importance-sampling methods allow the estimation of small false-positive rates and hence permit likelihood-based inference of parentage in large studies involving a great number of potential parents and many potential offspring. We investigate the performance of these importance-sampling algorithms in the context of parentage inference using single-nucleotide polymorphism (SNP) data and find that they may accelerate the computation of tail probabilities &gt;1 millionfold. We subsequently use the importance-sampling algorithms to calculate the power available with SNPs for large-scale parentage studies, paying particular attention to the effect of genotyping errors and the occurrence of related individuals among the members of the putative mother–father–offspring trios. These simulations show that 60–100 SNPs may allow accurate pedigree reconstruction, even in situations involving thousands of potential mothers, fathers, and offspring. In addition, we compare the power of exclusion-based parentage inference to that of the likelihood-based method. Likelihood-based inference is much more powerful under many conditions; exclusion-based inference would require 40% more SNP loci to achieve the same accuracy as the likelihood-based approach in one common scenario. Our results demonstrate that SNPs are a powerful tool for parentage inference in large managed and/or natural populations.
Molecular Evolution in the Drosophila melanogaster Species Subgroup: Frequent Parameter Fluctuations on the Timescale of Molecular Divergence
Authors: Akashi Hiroshi , Ko Wen-Ya , Piao Shengfu , John Anoop , Goel Piyush , Lin Chiao-Feng , Vitins Alexa P 
Published: December 2005

Abstract
Although mutation, genetic drift, and natural selection are well established as determinants of genome evolution, the importance (frequency and magnitude) of parameter fluctuations in molecular evolution is less understood. DNA sequence comparisons among closely related species allow specific substitutions to be assigned to lineages on a phylogenetic tree. In this study, we compare patterns of codon usage and protein evolution in 22 genes (&gt;11,000 codons) among Drosophila melanogaster and five relatives within the D. melanogaster subgroup. We assign changes to eight lineages using a maximum-likelihood approach to infer ancestral states. Uncertainty in ancestral reconstructions is taken into account, at least to some extent, by weighting reconstructions by their posterior probabilities. Four of the eight lineages show potentially genomewide departures from equilibrium synonymous codon usage; three are decreasing and one is increasing in major codon usage. Several of these departures are consistent with lineage-specific changes in selection intensity (selection coefficients scaled to effective population size) at silent sites. Intron base composition and rates and patterns of protein evolution are also heterogeneous among these lineages. The magnitude of forces governing silent, intron, and protein evolution appears to have varied frequently, and in a lineage-specific manner, within the D. melanogaster subgroup.
Genetic Association Analysis of Human Longevity in Cohort Studies of Elderly Subjects: An Example of the PON1 Gene in the Danish 1905 Birth Cohort
Authors: Tan Qihua , Christiansen Lene , Bathum Lise , Li Shuxia , Kruse Torben A , Christensen Kaare 
Published: December 2005

Abstract
Although the case-control or the cross-sectional design has been popular in genetic association studies of human longevity, such a design is prone to false positive results due to sampling bias and a potential secular trend in gene–environment interactions. To avoid these problems, the cohort or follow-up study design has been recommended. With the observed individual survival information, the Cox regression model has been used for single-locus data analysis. In this article, we present a novel survival analysis model that combines population survival with individual genotype and phenotype information in assessing the genetic association with human longevity in cohort studies. By monitoring the changes in the observed genotype frequencies over the follow-up period in a birth cohort, we are able to assess the effects of the genotypes and/or haplotypes on individual survival. With the estimated parameters, genotype- and/or haplotype-specific survival and hazard functions can be calculated without any parametric assumption on the survival distribution. In addition, our model estimates haplotype frequencies in a birth cohort over the follow-up time, which is not observable in the multilocus genotype data. A computer simulation study was conducted to specifically assess the performance and power of our haplotype-based approach for given risk and frequency parameters under different sample sizes. Application of our method to paraoxonase 1 genotype data detected a haplotype that significantly reduces carriers' hazard of death and thus reveals and stresses the important role of genetic variation in maintaining human survival at advanced ages.
Cryptic Genetic Variation Is Enriched for Potential Adaptations
Authors: Masel Joanna 
Published: December 2005

AbstractCryptic genetic variation accumulates under weakened selection and has been proposed as a source of evolutionary innovations. Weakened selection may, however, also lead to the accumulation of strongly deleterious or lethal alleles, swamping the effect of any potentially adaptive alleles when they are revealed. Here I model variation that is partially shielded from selection, assuming that unconditionally deleterious variation is more strongly deleterious than variation that is potentially adaptive in a future environment. I find that cryptic genetic variation can be substantially enriched for potential adaptations under a broad range of realistic parameter values, including those applicable to alternative splices and readthrough products generated by the yeast prion [PSI+]. This enrichment is dramatically stronger when multiple simultaneous changes are required to generate a potentially adaptive phenotype. Cryptic genetic variation is likely to be an effective source of useful adaptations at a time of environmental change, relative to an equivalent source of variation that has not spent time in a hidden state.
Genomewide Comparative Analysis of the Highly Abundant Transposable Element DINE-1 Suggests a Recent Transpositional Burst in Drosophila yakuba
Authors: Yang Hsiao-Pei , Hung Tzu-Ling , You Tzung-Lin , Yang Tzung-Han 
Published: December 2005

Abstract
DINE-1 (Drosophila interspersed element) is the most abundant repetitive sequence in the Drosophila genome derived from transposable elements. It comprises &gt;1% of the Drosophila melanogaster genome (DMG) and is believed to be a relic from an ancient transpositional burst that occurred ∼5–10 MYA. We performed a genomewide comparison of the abundance, sequence variation, and chromosomal distribution of DINE-1 in D. melanogaster and D. yakuba. Unlike the highly diverged copies in the DMG (pairwise distance ∼15%), DINE-1's in the Drosophila yakuba genome (DYG) have diverged by only 3.4%. Moreover, the chromosomal distribution of DINE-1 in the two species is very different, with a significant number of euchromatic insertions found only in D. yakuba. We propose that these different patterns are caused by a second transpositional burst of DINE-1's in the D. yakuba genome ∼1.5 MYA. On the basis of the sequence of these recently transposed copies, we conclude that DINE-1 is likely to be a family of nonautomomous DNA transposons. Analysis of the chromosomal distribution of two age groups of DINE-1's in D. yakuba indicates that (1) there is a negative correlation between recombination rates and the density of DINE-1's and (2) younger copies are more evenly distributed in the chromosome arms, while older copies are mostly located near the centromere regions. Our results fit the predictions of a selection–transposition balance model. Our data on whole-genome comparison of a highly abundant TE among Drosophila sibling species demonstrate the unexpectedly dynamic nature of TE activity in different host genomes.
Organization of the sex-ratio Meiotic Drive Region in Drosophila simulans
Authors: Montchamp-Moreau Catherine , Ogereau David , Chaminade Nicole , Colard Alexandre , Aulard Sylvie 
Published: December 2005

Abstract
Sex-ratio meiotic drive is the preferential transmission of the X chromosome by XY males, which occurs in several Drosophila species and results in female-biased progeny. Although the trait has long been known to exist, its molecular basis remains completely unknown. Here we report a fine-mapping experiment designed to characterize the major drive locus on a sex-ratio X chromosome of Drosophila simulans originating from the Seychelles (XSR6). This primary locus was found to contain two interacting elements at least, both of which are required for drive expression. One of them was genetically tracked to a tandem duplication containing six annotated genes (Trf2, CG32712, CG12125, CG1440, CG12123, org-1), and the other to a candidate region located ∼110 kb away and spanning seven annotated genes. RT–PCR showed that all but two of these genes were expressed in the testis of both sex-ratio and standard males. In situ hybridization to polytene chromosomes revealed a complete association of the duplication with the sex-ratio trait in random samples of X chromosomes from Madagascar and Reunion.
Positive Selection Can Create False Hotspots of Recombination
Authors: Reed Floyd A , Tishkoff Sarah A 
Published: December 2005

Abstract
Simulations of positive directional selection, under parameter values appropriate for approximating human genetic diversity and rates of recombination, reveal that the effects of strong selective sweeps on patterns of linkage disequilibrium (LD) mimic the pattern expected with recombinant hotspots.
FluG-Dependent Asexual Development in Aspergillus nidulans Occurs via Derepression
Authors: Seo Jeong-Ah , Guan Yajun , Yu Jae-Hyuk 
Published: December 2005

Abstract
The asexual spore is one of the most crucial factors contributing to the fecundity and fitness of filamentous fungi. Although the developmental activator FluG was shown to be necessary for activation of asexual sporulation (conidiation) and production of the carcinogenic mycotoxin sterigmatocystin (ST) in the model filamentous fungus Aspergillus nidulans, the molecular mechanisms underlying the developmental switch have remained elusive. In this study, we report that the FluG-mediated conidiation in A. nidulans occurs via derepression. Suppressor analyses of fluG led to the identification of the sfgA gene encoding a novel protein with the Gal4-type Zn(II)2Cys6 binuclear cluster DNA-binding motif at the N terminus. Deletion (Δ) and 31 other loss-of-function sfgA mutations bypassed the need for fluG in conidiation and production of ST. Moreover, both ΔsfgA and ΔsfgA ΔfluG mutations resulted in identical phenotypes in growth, conidiation, and ST production, indicating that the primary role of FluG is to remove repressive effects imposed by SfgA. In accordance with the proposed regulatory role of SfgA, overexpression of sfgA inhibited conidiation and delayed/reduced expression of conidiation- and ST-specific genes. Genetic analyses demonstrated that SfgA functions downstream of FluG but upstream of transcriptional activators (FlbD, FlbC, FlbB, and BrlA) necessary for normal conidiation.
Genetic Analysis Connects SLX5 and SLX8 to the SUMO Pathway in Saccharomyces cerevisiae
Authors: Wang Zheng , Jones Grace Marie , Prelich Gregory 
Published: December 2005

Abstract
MOT1 encodes an essential ATPase that functions as a general transcriptional regulator in vivo by modulating TATA-binding protein (TBP) DNA-binding activity. Although MOT1 was originally identified both biochemically and in several genetic screens as a transcriptional repressor, a combination of subsequent genetic, chromatin immunoprecipitation, and microarray analysis suggested that MOT1 might also have an additional role in vivo as a transcriptional activator. To better understand the role(s) of MOT1 in vivo, we selected for genomic suppressors of a mot1 temperature-sensitive mutation. This selection identified mutations in SPT15 (TBP) and BUR6, both of which are clearly linked with MOT1 at the functional level. The vast majority of the suppressor mutations, however, unexpectedly occurred in six genes that encode known components of the SUMO pathway and in two other genes with unknown functions, SLX5 and SLX8. Additional results presented here, including extensive synthetic lethality observed between slx5Δ and slx8Δ and SUMO pathway mutations, suggest that SLX5 and SLX8 are new components or regulators of the SUMO pathway and that SUMO modification might have a general role in transcriptional regulation as part of the TBP regulatory network.
Effects of Chromosome-Specific Introgression in Upland Cotton on Fiber and Agronomic Traits
Authors: Saha Sukumar , Jenkins Johnie N , Wu Jixiang , McCarty Jack C , Gutiérrez Osman A , Percy Richard G , Cantrell Roy G , Stelly David M 
Published: December 2005

Abstract
Interspecific chromosome substitution is among the most powerful means of introgression and steps toward quantitative trait locus (QTL) identification. By reducing the genetic “noise” from other chromosomes, it greatly empowers the detection of genetic effects by specific chromosomes on quantitative traits. Here, we report on such results for 14 cotton lines (CS-B) with specific chromosomes or chromosome arms from G. barbadense L. substituted into G. hirsutum and chromosome-specific F2 families. Boll size, lint percentage, micronaire, 2.5% span length, elongation, strength, and yield were measured by replicated field experiments in five diverse environments and analyzed under an additive–dominance (AD) genetic model with genotype and environment interaction. Additive effects were significant for all traits and dominance effects were significant for all traits except 2.5% span length. CS-B25 had additive effects increasing fiber strength and fiber length and decreasing micronaire. CS-B16 and CS-B18 had additive effects related to reduced yields. The results point toward specific chromosomes of G. barbadense 3-79 as the probable locations of the genes that significantly affect quantitative traits of importance. Our results provided a scope to analyze individual chromosomes of the genome in homozygous and heterozygous conditions and thus detected novel effects of alleles controlling important QTL.
Involvement of Drosophila Uncoupling Protein 5 in Metabolism and Aging
Authors: Sánchez-Blanco Adolfo , Fridell Yih-Woei C , Helfand Stephen L 
Published: December 2005

AbstractA novel uncoupling protein, UCP5, has recently been characterized as a functional mitochondrial uncoupler in Drosophila. Here we demonstrate that UCP5 knockout (UCP5KO) flies are highly sensitive to starvation stress, a phenotype that can be reversed by ectopic neuronal expression of UCP5. UCP5KO flies live longer than controls on low-calorie diets, have a decreased level of fertility, and gain less weight than controls on high-calorie diets. However, isolated mitochondria from UCP5KO flies display the same respiration patterns as controls. Furthermore, total ATP levels in both UCP5KO and control flies are comparable. UCP5KO flies have a lower body composition of sugars, and during starvation stress their triglyceride reserves are depleted more rapidly than controls. Taken together, these data indicate that UCP5 is important to maintain metabolic homeostasis in the fly. We hypothesize that UCP5 influences hormonal control of metabolism.
Predicting Chromosomal Locations of Genetically Mapped Loci in Maize Using the Morgan2McClintock Translator
Authors: Lawrence Carolyn J , Seigfried Trent E , Bass Hank W , Anderson Lorinda K 
Published: December 2005

Abstract
The Morgan2McClintock Translator permits prediction of meiotic pachytene chromosome map positions from recombination-based linkage data using recombination nodule frequency distributions. Its outputs permit estimation of DNA content between mapped loci and help to create an integrated overview of the maize nuclear genome structure.