bluuebunny/crossref_metadata_2025 huggingface dataset:
Bird and Mammal Sex-Chromosome Orthologs Map to the Same Autosomal Region in a Salamander (Ambystoma)
Authors: Smith Jeramiah J , Voss S Randal
Published: July 2007

We tested hypotheses concerning the origin of bird and mammal sex chromosomes by mapping the location of amniote sex-chromosome loci in a salamander amphibian (Ambystoma). We found that ambystomatid orthologs of human X and chicken Z sex chromosomes map to neighboring regions of a common Ambystoma linkage group 2 (ALG2). We show statistically that the proportion of human X and chicken Z orthologs observed on ALG2 is significantly different from the proportion that would be expected by chance. We further show that conserved syntenies between ALG2 and amniote chromosomes are identified as overlapping conserved syntenies when all available chicken (N = 3120) and human (N = 14,922) RefSeq orthologs are reciprocally compared. In particular, the data suggest that chromosomal regions from chicken chromosomes (GGA) Z and 4 and from human chromosomes (HSA) 9, 4, X, 5, and 8 were linked ancestrally. A more distant outgroup comparison with the pufferfish Tetraodon nigroviridis reveals ALG2/GGAZ/HSAX syntenies among three pairs of ancestral chromosome duplicates. Overall, our results suggest that sex chromosomal regions of birds and mammals were recruited from a common ancestral chromosome, and thus our findings conflict with the currently accepted hypothesis of separate autosomal origins. We note that our results were obtained using the most immediate outgroup to the amniote clade (mammals, birds, and other reptiles) while the currently accepted hypothesis is primarily based upon conserved syntenies between in-group taxa (birds and mammals). Our study illustrates the importance of an amphibian outgroup perspective in identifying ancestral amniote gene orders and in reconstructing patterns of vertebrate sex-chromosome evolution.
On the Choice of Genetic Distance in Spatial-Genetic Studies
Authors: Fearnhead Paul
Published: July 2007

We look at how to choose genetic distance so as to maximize the power of detecting spatial structure. We answer this question through analyzing two population genetic models that allow for a spatially structured population in a continuous habitat. These models, like most that incorporate spatial structure, can be characterized by a separation of timescales: the history of the sample can be split into a scattering and a collecting phase, and it is only during the scattering phase that the spatial locations of the sample affect the coalescence times. Our results suggest that the optimal choice of genetic distance is based upon splitting a DNA sequence into segments and counting the number of segments at which two sequences differ. The size of these segments depends on the length of the scattering phase for the population genetic model.
Natural Variation for Alleles Under Epigenetic Control by the Maize ChromomethylaseZmet2
Authors: Makarevitch Irina , Stupar Robert M , Iniguez A Leonardo , Haun William J , Barbazuk W Brad , Kaeppler Shawn M , Springer Nathan M
Published: July 2007

The contribution of epigenetic alterations to natural variation for gene transcription levels remains unclear. In this study, we investigated the functional targets of the maize chromomethylase ZMET2 in multiple inbred lines to determine whether epigenetic changes conditioned by this chromomethylase are conserved or variable within the species. Gene expression microarrays were hybridized with RNA samples from the inbred lines B73 and Mo17 and from near-isogenic derivatives containing the loss-of-function allele zmet2-m1. A set of 126 genes that displayed statistically significant differential expression in zmet2 mutants relative to wild-type plants in at least one of the two genetic backgrounds was identified. Analysis of the transcript levels in both wild-type and mutant individuals revealed that only 10% of these genes were affected in zmet2 mutants in both B73 and Mo17 genetic backgrounds. Over 80% of the genes with expression patterns affected by zmet2 mutations display variation for gene expression between wild-type B73 and Mo17 plants. Further analysis was performed for 7 genes that were transcriptionally silent in wild-type B73, but expressed in B73 zmet2-m1, wild-type Mo17, and Mo17 zmet2-m1 lines. Mapping experiments confirmed that the expression differences in wild-type B73 relative to Mo17 inbreds for these genes were caused by cis-acting regulatory variation. Methylation-sensitive PCR and bisulfite sequencing demonstrated that for 5 of these genes the CpNpG methylation in the wild-type B73 genetic background was substantially decreased in the B73 zmet2-m1 mutant and in wild-type Mo17. A survey of eight maize inbreds reveals that each of these 5 genes exhibit transcriptionally silent and methylated states in some inbred lines and unmethylated, expressed states in other inbreds, providing evidence for natural variation in epigenetic states for some maize genes.
A Genomic Screen in Yeast Reveals Novel Aspects of Nonstop mRNA Metabolism
Authors: Wilson Marenda A , Meaux Stacie , van Hoof Ambro
Published: July 2007

Nonstop mRNA decay, a specific mRNA surveillance pathway, rapidly degrades transcripts that lack in-frame stop codons. The cytoplasmic exosome, a complex of 3′–5′ exoribonucleases involved in RNA degradation and processing events, degrades nonstop transcripts. To further understand how nonstop mRNAs are recognized and degraded, we performed a genomewide screen for nonessential genes that are required for nonstop mRNA decay. We identified 16 genes that affect the expression of two different nonstop reporters. Most of these genes affected the stability of a nonstop mRNA reporter. Additionally, three mutations that affected nonstop gene expression without stabilizing nonstop mRNA levels implicated the proteasome. This finding not only suggested that the proteasome may degrade proteins encoded by nonstop mRNAs, but also supported previous observations that rapid decay of nonstop mRNAs cannot fully explain the lack of the encoded proteins. Further, we show that the proteasome and Ski7p affected expression of nonstop reporter genes independently of each other. In addition, our results implicate inositol 1,3,4,5,6-pentakisphosphate as an inhibitor of nonstop mRNA decay.
Comparisons Among Two Fertile and Three Male-Sterile Mitochondrial Genomes of Maize
Authors: Allen James O , Fauron Christiane M , Minx Patrick , Roark Leah , Oddiraju Swetha , Lin Guan Ning , Meyer Louis , Sun Hui , Kim Kyung , Wang Chunyan , Du Feiyu , Xu Dong , Gibson Michael , Cifrese Jill , Clifton Sandra W , Newton Kathleen J
Published: July 2007

We have sequenced five distinct mitochondrial genomes in maize: two fertile cytotypes (NA and the previously reported NB) and three cytoplasmic-male-sterile cytotypes (CMS-C, CMS-S, and CMS-T). Their genome sizes range from 535,825 bp in CMS-T to 739,719 bp in CMS-C. Large duplications (0.5–120 kb) account for most of the size increases. Plastid DNA accounts for 2.3–4.6% of each mitochondrial genome. The genomes share a minimum set of 51 genes for 33 conserved proteins, three ribosomal RNAs, and 15 transfer RNAs. Numbers of duplicate genes and plastid-derived tRNAs vary among cytotypes. A high level of sequence conservation exists both within and outside of genes (1.65–7.04 substitutions/10 kb in pairwise comparisons). However, sequence losses and gains are common: integrated plastid and plasmid sequences, as well as noncoding “native” mitochondrial sequences, can be lost with no phenotypic consequence. The organization of the different maize mitochondrial genomes varies dramatically; even between the two fertile cytotypes, there are 16 rearrangements. Comparing the finished shotgun sequences of multiple mitochondrial genomes from the same species suggests which genes and open reading frames are potentially functional, including which chimeric ORFs are candidate genes for cytoplasmic male sterility. This method identified the known CMS-associated ORFs in CMS-S and CMS-T, but not in CMS-C.
Segregation Analyses of Partial Self-Incompatibility in Self and Cross Progeny of Solanum carolinense Reveal a Leaky S-Allele
Authors: Mena-Ali Jorge I , Stephenson Andrew G
Published: July 2007

Natural populations of self-incompatible species often exhibit marked phenotypic variation among individuals in the strength of self-incompatibility (SI). In previous studies, we found that the strength of the SI response in Solanum carolinense, a weedy invasive with RNase-mediated SI, is a plastic trait. Selfing can be particularly important for weeds and other successional species that typically undergo repeated colonization and local extinction events and whose population sizes are often small. We applied a PCR-based protocol to identify the S-alleles present in 16 maternal genotypes and their offspring and performed a two-generation greenhouse study to determine whether variation in the strength of SI is due to the existence of weak and strong S-alleles differing in their ability to recognize and reject self-pollen. We found that allele S9 sets significantly more self seed than the other S-alleles in the population we sampled and that its ability to self is not dependent on interactions with other S-alleles. Our data suggest that the observed variations in self-fertility are likely due to factors that directly influence the expression of SI by altering the translation, turnover, or activity of the S-RNase. The variability in the strength of SI among individuals that we have observed in this and our previous studies raises the possibility that plasticity in the strength of SI in S. carolinense may play a role in the colonization and establishment of this weedy species.
Meiotic Pairing and Disjunction of Mini-X Chromosomes in Drosophila Is Mediated by 240-bp rDNA Repeats and the Homolog Conjunction Proteins SNM and MNM
Authors: Thomas Sharon E , McKee Bruce D
Published: July 2007

In most eukaryotes, segregation of homologous chromosomes during meiosis is dependent on crossovers that occur while the homologs are intimately paired during early prophase. Crossovers generate homolog connectors known as chiasmata that are stabilized by cohesion between sister-chromatid arms. In Drosophila males, homologs pair and segregate without recombining or forming chiasmata. Stable pairing of homologs is dependent on two proteins, SNM and MNM, that associate with chromosomes throughout meiosis I until their removal at anaphase I. SNM and MNM localize to the rDNA region of the X–Y pair, which contains 240-bp repeats that have previously been shown to function as cis-acting chromosome pairing/segregation sites. Here we show that heterochromatic mini-X chromosomes lacking native rDNA but carrying transgenic 240-bp repeat arrays segregate preferentially from full-length sex chromosomes and from each other. Mini-X pairs do not form autonomous bivalents but do associate at high frequency with the X–Y bivalent to form trivalents and quadrivalents. Both disjunction of mini-X pairs and multivalent formation are dependent on the presence of SNM and MNM. These results imply that 240-bp repeats function to mediate association of sex chromosomes with SNM and MNM.
Positive Selection Near an Inversion Breakpoint on the Neo-XChromosome ofDrosophila americana
Authors: Evans Amy L , Mena Paulina A , McAllister Bryant F
Published: July 2007

Unique features of heteromorphic sex chromosomes are produced as a consequence of sex-linked transmission. Alternative models concerning the evolution of sex chromosomes can be classified in terms of genetic drift or positive selection being the primary mechanism of divergence between this chromosomal pair. This study examines early changes on a newly acquired chromosomal arm of the X in Drosophila americana, which was derived from a centromeric fusion between the ancestral X and previously autosomal chromosome 4 (element B). Breakpoints of a chromosomal inversion In(4)a, which is restricted to the neo-X, are identified and used to guide a sequence analysis along chromosome 4. Loci flanking the distal breakpoint exhibit patterns of sequence diversity consistent with neutral evolution, yet loci near the proximal breakpoint reveal distinct imprints of positive selection within the neo-X chromosomal class containing In(4)a. Data from six separate positions examined throughout the proximal region reveal a pattern of recent turnover driven by two independent sweeps among chromosomes with the inverted gene arrangement. Selection-mediated establishment of an extended haplotype associated with recombination-suppressing inversions on the neo-X indicates a pattern of active coadaptation apparently initiated by X-linked transmission and potentially sustained by intralocus sexual conflict.
Haplotype Inference in General Pedigrees Using the Cluster Variation Method
Authors: Albers Cornelis A , Heskes Tom , Kappen Hilbert J
Published: July 2007

We present CVMHAPLO, a probabilistic method for haplotyping in general pedigrees with many markers. CVMHAPLO reconstructs the haplotypes by assigning in every iteration a fixed number of the ordered genotypes with the highest marginal probability, conditioned on the marker data and ordered genotypes assigned in previous iterations. CVMHAPLO makes use of the cluster variation method (CVM) to efficiently estimate the marginal probabilities. We focused on single-nucleotide polymorphism (SNP) markers in the evaluation of our approach. In simulated data sets where exact computation was feasible, we found that the accuracy of CVMHAPLO was high and similar to that of maximum-likelihood methods. In simulated data sets where exact computation of the maximum-likelihood haplotype configuration was not feasible, the accuracy of CVMHAPLO was similar to that of state of the art Markov chain Monte Carlo (MCMC) maximum-likelihood approximations when all ordered genotypes were assigned and higher when only a subset of the ordered genotypes was assigned. CVMHAPLO was faster than the MCMC approach and provided more detailed information about the uncertainty in the inferred haplotypes. We conclude that CVMHAPLO is a practical tool for the inference of haplotypes in large complex pedigrees.
Single Nucleotide Polymorphisms and Linkage Disequilibrium in Sunflower
Authors: Kolkman Judith M , Berry Simon T , Leon Alberto J , Slabaugh Mary B , Tang Shunxue , Gao Wenxiang , Shintani David K , Burke John M , Knapp Steven J
Published: July 2007

Genetic diversity in modern sunflower (Helianthus annuus L.) cultivars (elite oilseed inbred lines) has been shaped by domestication and breeding bottlenecks and wild and exotic allele introgression−the former narrowing and the latter broadening genetic diversity. To assess single nucleotide polymorphism (SNP) frequencies, nucleotide diversity, and linkage disequilibrium (LD) in modern cultivars, alleles were resequenced from 81 genic loci distributed throughout the sunflower genome. DNA polymorphisms were abundant; 1078 SNPs (1/45.7 bp) and 178 insertions-deletions (INDELs) (1/277.0 bp) were identified in 49.4 kbp of DNA/genotype. SNPs were twofold more frequent in noncoding (1/32.1 bp) than coding (1/62.8 bp) sequences. Nucleotide diversity was only slightly lower in inbred lines (θ = 0.0094) than wild populations (θ = 0.0128). Mean haplotype diversity was 0.74. When extraploted across the genome (∼3500 Mbp), sunflower was predicted to harbor at least 76.4 million common SNPs among modern cultivar alleles. LD decayed more slowly in inbred lines than wild populations (mean LD declined to 0.32 by 5.5 kbp in the former, the maximum physical distance surveyed), a difference attributed to domestication and breeding bottlenecks. SNP frequencies and LD decay are sufficient in modern sunflower cultivars for very high-density genetic mapping and high-resolution association mapping.
Structure/Function Analysis of the Phosphatidylinositol-3-Kinase Domain of Yeast Tra1
Authors: Mutiu A Irina , Hoke Stephen M T , Genereaux Julie , Hannam Carol , MacKenzie Katherine , Jobin-Robitaille Olivier , Guzzo Julie , Côté Jacques , Andrews Brenda , Haniford David B , Brandl Christopher J
Published: July 2007

Tra1 is an essential component of the Saccharomyces cerevisiae SAGA and NuA4 complexes. Using targeted mutagenesis, we identified residues within its C-terminal phosphatidylinositol-3-kinase (PI3K) domain that are required for function. The phenotypes of tra1-P3408A, S3463A, and SRR3413-3415AAA included temperature sensitivity and reduced growth in media containing 6% ethanol or calcofluor white or depleted of phosphate. These alleles resulted in a twofold or greater change in expression of ∼7% of yeast genes in rich media and reduced activation of PHO5 and ADH2 promoters. Tra1-SRR3413 associated with components of both the NuA4 and SAGA complexes and with the Gal4 transcriptional activation domain similar to wild-type protein. Tra1-SRR3413 was recruited to the PHO5 promoter in vivo but gave rise to decreased relative amounts of acetylated histone H3 and histone H4 at SAGA and NuA4 regulated promoters. Distinct from other components of these complexes, tra1-SRR3413 resulted in generation-dependent telomere shortening and synthetic slow growth in combination with deletions of a number of genes with roles in membrane-related processes. While the tra1 alleles have some phenotypic similarities with deletions of SAGA and NuA4 components, their distinct nature may arise from the simultaneous alteration of SAGA and NuA4 functions.
Genomewide Discovery and Classification of Candidate Ovarian Fertility Genes in the Mouse
Authors: Gallardo Teresa D , John George B , Shirley Lane , Contreras Cristina M , Akbay Esra A , Haynie J Marshall , Ward Samuel E , Shidler Meredith J , Castrillon Diego H
Published: July 2007

Female infertility syndromes are among the most prevalent chronic health disorders in women, but their genetic basis remains unknown because of uncertainty regarding the number and identity of ovarian factors controlling the assembly, preservation, and maturation of ovarian follicles. To systematically discover ovarian fertility genes en masse, we employed a mouse model (Foxo3) in which follicles are assembled normally but then undergo synchronous activation. We developed a microarray-based approach for the systematic discovery of tissue-specific genes and, by applying it to Foxo3 ovaries and other samples, defined a surprisingly large set of ovarian factors (n = 348, ∼1% of the mouse genome). This set included the vast majority of known ovarian factors, 44% of which when mutated produce female sterility phenotypes, but most were novel. Comparative profiling of other tissues, including microdissected oocytes and somatic cells, revealed distinct gene classes and provided new insights into oogenesis and ovarian function, demonstrating the utility of our approach for tissue-specific gene discovery. This study will thus facilitate comprehensive analyses of follicle development, ovarian function, and female infertility.
Distinctly Different Sex Ratios in African and European Populations ofDrosophila melanogasterInferred From Chromosomewide Single Nucleotide Polymorphism Data
Authors: Hutter Stephan , Li Haipeng , Beisswanger Steffen , De Lorenzo David , Stephan Wolfgang
Published: July 2007

It has been hypothesized that the ratio of X-linked to autosomal sequence diversity is influenced by unequal sex ratios in Drosophila melanogaster populations. We conducted a genome scan of single nucleotide polymorphism (SNP) of 378 autosomal loci in a derived European population and of a subset of 53 loci in an ancestral African population. On the basis of these data and our already available X-linked data, we used a coalescent-based maximum-likelihood method to estimate sex ratios and demographic histories simultaneously for both populations. We confirm our previous findings that the African population experienced a population size expansion while the European population suffered a population size bottleneck. Our analysis also indicates that the female population size in Africa is larger than or equal to the male population size. In contrast, the European population shows a huge excess of males. This unequal sex ratio and the bottleneck alone, however, cannot account for the overly strong decrease of X-linked diversity in the European population (compared to the reduction on the autosome). The patterns of the frequency spectrum and the levels of linkage disequilibrium observed in Europe suggest that, in addition, positive selection must have acted in the derived population.
Reduced Levels of Su(var)3-9 But Not Su(var)2-5 (HP1) Counteract the Effects on Chromatin Structure and Viability in Loss-of-Function Mutants of the JIL-1 Histone H3S10 Kinase
Authors: Deng Huai , Bao Xiaomin , Zhang Weiguo , Girton Jack , Johansen Jørgen , Johansen Kristen M
Published: July 2007

It has recently been demonstrated that activity of the essential JIL-1 histone H3S10 kinase is a major regulator of chromatin structure and that it functions to maintain euchromatic domains while counteracting heterochromatization and gene silencing. In the absence of JIL-1 kinase activity, the major heterochromatin markers histone H3K9me2 and HP1 spread in tandem to ectopic locations on the chromosome arms. In this study, we show that the lethality as well as some of the chromosome morphology defects associated with the null JIL-1 phenotype to a large degree can be rescued by reducing the dose of the Su(var)3-9 gene. This effect was observed with three different alleles of Su(var)3-9, strongly suggesting it is specific to Su(var)3-9 and not to second site modifiers. This is in contrast to similar experiments performed with alleles of the Su(var)2-5 gene that codes for HP1 in Drosophila where no genetic interactions were detectable between JIL-1 and Su(var)2-5. Taken together, these findings indicate that while Su(var)3-9 histone methyltransferase activity is a major factor in the lethality and chromatin structure perturbations associated with loss of the JIL-1 histone H3S10 kinase, these effects are likely to be uncoupled from HP1.
Natural Variation of ebony Gene Controlling Thoracic Pigmentation in Drosophila melanogaster
Authors: Takahashi Aya , Takahashi Kuniaki , Ueda Ryu , Takano-Shimizu Toshiyuki
Published: July 2007

We identified the causal genetic variation for the difference in the thoracic trident pigmentation intensity between two wild-derived strains of Drosophila melanogaster. It was found to be the difference in expression level of ebony, which codes for an enzyme in the melanin-synthesis pathway and has pleiotropic effects on vision and behavior.
Using Quantitative Trait Loci Results to Discriminate Among Crosses on the Basis of Their Progeny Mean and Variance
Authors: Zhong Shengqiang , Jannink Jean-Luc
Published: July 2007

To develop inbred lines, parents are crossed to generate segregating populations from which superior inbred progeny are selected. The value of a particular cross thus depends on the expected performance of its best progeny, which we call the superior progeny value. Superior progeny value is a linear combination of the mean of the cross's progeny and their standard deviation. In this study we specify theory to predict a cross's progeny standard deviation from QTL results and explore analytically and by simulation the variance of that standard deviation under different genetic models. We then study the impact of different QTL analysis methods on the prediction accuracy of a cross's superior progeny value. We show that including all markers, rather than only markers with significant effects, improves the prediction. Methods that account for the uncertainty of the QTL analysis by integrating over the posterior distributions of effect estimates also produce better predictions than methods that retain only point estimates from the QTL analysis. The utility of including estimates of a cross's among-progeny standard deviation in the prediction increases with increasing heritability and marker density but decreasing genome size and QTL number. This utility is also higher if crosses are envisioned only among the best parents rather than among all parents. Nevertheless, we show that among crosses the variance of progeny means is generally much greater than the variance of progeny standard deviations, restricting the utility of estimates of progeny standard deviations to a relatively small parameter space.
Molecular Genetic Analysis of Two Loci (Ity2andIty3) Involved in the Host Response to Infection With Salmonella Typhimurium Using Congenic Mice and Expression Profiling
Authors: Sancho-Shimizu Vanessa , Khan Rabia , Mostowy Serge , Larivière Line , Wilkinson Rosalie , Riendeau Noémie , Behr Marcel , Malo Danielle
Published: July 2007

Numerous genes have been identified to date that contribute to the host response to systemic Salmonella Typhimurium infection in mice. We have previously identified two loci, Ity2 and Ity3, that control survival to Salmonella infection in the wild-derived inbred MOLF/Ei mouse using a (C57BL/6J × MOLF/Ei)F2cross. We validated the existence of these two loci by creating congenic mice carrying each quantitative trait locus (QTL) in isolation. Subcongenic mice generated for each locus allowed us to define the critical intervals underlying Ity2 and Ity3. Furthermore, expression profiling was carried out with the aim of identifying differentially expressed genes within the critical intervals as potential candidate genes. Genomewide expression arrays were used to interrogate expression differences in the Ity2 congenics, leading to the identification of a new candidate gene (Havcr2, hepatitis A virus cellular receptor 2). Interval-specific oligonucleotide arrays were created for Ity3, identifying one potential candidate gene (Chi3l1, chitinase 3-like 1) to be pursued further. The combination of the use of congenics in QTL confirmation and fine mapping and in the identification of candidate genes by expression profiling has been successful and represents a step toward quantitative gene(s) identification.
Genomewide Rapid Association Using Mixed Model and Regression: A Fast and Simple Method For Genomewide Pedigree-Based Quantitative Trait Loci Association Analysis
Authors: Aulchenko Yurii S , de Koning Dirk-Jan , Haley Chris
Published: July 2007

For pedigree-based quantitative trait loci (QTL) association analysis, a range of methods utilizing within-family variation such as transmission-disequilibrium test (TDT)-based methods have been developed. In scenarios where stratification is not a concern, methods exploiting between-family variation in addition to within-family variation, such as the measured genotype (MG) approach, have greater power. Application of MG methods can be computationally demanding (especially for large pedigrees), making genomewide scans practically infeasible. Here we suggest a novel approach for genomewide pedigree-based quantitative trait loci (QTL) association analysis: genomewide rapid association using mixed model and regression (GRAMMAR). The method first obtains residuals adjusted for family effects and subsequently analyzes the association between these residuals and genetic polymorphisms using rapid least-squares methods. At the final step, the selected polymorphisms may be followed up with the full measured genotype (MG) analysis. In a simulation study, we compared type 1 error, power, and operational characteristics of the proposed method with those of MG and TDT-based approaches. For moderately heritable (30%) traits in human pedigrees the power of the GRAMMAR and the MG approaches is similar and is much higher than that of TDT-based approaches. When using tabulated thresholds, the proposed method is less powerful than MG for very high heritabilities and pedigrees including large sibships like those observed in livestock pedigrees. However, there is little or no difference in empirical power of MG and the proposed method. In any scenario, GRAMMAR is much faster than MG and enables rapid analysis of hundreds of thousands of markers.
Multilevel Selection 3: Modeling the Effects of Interacting Individuals as a Function of Group Size
Authors: Hadfield Jarrod D , Wilson Alastair J
Published: July 2007

Bijma  et al. (2007a,b) presented a quantitative genetic theory of multilevel selection and showed how to estimate the relevant parameters using standard restricted maximum-likelihood (REML) methodology. Extending their results we develop a wider class of models that provide a more realistic framework for capturing the effects of interacting individuals. These models also make use of standard REML techniques and include the original model as a special case.
Misregulation of the Kinesin-like Protein Subito Induces Meiotic Spindle Formation in the Absence of Chromosomes and Centrosomes
Authors: Jang Janet K , Rahman Taslima , Kober Vanessa S , Cesario Jeffry , McKim Kim S
Published: July 2007

Bipolar spindles assemble in the absence of centrosomes in the oocytes of many species. In Drosophila melanogaster oocytes, the chromosomes have been proposed to initiate spindle assembly by nucleating or capturing microtubules, although the mechanism is not understood. An important contributor to this process is Subito, which is a kinesin-6 protein that is required for bundling interpolar microtubules located within the central spindle at metaphase I. We have characterized the domains of Subito that regulate its activity and its specificity for antiparallel microtubules. This analysis has revealed that the C-terminal domain may interact independently with microtubules while the motor domain is required for maintaining the interaction with the antiparallel microtubules. Surprisingly, deletion of the N-terminal domain resulted in a Subito protein capable of promoting the assembly of bipolar spindles that do not include centrosomes or chromosomes. Bipolar acentrosomal spindle formation during meiosis in oocytes may be driven by the bundling of antiparallel microtubules. Furthermore, these experiments have revealed evidence of a nuclear- or chromosome-based signal that acts at a distance to activate Subito. Instead of the chromosomes directly capturing microtubules, signals released upon nuclear envelope breakdown may activate proteins like Subito, which in turn bundles together microtubules.
Triple Mutants Uncover Three New Genes Required for Social Motility inMyxococcus xanthus
Authors: Youderian Philip , Hartzell Patricia L
Published: July 2007

The bacterium Myxococcus xanthus glides over surfaces using two different locomotive mechanisms, called S (social) and A (adventurous) motility that enable cells to move both as groups and as individuals. Neither mechanism involves flagella. The functions of these two motors are coordinated by the activity of a small Ras-like protein, encoded by the mglA gene. The results of previous studies of a second-site suppressor of the mglA-8 missense mutation masK-815 indicate that MglA interacts with a protein tyrosine kinase, MasK, to control social motility. Sequence analysis of the sites of 12 independent insertions of the transposon magellan-4 that result in the loss of motility in an M. xanthus mglA-8 masK-815 double mutant shows that nine of these 12 insertions are in genes known to be required for S gliding motility. This result confirms that the masK-815 suppressor restores S but not A motility. Three of the 12 insertions define three new genes required for S motility and show that the attachment of heptose to the lipopolysaccharide inner core, an ortholog of the CheR methyltransferase, and a large protein with YD repeat motifs, are required for S motility. When these three insertions are backcrossed into an otherwise wild-type genetic background, their recombinants are found to have defects in S, but not, A motility. The spectrum of magellan-4 insertions that lead to the loss of S motility in the mglA-8 masK-815 double mutant background is different than that resulting from a previous mutant hunt starting with a different (A mutant) genetic background, suggesting that the number of genes required for S motility in M. xanthus is quite large.
Schizosaccharomyces pombe Switches Mating Type by the Synthesis-Dependent Strand-Annealing Mechanism
Authors: Yamada-Inagawa Tomoko , Klar Amar J S , Dalgaard Jacob Z
Published: July 2007

Schizosaccharomyces pombe cells can switch between two mating types, plus (P) and minus (M). The change in cell type occurs due to a replication-coupled recombination event that transfers genetic information from one of the silent-donor loci, mat2P or mat3M, into the expressed mating-type determining mat1 locus. The mat1 locus can as a consequence contain DNA encoding either P or M information. A molecular mechanism, known as synthesis-dependent strand annealing, has been proposed for the underlying recombination event. A key feature of this model is that only one DNA strand of the donor locus provides the information that is copied into the mat1. Here we test the model by constructing strains that switch using two different mutant P cassettes introduced at the donor loci, mat2 and mat3. We show that in such strains wild-type P-cassette DNA is efficiently generated at mat1 through heteroduplex DNA formation and repair. The present data provide an in vivo genetic test of the proposed molecular recombination mechanism.
Isolation and Characterization of Saccharomyces cerevisiae Mutants Defective in Chromosome Transmission in an Undergraduate Genetics Research Course
Authors: Sleister Heidi Major
Published: July 2007

An upper-level genetics research course was developed to expose undergraduates to investigative science. Students are immersed in a research project with the ultimate goal of identifying proteins important for chromosome transmission in mitosis. After mutagenizing yeast Saccharomyces cerevisiae cells, students implement a genetic screen that allows for visual detection of mutants with an increased loss of an ADE2-marked yeast artificial chromosome (YAC). Students then genetically characterize the mutants and begin efforts to identify the defective genes in these mutants. While engaged in this research project, students practice a variety of technical skills in both classical and molecular genetics. Furthermore, students learn to collaborate and gain experience in sharing scientific findings with others in the form of written papers, poster presentations, and oral presentations. Previous students indicated that, relative to a traditional laboratory course, this research course improved their understanding of scientific concepts and technical skills and helped them make connections between concepts. Moreover, this course allowed students to experience scientific inquiry and was influential for students as they considered future endeavors.
E(var)3-9ofDrosophila melanogasterEncodes a Zinc Finger Protein
Authors: Weiler Karen S
Published: July 2007

The importance of a gene's natural chromatin environment for its normal expression is poignantly illustrated when a change in chromosome position results in variable gene repression, such as is observed in position effect variegation (PEV) when the Drosophila melanogaster white (w) gene is juxtaposed with heterochromatin. The Enhancer of variegation 3-9 [E(var)3-9] gene was one of over a hundred loci identified in screens for mutations that dominantly modify PEV. Haploinsufficiency for E(var)3-9 enhances wm4 variegation, as would be expected from increased heterochromatin formation. To clarify the role of E(var)3-9 in chromosome structure, the gene has been cloned and its mutant alleles characterized. The involvement of E(var)3-9 in structure determination was supported by its reciprocal effects on euchromatic and heterochromatic PEV; E(var)3-9 mutations increased expression of a variegating heterochromatic gene in two tissue types. E(var)3-9 mutations also had a recessive phenotype, maternal effect lethality, which implicated E(var)3-9 function in an essential process during embryogenesis. Both phenotypes of E(var)3-9 mutations were consistent with its proposed function in promoting normal chromosome structure. The cloning of E(var)3-9 by classical genetic methods revealed that it encodes a protein with multiple zinc fingers, but otherwise novel sequence.
Caenorhabditis elegans SDF-9 Enhances Insulin/Insulin-Like Signaling Through Interaction With DAF-2
Authors: Jensen Victor L , Albert Patrice S , Riddle Donald L
Published: July 2007

SDF-9 is a modulator of Caenorhabditis elegans insulin/IGF-1 signaling that may interact directly with the DAF-2 receptor. SDF-9 is a tyrosine phosphatase-like protein that, when mutated, enhances many partial loss-of-function mutants in the dauer pathway except for the temperature-sensitive mutant daf-2(m41). We propose that SDF-9 stabilizes the active phosphorylated state of DAF-2 or acts as an adaptor protein to enhance insulin-like signaling.
Reconciling Strong Stabilizing Selection with the Maintenance of Genetic Variation in a Natural Population of Black Field Crickets (Teleogryllus commodus)
Authors: Hunt John , Blows Mark W , Zajitschek Felix , Jennions Michael D , Brooks Robert
Published: July 2007

Genetic variation in single traits, including those closely related to fitness, is pervasive and generally high. By contrast, theory predicts that several forms of selection, including stabilizing selection, will eliminate genetic variation. Stabilizing selection in natural populations tends to be stronger than that assumed in theoretical models of the maintenance of genetic variation. The widespread presence of genetic variation in the presence of strong stabilizing selection is a persistent problem in evolutionary genetics that currently has no compelling explanation. The recent insight that stabilizing selection often acts most strongly on trait combinations via correlational selection may reconcile this problem. Here we show that for a set of male call properties in the cricket Teleogryllus commodus, the pattern of multivariate stabilizing sexual selection is closely associated with the degree of additive genetic variance. The multivariate trait combinations experiencing the strongest stabilizing selection harbored very little genetic variation while combinations under weak selection contained most of the genetic variation. Our experiment provides empirical support for the prediction that a small number of trait combinations experiencing strong stabilizing selection will have reduced genetic variance and that genetically independent trait combinations experiencing weak selection can simultaneously harbor much higher levels of genetic variance.
The Population Genetic Structure of Clonal Organisms Generated by Exponentially Bounded and Fat-Tailed Dispersal
Authors: Wingen Luzie U , Brown James K M , Shaw Michael W
Published: July 2007

Long-distance dispersal (LDD) plays an important role in many population processes like colonization, range expansion, and epidemics. LDD of small particles like fungal spores is often a result of turbulent wind dispersal and is best described by functions with power-law behavior in the tails (“fat tailed”). The influence of fat-tailed LDD on population genetic structure is reported in this article. In computer simulations, the population structure generated by power-law dispersal with exponents in the range of −2 to −1, in distinct contrast to that generated by exponential dispersal, has a fractal structure. As the power-law exponent becomes smaller, the distribution of individual genotypes becomes more self-similar at different scales. Common statistics like GST are not well suited to summarizing differences between the population genetic structures. Instead, fractal and self-similarity statistics demonstrated differences in structure arising from fat-tailed and exponential dispersal. When dispersal is fat tailed, a log–log plot of the Simpson index against distance between subpopulations has an approximately constant gradient over a large range of spatial scales. The fractal dimension D2 is linearly inversely related to the power-law exponent, with a slope of ∼ −2. In a large simulation arena, fat-tailed LDD allows colonization of the entire space by all genotypes whereas exponentially bounded dispersal eventually confines all descendants of a single clonal lineage to a relatively small area.
Empirical Bayes Inference of Pairwise FST and Its Distribution in the Genome
Authors: Kitada Shuichi , Kitakado Toshihide , Kishino Hirohisa
Published: July 2007

Populations often have very complex hierarchical structure. Therefore, it is crucial in genetic monitoring and conservation biology to have a reliable estimate of the pattern of population subdivision. FST's for pairs of sampled localities or subpopulations are crucial statistics for the exploratory analysis of population structures, such as cluster analysis and multidimensional scaling. However, the estimation of FST is not precise enough to reliably estimate the population structure and the extent of heterogeneity. This article proposes an empirical Bayes procedure to estimate locus-specific pairwise FST's. The posterior mean of the pairwise FST can be interpreted as a shrinkage estimator, which reduces the variance of conventional estimators largely at the expense of a small bias. The global FST of a population generally varies among loci in the genome. Our maximum-likelihood estimates of global FST's can be used as sufficient statistics to estimate the distribution of FST in the genome. We demonstrate the efficacy and robustness of our model by simulation and by an analysis of the microsatellite allele frequencies of the Pacific herring. The heterogeneity of the global FST in the genome is discussed on the basis of the estimated distribution of the global FST for the herring and examples of human single nucleotide polymorphisms (SNPs).
A Genetic Screen For DNA Double-Strand Break Repair Mutations in Drosophila
Authors: Wei Debbie S , Rong Yikang S
Published: July 2007

The study of DNA double-strand break (DSB) repair has been greatly facilitated by the use of rare-cutting endonucleases, which induce a break precisely at their cut sites that can be strategically placed in the genome. We previously established such a system in Drosophila and showed that the yeast I-SceI enzyme cuts efficiently in Drosophila cells and those breaks are effectively repaired by conserved mechanisms. In this study, we determined the genetic requirements for the repair of this I-SceI-induced DSB in the germline. We show that Drosophila Rad51 and Rad54 are both required for homologous repair by gene conversion, but are dispensable for single-strand annealing repair. We provided evidence suggesting that Rad51 is more stringently required than Rad54 for intersister gene conversion. We uncovered a significant role of DNA ligase IV in nonhomologous end joining. We conducted a screen for candidate mutations affecting DSB repair and discovered novel mutations in genes that include mutagen sensitive 206, single-strand annealing reducer, and others. In addition, we demonstrated an intricate balance among different repair pathways in which the cell differentially utilizes repair mechanisms in response to both changes in the genomic environment surrounding the break and deficiencies in one or the other repair pathways.
Complex Genetic Changes in Strains of Saccharomyces cerevisiae Derived by Selection in the Laboratory
Authors: Witten Joshua T , Chen Christina T L , Cohen Barak A
Published: July 2007

Selection of model organisms in the laboratory has the potential to generate useful substrates for testing evolutionary theories. These studies generally employ relatively long-term selections with weak selective pressures to allow the accumulation of multiple adaptations. In contrast to this approach, we analyzed two strains of Saccharomyces cerevisiae that were selected for resistance to multiple stress challenges by a rapid selection scheme to test whether the variation between rapidly selected strains might also be useful in evolutionary studies. We found that resistance to oxidative stress is a multigene trait in these strains. Both derived strains possess the same major-effect adaptations to oxidative stress, but have distinct modifiers of the phenotype. Similarly, both derived strains have altered their global transcriptional responses to oxidative stress in similar ways, but do have at least some distinct differences in transcriptional regulation. We conclude that short-term laboratory selections can generate complex genetic variation that may be a useful substrate for testing evolutionary theories.
Complex Signatures of Selection and Gene Conversion in the Duplicated Globin Genes of House Mice
Authors: Storz Jay F , Baze Monica , Waite Jessica L , Hoffmann Federico G , Opazo Juan C , Hayes Jack P
Published: July 2007

Results of electrophoretic surveys have suggested that hemoglobin polymorphism may be maintained by balancing selection in natural populations of house mice, Mus musculus. Here we report a survey of nucleotide variation in the adult globin genes of house mice from South America. We surveyed nucleotide polymorphism in two closely linked α-globin paralogs and two closely linked β-globin paralogs to test whether patterns of variation are consistent with a model of long-term balancing selection. Surprisingly high levels of nucleotide polymorphism at the two β-globin paralogs were attributable to the segregation of two highly divergent haplotypes, Hbbs (which carries two identical β-globin paralogs) and Hbbd (which carries two functionally divergent β-globin paralogs). Interparalog gene conversion on the Hbbs haplotype has produced a highly unusual situation in which the two paralogs are more similar to one another than either one is to its allelic counterpart on the Hbbd haplotype. Levels of nucleotide polymorphism and linkage disequilibrium at the two β-globin paralogs suggest a complex history of diversity-enhancing selection that may be responsible for long-term maintenance of alternative protein alleles. The alternative two-locus β-globin haplotypes are associated with pronounced differences in intraerythrocyte glutathione and nitric oxide metabolism, suggesting a possible mechanism for selection on hemoglobin function.
Toward a Systems Biology of Mouse Inner Ear Organogenesis: Gene Expression Pathways, Patterns and Network Analysis
Authors: Sajan Samin A , Warchol Mark E , Lovett Michael
Published: July 2007

We describe the most comprehensive study to date on gene expression during mouse inner ear (IE) organogenesis. Samples were microdissected from mouse embryos at E9–E15 in half-day intervals, a period that spans all of IE organogenesis. These included separate dissections of all discernible IE substructures such as the cochlea, utricle, and saccule. All samples were analyzed on high density expression microarrays under strict statistical filters. Extensive confirmatory tests were performed, including RNA in situ hybridizations. More than 5000 genes significantly varied in expression according to developmental stage, tissue, or both and defined 28 distinct expression patterns. For example, upregulation of 315 genes provided a clear-cut “signature” of early events in IE specification. Additional, clear-cut, gene expression signatures marked specific structures such as the cochlea, utricle, or saccule throughout late IE development. Pathway analysis identified 53 signaling cascades enriched within the 28 patterns. Many novel pathways, not previously implicated in IE development, including β-adrenergic, amyloid, estrogen receptor, circadian rhythm, and immune system pathways, were identified. Finally, we identified positional candidate genes in 54 uncloned nonsyndromic human deafness intervals. This detailed analysis provides many new insights into the spatial and temporal genetic specification of this complex organ system.
Evolutionary History and Positional Shift of a Rice Centromere
Authors: Ma Jianxin , Wing Rod A , Bennetzen Jeffrey L , Jackson Scott A
Published: July 2007

Rice centromere 8 was previously proposed to be an “immature” centromere that recently arose from a genic region. Our comparative genomics analysis indicates that Cen8 was formed at its current location at least 7–9 million years ago and was physically shifted by a more recent inversion of a segment spanning centromeric and pericentromeric regions.