Beschreibung: The budding yeast Saccharomyces cerevisiae is important for human food production and as a model organism for biological research. The genetic diversity contained in the global population of yeast strains represents a valuable resource for a number of fields, including genetics, bioengineering, and studies of evolution and population structure. Here, we apply a multiplexed, reduced genome sequencing strategy (restriction site–associated sequencing or RAD-seq) to genotype a large collection of S. cerevisiae strains isolated from a wide range of geographical locations and environmental niches. The method permits the sequencing of the same 1% of all genomes, producing a multiple sequence alignment of 116,880 bases across 262 strains. We find diversity among these strains is principally organized by geography, with European, North American, Asian, and African/S. E. Asian populations defining the major axes of genetic variation. At a finer scale, small groups of strains from cacao, olives, and sake are defined by unique variants not present in other strains. One population, containing strains from a variety of fermentations, exhibits high levels of heterozygosity and a mixture of alleles from European and Asian populations, indicating an admixed origin for this group. We propose a model of geographic differentiation followed by human-associated admixture, primarily between European and Asian populations and more recently between European and North American populations. The large collection of genotyped yeast strains characterized here will provide a useful resource for the broad community of yeast researchers.

Beschreibung: The signal transducer and activator of transcription 3 (STAT3) is a transcription factor that, when dysregulated, becomes a powerful oncogene found in many human cancers, including diffuse large B-cell lymphoma. Diffuse large B-cell lymphoma is the most common form of non-Hodgkin’s lymphoma and has two major subtypes: germinal center B-cell–like and activated B–cell—like. Compared with the germinal center B-cell–like form, activated B-cell–like lymphomas respond much more poorly to current therapies and often exhibit overexpression or overactivation of STAT3. To investigate how STAT3 might contribute to this aggressive phenotype, we have integrated genome-wide studies of STAT3 DNA binding using chromatin immunoprecipitation-sequencing with whole-transcriptome profiling using RNA-sequencing. STAT3 binding sites are present near almost a third of all genes that differ in expression between the two subtypes, and examination of the affected genes identified previously undetected and clinically significant pathways downstream of STAT3 that drive oncogenesis. Novel treatments aimed at these pathways may increase the survivability of activated B-cell–like diffuse large B-cell lymphoma.

Beschreibung: Drosophila suzukii Matsumura (spotted wing drosophila) has recently become a serious pest of a wide variety of fruit crops in the United States as well as in Europe, leading to substantial yearly crop losses. To enable basic and applied research of this important pest, we sequenced the D. suzukii genome to obtain a high-quality reference sequence. Here, we discuss the basic properties of the genome and transcriptome and describe patterns of genome evolution in D. suzukii and its close relatives. Our analyses and genome annotations are presented in a web portal, SpottedWingFlyBase, to facilitate public access.

Beschreibung: In crop breeding, the interest of predicting the performance of candidate cultivars in the field has increased due to recent advances in molecular breeding technologies. However, the complexity of the wheat genome presents some challenges for applying new technologies in molecular marker identification with next-generation sequencing. We applied genotyping-by-sequencing, a recently developed method to identify single-nucleotide polymorphisms, in the genomes of 384 wheat ( Triticum aestivum ) genotypes that were field tested under three different water regimes in Mediterranean climatic conditions: rain-fed only, mild water stress, and fully irrigated. We identified 102,324 single-nucleotide polymorphisms in these genotypes, and the phenotypic data were used to train and test genomic selection models intended to predict yield, thousand-kernel weight, number of kernels per spike, and heading date. Phenotypic data showed marked spatial variation. Therefore, different models were tested to correct the trends observed in the field. A mixed-model using moving-means as a covariate was found to best fit the data. When we applied the genomic selection models, the accuracy of predicted traits increased with spatial adjustment. Multiple genomic selection models were tested, and a Gaussian kernel model was determined to give the highest accuracy. The best predictions between environments were obtained when data from different years were used to train the model. Our results confirm that genotyping-by-sequencing is an effective tool to obtain genome-wide information for crops with complex genomes, that these data are efficient for predicting traits, and that correction of spatial variation is a crucial ingredient to increase prediction accuracy in genomic selection models.

Beschreibung: Recently, in 2013 Feder et al. proposed the frequency increment test (FIT), which evaluates natural selection at a single diallelic locus by the use of time-series data of allele frequencies. This test is unbiased under conditions of constant population size and no sampling noise. Here, we expand upon the FIT by introducing a test that explicitly allows for changes in population size by using information from independent reference loci. Various demographic models suggest that our proposed test is unbiased irrespective of fluctuations in population size when sampling noise can be ignored and that it has greater power to detect selection than the FIT if sufficient reference loci are used.

Beschreibung: The relationships between reproduction and aging are important for understanding the mechanisms of aging and evaluating evolutionary theories of aging. To investigate the effects of progeny production on reproductive and somatic aging, we conducted longitudinal studies of Caenorhabditis elegans hermaphrodites. For mated wild-type animals that were not sperm limited and survived past the end of the reproductive period, high levels of cross-progeny production were positively correlated with delayed reproductive and somatic aging. In this group of animals, individuals that generated more cross progeny also reproduced and lived longer than individuals that generated fewer cross progeny. These results indicate that progeny production does not accelerate reproductive or somatic aging. This longitudinal study demonstrated that cumulative cross progeny production through day four is an early-stage biomarker that is a positive predictor of longevity. Furthermore, in mated animals, high levels of early cross progeny production were positively correlated with high levels of late cross progeny production, indicating that early progeny production does not accelerate reproductive aging. The relationships between progeny production and aging were further evaluated by comparing self-fertile hermaphrodites that generated relatively few self progeny with mated hermaphrodites that generated many cross progeny. The timing of age-related somatic degeneration was similar in these groups, suggesting progeny production does not accelerate somatic aging. These studies rigorously define relationships between progeny production, reproductive aging, and somatic aging and identify new biomarkers of C. elegans aging. These results indicate that some mechanisms or pathways control age-related degeneration of both reproductive and somatic tissues in C. elegans .

Beschreibung: The Chinook salmon genetic linkage groups have been assigned to specific chromosomes using fluorescence in situ hybridization with bacterial artificial chromosome probes containing genetic markers mapped to each linkage group in Chinook salmon and rainbow trout. Comparison of the Chinook salmon chromosome map with that of rainbow trout provides strong evidence for conservation of large syntenic blocks in these species, corresponding to entire chromosome arms in the rainbow trout as expected. In almost every case, the markers were found at approximately the same location on the chromosome arm in each species, suggesting conservation of marker order on the chromosome arms of the two species in most cases. Although theoretically a few centric fissions could convert the karyotype of rainbow trout (2N = 58–64) into that of Chinook salmon (2N = 68) or vice versa , our data suggest that chromosome arms underwent multiple centric fissions and subsequent new centric fusions to form the current karyotypes. The morphology of only approximately one-third of the chromosome pairs have been conserved between the two species.

Beschreibung: By studying genomic changes over time in populations subjected to strong artificial directional selection, we can gain insights to the dynamics of beneficial alleles originating from the founder population or emerging as novel mutations undergoing ongoing selection. The Virginia lines are a chicken resource population generated by long-term bi-directional, single-trait selection for juvenile body weight. We studied genome-wide allele frequency changes from generation 40 to 53 using genome-wide genotypes from directional and relaxed selection lines. Overall, there were small changes in allele frequencies at individual loci over the studied time period; but, on average, the changes were greater in lines with larger phenotypic changes. This is consistent with previous findings that much of the response to selection over the first 40 years of selection was attributable to utilization of standing genetic variation at many loci in the genome, indicating a mostly polygenic architecture for body weight. Over the course of the selection experiment, the largest phenotypic response to selection was observed in the high-weight selected line, and in this line we detected a single locus where the allele frequency changed rapidly during a late stage of the experiment. This locus likely contains a novel, beneficial mutation that appeared between generations 40 and 45 and was driven to fixation in 5 to 10 generations. This result illustrates the dependence of continued long-term selection response on standing genetic variation at many loci as well as strong, novel, beneficial mutations.

Beschreibung: Expression levels of genes vary not only between different environmental conditions ("plasticity") but also between genetically identical cells in constant environment ("noise"). Intriguingly, these two measures of gene expression variability correlate positively with each other in yeast. This coupling was found to be particularly strong for genes with specific promoter architecture (TATA box and high nucleosome occupancy) but weak for genes in which high noise may be detrimental ( e.g. , essential genes), suggesting that noise–plasticity coupling is an evolvable trait in yeast and may constrain evolution of gene expression and promoter usage. Recently, similar genome-wide data on noise and plasticity have become available for Escherichia coli , providing the opportunity to study noise–plasticity correlation and its mechanism in a prokaryote, which follows a fundamentally different mode of transcription regulation than a eukaryote such as yeast. Using these data, I found significant positive correlation between noise and plasticity in E. coli . Furthermore, this coupling was highly influenced by the following: level of expression; essentiality and dosage sensitivity of genes; regulation by specific nucleoid-associated proteins, transcription factors, and sigma factors; and involvement in stress response. Many of these features are analogous to those found to influence noise–plasticity coupling in yeast. These results not only show the generality of noise–plasticity coupling across phylogenetically distant organisms but also suggest that its mechanism may be similar.

Beschreibung: Silene latifolia is a dioecious plant with heteromorphic XY sex chromosomes. Previous studies of sex chromosome–linked genes have suggested a gradual divergence between the X-linked and the Y-linked genes in proportion to the distance from the pseudoautosomal region. However, such a comparison has yet to be made for the noncoding regions. To better characterize the nonrecombining region of the X and Y chromosomes, we sequenced bacterial artificial chromosome clones containing the sex chromosome–linked paralogs SlAP3X and SlAP3Y , including 115 kb and 73 kb of sequences, respectively, flanking these genes. The synonymous nucleotide divergence between SlAP3X and SlAP3Y indicated that recombination stopped approximately 3.4 million years ago. Sequence homology analysis revealed the presence of six long terminal repeat retrotransposon-like elements. Using the nucleotide divergence calculated between left and right long terminal repeat sequences, insertion dates were estimated to be 0.083–1.6 million years ago, implying that all elements detected were inserted after recombination stopped. A reciprocal sequence homology search facilitated the identification of four homologous noncoding DNA regions between the X and Y chromosomes, spanning 6.7% and 10.6% of the X chromosome–derived and Y chromosome–derived sequences, respectively, investigated. Genomic Southern blotting and fluorescence in situ hybridization showed that the noncoding DNA flanking SlAP3X/Y has homology to many regions throughout the genome, regardless of whether they were homologous between the X and Y chromosomes. This finding suggests that most noncoding DNA regions rapidly lose their counterparts because of the introduction of transposable elements and indels (insertion–deletions) after recombination has stopped.