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  • 1
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    Temperature-Related Reaction Norms of Gene Expression: Regulatory Architecture and Functional Implications (2015)
    Oxford University Press
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    Publication Date: 2015-08-20
    Description: The environment has profound effects on the expression of many traits and reaction norms describe the expression dynamics of a trait across a broad range of environmental conditions. Here, we analyze gene expression in Drosophila melanogaster across four different developmental temperatures (13–29 °C). Gene expression is highly plastic with 83.3% of the genes being differentially expressed. We distinguished three components of plasticity: 1) Dynamics of gene expression intensity (sum of change), 2) direction of change, and 3) curvature of the reaction norm (linear vs. quadratic). Studying their regulatory architecture we found that all three plasticity components were most strongly affected by the number of different transcription factors (TFs) binding to the target gene. More TFs were found in genes with less expression changes across temperatures. Although the effect of microRNAs was weaker, we consistently noted a trend in the opposite direction. The most plastic genes were regulated by fewer TFs and more microRNAs than less plastic genes. Different patterns of plasticity were also reflected by their functional characterization based on gene ontology. Our results suggest that reaction norms provide an important key to understand the functional requirements of natural populations exposed to variable environmental conditions.
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    Drosophila americana as a Model Species for Comparative Studies on the Molecular Basis of Phenotypic Variation (2013)
    Oxford University Press
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    Publication Date: 2013-04-08
    Description: Understanding the molecular basis of within and between species phenotypic variation is one of the main goals of Biology. In Drosophila , most of the work regarding this issue has been performed in D. melanogaster , but other distantly related species must also be studied to verify the generality of the findings obtained for this species. Here, we make the case for D. americana , a species of the virilis group of Drosophila that has been diverging from the model species, D. melanogaster , for approximately 40 Myr. To determine the suitability of this species for such studies, polymorphism and recombination estimates are presented for D. americana based on the largest nucleotide sequence polymorphism data set so far analyzed (more than 100 data sets) for this species. The polymorphism estimates are also compared with those obtained from the comparison of the genome assembly of two D. americana strains (H5 and W11) here reported. As an example of the general utility of these resources, we perform a preliminary study on the molecular basis of lifespan differences in D. americana . First, we show that there are lifespan differences between D. americana populations from different regions of the distribution range. Then, we perform five F2 association experiments using markers for 21 candidate genes previously identified in D. melanogaster . Significant associations are found between polymorphism at two genes ( hep and Lim3 ) and lifespan. For the F2 association study involving the two sequenced strains (H5 and W11), we identify amino acid differences at Lim3 and Hep that could be responsible for the observed changes in lifespan. For both genes, no large gene expression differences were observed between the two strains.
    Electronic ISSN: 1759-6653
    Topics: Biology
    Published by Oxford University Press
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  • 3
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    A discontinuous Galerkin method with a modified penalty flux for the propagation and scattering of acousto-elastic waves (2016)
    Oxford University Press
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    Publication Date: 2016-04-07
    Description: We develop an approach for simulating acousto-elastic wave phenomena, including scattering from fluid–solid boundaries, where the solid is allowed to be anisotropic, with the discontinuous Galerkin method. We use a coupled first-order elastic strain-velocity, acoustic velocity–pressure formulation, and append penalty terms based on interior boundary continuity conditions to the numerical (central) flux so that the consistency condition holds for the discretized discontinuous Galerkin weak formulation. We incorporate the fluid–solid boundaries through these penalty terms and obtain a stable algorithm. Our approach avoids the diagonalization into polarized wave constituents such as in the approach based on solving elementwise Riemann problems.
    Keywords: Seismology
    Print ISSN: 0956-540X
    Electronic ISSN: 1365-246X
    Topics: Geosciences
    Published by Oxford University Press on behalf of The Deutsche Geophysikalische Gesellschaft (DGG) and the Royal Astronomical Society (RAS).
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  • 4
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    Patterns of Linkage Disequilibrium and Long Range Hitchhiking in Evolving Experimental Drosophila melanogaster Populations (2015)
    Oxford University Press
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    Publication Date: 2015-01-20
    Description: Whole-genome resequencing of experimental populations evolving under a specific selection regime has become a popular approach to determine genotype–phenotype maps and understand adaptation to new environments. Despite its conceptual appeal and success in identifying some causative genes, it has become apparent that many studies suffer from an excess of candidate loci. Several explanations have been proposed for this phenomenon, but it is clear that information about the linkage structure during such experiments is needed. Until now only Pool-Seq (whole-genome sequencing of pools of individuals) data were available, which do not provide sufficient information about the correlation between linked sites. We address this problem in two complementary analyses of three replicate Drosophila melanogaster populations evolving to a new hot temperature environment for almost 70 generations. In the first analysis, we sequenced 58 haploid genomes from the founder population and evolved flies at generation 67. We show that during the experiment linkage disequilibrium (LD) increased almost uniformly over much greater distances than typically seen in Drosophila . In the second analysis, Pool-Seq time series data of the three replicates were combined with haplotype information from the founder population to follow blocks of initial haplotypes over time. We identified 17 selected haplotype-blocks that started at low frequencies in the base population and increased in frequency during the experiment. The size of these haplotype-blocks ranged from 0.082 to 4.01 Mb. Moreover, between 42% and 46% of the top candidate single nucleotide polymorphisms from the comparison of founder and evolved populations fell into the genomic region covered by the haplotype-blocks. We conclude that LD in such rising haplotype-blocks results in long range hitchhiking over multiple kilobase-sized regions. LD in such haplotype-blocks is therefore a major factor contributing to an excess of candidate loci. Although modifications of the experimental design may help to reduce the hitchhiking effect and allow for more precise mapping of causative variants, we also note that such haplotype-blocks might be well suited to study the dynamics of selected genomic regions during experimental evolution studies.
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
    Published by Oxford University Press
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  • 5
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    MapMyFlu: visualizing spatio-temporal relationships between related influenza sequences (2015)
    Oxford University Press
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    Publication Date: 2015-07-02
    Description: Understanding the molecular dynamics of viral spreading is crucial for anticipating the epidemiological implications of disease outbreaks. In the case of influenza, reassortments or point mutations affect the adaption to new hosts or resistance to anti-viral drugs and can determine whether a new strain will result in a pandemic infection or a less severe progression. To this end, tools integrating molecular information with epidemiological parameters are important to understand how molecular characteristics reflect in the infection dynamics. We present a new web tool, MapMyFlu, which allows to spatially and temporally display influenza viruses related to a query sequence on a Google Map based on BLAST results against the NCBI Influenza Database. Temporal and geographical trends appear clearly and may help in reconstructing the evolutionary history of a particular sequence. The tool is accessible through a web server, hence without the need for local installation. The website has an intuitive design and provides an easy-to-use service, and is available at http://mapmyflu.ipmb.uni-heidelberg.de
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 6
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    X-linked dystonia parkinsonism syndrome (XDP, lubag): disease-specific sequence change DSC3 in TAF1/DYT3 affects genes in vesicular transport and dopamine metabolism (2013)
    Oxford University Press
    Details
    Publication Date: 2013-02-02
    Description: X-chromosomal dystonia parkinsonism syndrome (XDP, ‘lubag’) is associated with sequence changes within the TAF1/DYT3 multiple transcript system. Although most sequence changes are intronic, one, disease-specific single-nucleotide change 3 (DSC3), is located within an exon (d4). Transcribed exon d4 occurs as part of multiple splice variants. These variants include exons d3 and d4 spliced to exons of TAF1 , and an independent transcript composed of exons d2–d4. Location of DSC3 in exon d4 and utilization of this exon in multiple splice variants suggest an important role of DSC3 in the XDP pathogenesis. To test this hypothesis, we transfected neuroblastoma cells with four expression constructs, including exons d2–d4 [d2–d4/wild-type (wt) and d2-d4/DSC3] and d3–d4 (d3–d4/wt and d3–d4/DSC3). Expression profiling revealed a dramatic effect of DSC3 on overall gene expression. Three hundred and sixty-two genes differed between cells containing d2–d4/wt and d2–d4/DSC3. Annotation clustering revealed enrichment of genes related to vesicular transport, dopamine metabolism, synapse function, Ca 2+ metabolism and oxidative stress. Two hundred and eleven genes were differentially expressed in d3–d4/wt versus d3–d4/DSC3. Annotation clustering highlighted genes in signal transduction and cell–cell interaction. The data show an important role of physiologically occurring transcript d2–d4 in normal brain function. Interference with this role by DSC3 is a likely pathological mechanism in XDP. Disturbance of dopamine function and of Ca 2+ metabolism can explain abnormal movement; loss of protection against reactive oxygen species may account for the neurodegenerative changes in XDP. Although d3–d4 also affect genes potentially related to neurodegenerative processes, their physiologic role as splice variants of TAF1 awaits further exploration.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 7
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    Genome-wide genetic homogeneity between sexes and populations for human height and body mass index (2015)
    Oxford University Press
    Details
    Publication Date: 2015-12-01
    Description: Sex-specific genetic effects have been proposed to be an important source of variation for human complex traits. Here we use two distinct genome-wide methods to estimate the autosomal genetic correlation ( r g ) between men and women for human height and body mass index (BMI), using individual-level ( n = ~44 000) and summary-level ( n = ~133 000) data from genome-wide association studies. Results are consistent and show that the between-sex genetic correlation is not significantly different from unity for both traits. In contrast, we find evidence of genetic heterogeneity between sexes for waist–hip ratio ( r g = ~0.7) and between populations for BMI ( r g = ~0.9 between Europe and the USA) but not for height. The lack of evidence for substantial genetic heterogeneity for body size is consistent with empirical findings across traits and species.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 8
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    Detecting Selective Sweeps from Pooled Next-Generation Sequencing Samples (2012)
    Oxford University Press
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    Publication Date: 2012-08-23
    Description: Due to its cost effectiveness, next-generation sequencing of pools of individuals (Pool-Seq) is becoming a popular strategy for characterizing variation in population samples. Because Pool-Seq provides genome-wide SNP frequency data, it is possible to use them for demographic inference and/or the identification of selective sweeps. Here, we introduce a statistical method that is designed to detect selective sweeps from pooled data by accounting for statistical challenges associated with Pool-Seq, namely sequencing errors and random sampling among chromosomes. This allows for an efficient use of the information: all base calls are included in the analysis, but the higher credibility of regions with higher coverage and base calls with better quality scores is accounted for. Computer simulations show that our method efficiently detects sweeps even at very low coverage (0.5 x per chromosome). Indeed, the power of detecting sweeps is similar to what we could expect from sequences of individual chromosomes. Since the inference of selective sweeps is based on the allele frequency spectrum (AFS), we also provide a method to accurately estimate the AFS provided that the quality scores for the sequence reads are reliable. Applying our approach to Pool-Seq data from Drosophila melanogaster , we identify several selective sweep signatures on chromosome X that include some previously well-characterized sweeps like the wapl region.
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
    Published by Oxford University Press
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  • 9
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    Massive Habitat-Specific Genomic Response in D. melanogaster Populations during Experimental Evolution in Hot and Cold Environments (2014)
    Oxford University Press
    Details
    Publication Date: 2014-01-23
    Description: Experimental evolution in combination with whole-genome sequencing (evolve and resequence [E&R]) is a promising approach to define the genotype–phenotype map and to understand adaptation in evolving populations. Many previous studies have identified a large number of putative selected sites (i.e., candidate loci), but it remains unclear to what extent these loci are genuine targets of selection or experimental noise. To address this question, we exposed the same founder population to two different selection regimes—a hot environment and a cold environment—and quantified the genomic response in each. We detected large numbers of putative selected loci in both environments, albeit with little overlap between the two sets of candidates, indicating that most resulted from habitat-specific selection. By quantifying changes across multiple independent biological replicates, we demonstrate that most of the candidate SNPs were false positives that were linked to selected sites over distances much larger than the typical linkage disequilibrium range of Drosophila melanogaster . We show that many of these mid- to long-range associations were attributable to large segregating inversions and confirm by computer simulations that such patterns could be readily replicated when strong selection acts on rare haplotypes. In light of our findings, we outline recommendations to improve the performance of future Drosophila E&R studies which include using species with negligible inversion loads, such as D. mauritiana and D. simulans , instead of D. melanogaster .
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
    Published by Oxford University Press
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  • 10
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    Optimisation of implementation policies of environmental quota trade (2011)
    Oxford University Press
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    Publication Date: 2011-12-27
    Description: This paper analyses implementation policies of environmental quota trade, with the Flemish nutrient production rights as an example. Implementation policies concern the transaction quantity, quota reduction and prevention of speculation. They are analysed with a static and a dynamic multi-agent quota trade model. The static model with discrete non-auctioned quota trade shows that the obligation for quota sellers to entirely stop their production stimulates structural change. The dynamic model version indicates that a flat rate reduction on traded quota and measures taken to prevent speculation combined with too low penalties for overuse stimulate the total production.
    Keywords: Q12 - Micro Analysis of Farm Firms, Farm Households, and Farm Input Markets, Q15 - Land Ownership and Tenure ; Land Reform ; Land Use ; Irrigation, Q18 - Agricultural Policy ; Food Policy
    Print ISSN: 0165-1587
    Electronic ISSN: 1464-3618
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
    Published by Oxford University Press
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