Felix Ott

Publications of Felix Ott

• Natural variation in biogenesis efficiency of individual Arabidopsis thaliana microRNAs.

  Authors: Marco Todesco, Sureshkumar Balasubramanian, Jun Cao, Felix Ott, Sridevi Sureshkumar, Korbinian Schneeberger, Rhonda Christiane Meyer, Thomas Altmann, Detlef Weigel

  Current biology : CB. 12/2011; 22(2):166-70.

  Like protein-coding genes, loci that produce microRNAs (miRNAs) are generally considered to be under purifying selection, consistent with miRNA polymorphisms being able to cause disease.Like protein-coding genes, loci that produce microRNAs (miRNAs) are generally considered to be under purifying selection, consistent with miRNA polymorphisms being able to cause disease. Nevertheless, it has been hypothesized that variation in miRNA genes may contribute to phenotypic diversity. Here we demonstrate that a naturally occurring polymorphism in the MIR164A gene affects leaf shape and shoot architecture in Arabidopsis thaliana, with the effects being modified by additional loci in the genome. A single base pair substitution in the miRNA complementary sequence alters the predicted stability of the miRNA:miRNA(∗) duplex. It thereby greatly reduces miRNA accumulation, probably because it interferes with precursor processing. We demonstrate that this is not a rare exception and that natural strains of Arabidopsis thaliana harbor dozens of similar polymorphisms that affect processing of a wide range of miRNA precursors. Our results suggest that natural variation in miRNA biogenesis resulting from cis mutations is a common contributor to phenotypic variation in plants.

• Whole-genome sequencing of multiple Arabidopsis thaliana populations.

  Authors: Jun Cao, Korbinian Schneeberger, Stephan Ossowski, Torsten Günther, Sebastian Bender, Joffrey Fitz, Daniel Koenig, Christa Lanz, Oliver Stegle, Christoph Lippert, Xi Wang, Felix Ott, Jonas Müller, Carlos Alonso-Blanco, Karsten Borgwardt, Karl J Schmid, Detlef Weigel

  Nature genetics. 08/2011; 43(10):956-63.

  The plant Arabidopsis thaliana occurs naturally in many different habitats throughout Eurasia. As a foundation for identifying genetic variation contributing to adaptation to diverse environments, aThe plant Arabidopsis thaliana occurs naturally in many different habitats throughout Eurasia. As a foundation for identifying genetic variation contributing to adaptation to diverse environments, a 1001 Genomes Project to sequence geographically diverse A. thaliana strains has been initiated. Here we present the first phase of this project, based on population-scale sequencing of 80 strains drawn from eight regions throughout the species' native range. We describe the majority of common small-scale polymorphisms as well as many larger insertions and deletions in the A. thaliana pan-genome, their effects on gene function, and the patterns of local and global linkage among these variants. The action of processes other than spontaneous mutation is identified by comparing the spectrum of mutations that have accumulated since A. thaliana diverged from its closest relative 10 million years ago with the spectrum observed in the laboratory. Recent species-wide selective sweeps are rare, and potentially deleterious mutations are more common in marginal populations.

• Reference-guided assembly of four diverse Arabidopsis thaliana genomes.

  Authors: Korbinian Schneeberger, Stephan Ossowski, Felix Ott, Juliane D Klein, Xi Wang, Christa Lanz, Lisa M Smith, Jun Cao, Joffrey Fitz, Norman Warthmann, Stefan R Henz, Daniel H Huson, Detlef Weigel

  Proceedings of the National Academy of Sciences of the United States of America. 06/2011; 108(25):10249-54.

  We present whole-genome assemblies of four divergent Arabidopsis thaliana strains that complement the 125-Mb reference genome sequence released a decade ago. Using a newly developed reference-guidedWe present whole-genome assemblies of four divergent Arabidopsis thaliana strains that complement the 125-Mb reference genome sequence released a decade ago. Using a newly developed reference-guided approach, we assembled large contigs from 9 to 42 Gb of Illumina short-read data from the Landsberg erecta (Ler-1), C24, Bur-0, and Kro-0 strains, which have been sequenced as part of the 1,001 Genomes Project for this species. Using alignments against the reference sequence, we first reduced the complexity of the de novo assembly and later integrated reads without similarity to the reference sequence. As an example, half of the noncentromeric C24 genome was covered by scaffolds that are longer than 260 kb, with a maximum of 2.2 Mb. Moreover, over 96% of the reference genome was covered by the reference-guided assembly, compared with only 87% with a complete de novo assembly. Comparisons with 2 Mb of dideoxy sequence reveal that the per-base error rate of the reference-guided assemblies was below 1 in 10,000. Our assemblies provide a detailed, genomewide picture of large-scale differences between A. thaliana individuals, most of which are difficult to access with alignment-consensus methods only. We demonstrate their practical relevance in studying the expression differences of polymorphic genes and show how the analysis of sRNA sequencing data can lead to erroneous conclusions if aligned against the reference genome alone. Genome assemblies, raw reads, and further information are accessible through http://1001genomes.org/projects/assemblies.html.

• Prediction of regulatory interactions from genome sequences using a biophysical model for the Arabidopsis LEAFY transcription factor.

  Authors: Edwige Moyroud, Eugenio Gómez Minguet, Felix Ott, Levi Yant, David Posé, Marie Monniaux, Sandrine Blanchet, Olivier Bastien, Emmanuel Thévenon, Detlef Weigel, Markus Schmid, François Parcy

  The Plant cell. 04/2011; 23(4):1293-306.

  Despite great advances in sequencing technologies, generating functional information for nonmodel organisms remains a challenge. One solution lies in an improved ability to predict genetic circuitsDespite great advances in sequencing technologies, generating functional information for nonmodel organisms remains a challenge. One solution lies in an improved ability to predict genetic circuits based on primary DNA sequence in combination with detailed knowledge of regulatory proteins that have been characterized in model species. Here, we focus on the LEAFY (LFY) transcription factor, a conserved master regulator of floral development. Starting with biochemical and structural information, we built a biophysical model describing LFY DNA binding specificity in vitro that accurately predicts in vivo LFY binding sites in the Arabidopsis thaliana genome. Applying the model to other plant species, we could follow the evolution of the regulatory relationship between LFY and the AGAMOUS (AG) subfamily of MADS box genes and show that this link predates the divergence between monocots and eudicots. Remarkably, our model succeeds in detecting the connection between LFY and AG homologs despite extensive variation in binding sites. This demonstrates that the cis-element fluidity recently observed in animals also exists in plants, but the challenges it poses can be overcome with predictions grounded in a biophysical model. Therefore, our work opens new avenues to deduce the structure of regulatory networks from mere inspection of genomic sequences.

• Transposable elements and small RNAs contribute to gene expression divergence between Arabidopsis thaliana and Arabidopsis lyrata.

  Authors: Jesse D Hollister, Lisa M Smith, Ya-Long Guo, Felix Ott, Detlef Weigel, Brandon S Gaut

  Proceedings of the National Academy of Sciences of the United States of America. 02/2011; 108(6):2322-7.

  Transposable elements (TEs) are often the primary determinant of genome size differences among eukaryotes. In plants, the proliferation of TEs is countered through epigenetic silencing mechanismsTransposable elements (TEs) are often the primary determinant of genome size differences among eukaryotes. In plants, the proliferation of TEs is countered through epigenetic silencing mechanisms that prevent mobility. Recent studies using the model plant Arabidopsis thaliana have revealed that methylated TE insertions are often associated with reduced expression of nearby genes, and these insertions may be subject to purifying selection due to this effect. Less is known about the genome-wide patterns of epigenetic silencing of TEs in other plant species. Here, we compare the 24-nt siRNA complement from A. thaliana and a closely related congener with a two- to threefold higher TE copy number, Arabidopsis lyrata. We show that TEs--particularly siRNA-targeted TEs--are associated with reduced gene expression within both species and also with gene expression differences between orthologs. In addition, A. lyrata TEs are targeted by a lower fraction of uniquely matching siRNAs, which are associated with more effective silencing of TE expression. Our results suggest that the efficacy of RNA-directed DNA methylation silencing is lower in A. lyrata, a finding that may shed light on the causes of differential TE proliferation among species.

• Comparative analysis of non-autonomous effects of tasiRNAs and miRNAs in Arabidopsis thaliana.

  Authors: Felipe Fenselau de Felippes, Felix Ott, Detlef Weigel

  Nucleic acids research. 12/2010; 39(7):2880-9.

  In plants, small interfering RNAs (siRNAs) can trigger a silencing signal that may spread within a tissue to adjacent cells or even systemically to other organs. Movement of the signal is initiallyIn plants, small interfering RNAs (siRNAs) can trigger a silencing signal that may spread within a tissue to adjacent cells or even systemically to other organs. Movement of the signal is initially limited to a few cells, but in some cases the signal can be amplified and travel over larger distances. How far silencing initiated by other classes of plant small RNAs (sRNAs) than siRNAs can extend has been less clear. Using a system based on the silencing of the CH42 gene, we have tracked the mobility of silencing signals initiated in phloem companion cells by artificial microRNAs (miRNA) and trans-acting siRNA (tasiRNA) that have the same primary sequence. In this system, both the ta-siRNA and the miRNA act at a distance. Non-autonomous effects of the miRNA can be triggered by several different miRNA precursors deployed as backbones. While the tasiRNA also acts non-autonomously, it has a much greater range than the miRNA or hairpin-derived siRNAs directed against CH42, indicating that biogenesis can determine the non-autonomous effects of sRNAs. In agreement with this hypothesis, the silencing signals initiated by different sRNAs differ in their genetic requirements.

• Orchestration of the floral transition and floral development in Arabidopsis by the bifunctional transcription factor APETALA2.

  Authors: Levi Yant, Johannes Mathieu, Thanh Theresa Dinh, Felix Ott, Christa Lanz, Heike Wollmann, Xuemei Chen, Markus Schmid

  The Plant cell. 07/2010; 22(7):2156-70.

  The Arabidopsis thaliana transcription factor APETALA2 (AP2) has numerous functions, including roles in seed development, stem cell maintenance, and specification of floral organ identity. ToThe Arabidopsis thaliana transcription factor APETALA2 (AP2) has numerous functions, including roles in seed development, stem cell maintenance, and specification of floral organ identity. To understand the relationship between these different roles, we mapped direct targets of AP2 on a genome-wide scale in two tissue types. We find that AP2 binds to thousands of loci in the developing flower, many of which exhibit AP2-dependent transcription. Opposing, logical effects are evident in AP2 binding to two microRNA genes that influence AP2 expression, with AP2 positively regulating miR156 and negatively regulating miR172, forming a complex direct feedback loop, which also included all but one of the AP2-like miR172 target clade members. We compare the genome-wide direct target repertoire of AP2 with that of SCHLAFMUTZE, a closely related transcription factor that also represses the transition to flowering. We detect clear similarities and important differences in the direct target repertoires that are also tissue specific. Finally, using an inducible expression system, we demonstrate that AP2 has dual molecular roles. It functions as both a transcriptional activator and repressor, directly inducing the expression of the floral repressor AGAMOUS-LIKE15 and directly repressing the transcription of floral activators like SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1.

• MetaSim: a sequencing simulator for genomics and metagenomics.

  Authors: Daniel C Richter, Felix Ott, Alexander F Auch, Ramona Schmid, Daniel H Huson

  PLoS ONE. 02/2008; 3(10):e3373.

  BACKGROUND: The new research field of metagenomics is providing exciting insights into various, previously unclassified ecological systems. Next-generation sequencing technologies are producing aBACKGROUND: The new research field of metagenomics is providing exciting insights into various, previously unclassified ecological systems. Next-generation sequencing technologies are producing a rapid increase of environmental data in public databases. There is great need for specialized software solutions and statistical methods for dealing with complex metagenome data sets. METHODOLOGY/PRINCIPAL FINDINGS: To facilitate the development and improvement of metagenomic tools and the planning of metagenomic projects, we introduce a sequencing simulator called MetaSim. Our software can be used to generate collections of synthetic reads that reflect the diverse taxonomical composition of typical metagenome data sets. Based on a database of given genomes, the program allows the user to design a metagenome by specifying the number of genomes present at different levels of the NCBI taxonomy, and then to collect reads from the metagenome using a simulation of a number of different sequencing technologies. A population sampler optionally produces evolved sequences based on source genomes and a given evolutionary tree. CONCLUSIONS/SIGNIFICANCE: MetaSim allows the user to simulate individual read datasets that can be used as standardized test scenarios for planning sequencing projects or for benchmarking metagenomic software.