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Introduction
Additional affiliations
August 2014 - present
May 2011 - July 2014
February 2010 - present
Publications
Publications (144)
Compensating substitutions happen when one mutation is advantageously selected because it restores the loss of fitness induced by a previous deleterious mutation. How frequent such mutations occur in evolution and what is the structural and functional context permitting their emergence remain open questions. We built an atlas of intra-protein compe...
Compensating substitutions happen when one mutation is advantageously selected because it restores the loss of fitness induced by a previous deleterious mutation. How frequent such mutations occur in evolution and what is the structural and functional context permitting their emergence remain open questions. We built an atlas of intra-protein compe...
What shapes the distribution of nucleotide diversity along the genome? Attempts to answer this question have sparked debate about the roles of neutral stochastic processes and natural selection in molecular evolution. However, the mechanisms of evolution do not act in isolation, and integrative models that simultaneously consider the influence of m...
Understanding the dynamics of species adaptation to their environments has long been a central focus of the study of evolution. Theories of adaptation propose that populations evolve by "walking" in a fitness landscape. This "adaptive walk" is characterised by a pattern of diminishing returns, where populations further away from their fitness optim...
The tight interaction between pathogens and their hosts results in reciprocal selective forces that impact the genetic diversity of the interacting species. The footprints of this selection differ between pathosystems because of distinct life-history traits, demographic histories, or genome architectures. Here, we studied the genome-wide patterns o...
The tight interaction between pathogens and their hosts results in reciprocal selective forces that impact the genetic diversity of the interacting species. The footprints of this selection differ between pathosystems because of distinct life-history traits, demographic histories, or genome architectures. Here, we studied the genome-wide patterns o...
The development of coalescent theory paved the way to statistical inference from population genetic data. In the genomic era, however, coalescent models are limited due to the complexity of the underlying ancestral recombination graph. The sequentially Markov coalescent (SMC) is a heuristic that enables the modelling of complete genomes under the c...
Homing endonucleases (HE) are enzymes capable of cutting DNA at highly specific target sequences, the repair of the generated double‐strand break resulting in the insertion of the HE‐encoding gene (“homing” mechanism). HEs are present in all three domains of life and viruses; in eukaryotes, they are mostly found in the genomes of mitochondria and c...
The importance of adaptive mutations in molecular evolution is extensively debated. Recent developments in population genomics allow inferring rates of adaptive mutations by fitting a distribution of fitness effects to the observed patterns of polymorphism and divergence at sites under selection and sites assumed to evolve neutrally. Here, we summa...
Comparative genome analyses of eukaryotic pathogens including fungi and oomycetes have revealed extensive variability in genome composition and structure. The genomes of individuals from the same population can exhibit different numbers of chromosomes and different organization of chromosomal segments, defining so-called accessory compartments that...
As the number of available genome sequences from both closely related species and individuals within species increased, theoretical and methodological convergences between the fields of phylogenomics and population genomics emerged. Population genomics typically focuses on the analysis of variants, while phylogenomics heavily relies on genome align...
Population genomics is a growing field stemming from soon a 100 years of developments in population genetics. Here, we summarize the main concepts and terminology underlying both theoretical and empirical statistical population genomics studies. We provide the reader with pointers toward the original literature as well as methodological and histori...
This open access volume presents state-of-the-art inference methods in population genomics, focusing on data analysis based on rigorous statistical techniques. After introducing general concepts related to the biology of genomes and their evolution, the book covers state-of-the-art methods for the analysis of genomes in populations, including demog...
Chapter 2, “Processing and Analyzing Multiple Genomes Alignments with MafFilter,” was previously published without including the Electronic Supplementary Material. This has now been included in the revised version of this book.
Understanding the causes and consequences of recombination landscape evolution is a fundamental goal in genetics that requires recombination maps from across the tree of life. Such maps can be obtained from population genomic datasets, but require large sample sizes. Alternative methods are therefore necessary to research organisms where such datas...
Homing endonucleases (HE) are enzymes capable of excising their encoding gene and inserting it in a highly specific target sequence. As such, they act both as intronic sequences (type-I introns) and selfish invasive elements. HEs are present in all three kingdoms of life and viruses; in eukaryotes, they are mostly found in the genomes of mitochondr...
Borrowing both from population genetics and phylogenetics, the field of population genomics emerged as full genomes of several closely related species were available. Providing we can properly model sequence evolution within populations undergoing speciation events, this resource enables us to estimate key population genetics parameters such as anc...
Adaptive mutations play an important role in molecular evolution. However, the frequency and nature of these mutations at the intra-molecular level is poorly understood. To address this, we analysed the impact of protein architecture on the rate of adaptive substitutions, aiming to understand how protein biophysics influences fitness and adaptation...
Unravelling the strength, frequency, and distribution of selective variants along the genome as well as the underlying factors shaping this distribution are fundamental goals of evolutionary biology. Antagonistic host‐pathogen coevolution is thought to be a major driver of genome evolution between interacting species. While rapid evolution of patho...
Adaptive mutations play an important role in molecular evolution. However, the frequency and nature of these mutations at the intra-molecular level is poorly understood. To address this, we analysed the impact of protein architecture on the rate of adaptive substitutions, aiming to understand how protein biophysics influences fitness and adaptation...
Understanding the causes and consequences of recombination rate evolution is a fundamental goal in genetics that requires recombination maps from across the tree of life. Since statistical inference of recombination maps typically depends on large samples, reaching out studies to non-model organisms requires alternative tools. Here we extend the se...
Antagonistic host-pathogen co-evolution is a determining factor in the outcome of infection and shapes genetic diversity at the population level of both partners. Little is known about the overall genomic rate of evolution in pathogens or the molecular bases of rapid adaptation. Here we apply a population genomic approach to infer genome-wide patte...
Plants and fungi display a broad range of interactions in natural and agricultural ecosystems ranging from symbiosis to parasitism. These ecological interactions result in coevolution between genes belonging to different partners. A well-understood example are secreted fungal effector proteins and their host targets, which play an important role in...
Meiotic recombination is an important driver of evolution. Variability in the intensity of recombination across chromosomes can affect sequence composition, nucleotide variation and rates of adaptation. In many organisms recombination events are concentrated within short segments termed recombination hotspots. The variation in recombination rate an...
Plants and fungi display a broad range of interactions in natural and agricultural ecosystems ranging from symbiosis to parasitism. These ecological interactions result in coevolution between genes belonging to different partners. A well-understood example are secreted fungal effector proteins and their host targets, which play an important role in...
Meiotic recombination is an important driver of evolution. Variability in the intensity of recombination across chromosomes can affect sequence composition, nucleotide variation and rates of adaptation. In many organisms recombination events are concentrated within short segments termed recombination hotspots. The variation in recombination rate an...
Gene expression is a noisy process: in constant environment and genotype, cell to cell variability occurs because of randomness of biochemical reactions...
Biochemical reactions within individual cells result from the interactions of molecules, typically in small numbers. Consequently, the inherent stochasticity of binding and diffusion processes g...
Because biochemical processes within individual cells involve a small number of molecules, they are subject to random fluctuations. As a result, isogenic cell populations show different concentrations of the same mRNA and protein, even in homogeneous conditions. The extent and consequences of this stochastic gene expression have only recently been...
With the advent of sequencing techniques population genomics took a major shift. The structure of data sets has evolved from a sample of a few loci in the genome, sequenced in dozens of individuals, to collections of complete genomes, virtually comprising all available loci. Initially sequenced in a few individuals, such genomic data sets are now r...
The biotrophic basidiomycete fungus Ustilago maydis causes smut disease in maize. Hallmarks of the disease are large tumors that develop on all aerial parts of the host in which dark pigmented teliospores are formed. We have identified a member of the WOPR family of transcription factors, Ros1, as major regulator of spore formation in U. maydis. ro...
Ros1 belongs to the WOPR family of transcriptional regulators.
(A) Schematic representation of the domain structure of U. maydis Ros1 protein (UmRos1, XP_011392215) and other members of the WOPR family including all WOPR proteins which have been experimentally characterized: Zymoseptoria tritici Wor1 (ZmWor1, AHH91582), Cladosporium fulvum Wor1 (Cf...
Virulence of mutants lacking either UMAG_02775 or UMAG_01390.
Wild type strains FB1 and FB2 and the corresponding UMAG_02775 and UMAG_01390 deletion and complementation strains were mixed in the indicated combinations and injected into maize seedlings. Disease symptoms were scored 12 days after infection according to Kämper et al. (2006) [10]. Colo...
List of potential direct Ros1 targets in U. maydis.
(XLSX)
Occurence of motifs related to the Wor1 binding site in the ChIP peak sequences.
(XLSX)
In vitro binding of Ros1WOPR-His to several target promoters identified by ChIP.
Ros1WOPR-His expressed and purified from E. coli was used in EMSA assays with probes corresponding to target sequences identified by ChIP in the promoters of the transcription factor gene UMAG_02775 (A), the downregulated effector genes UMAG_02854, UMAG_04040, UMAG_025...
ros1 mutants are able to mate and filament.
Strains FB1, FB2, FB1Δros1 and FB2Δros1 were grown in YEPSL to an OD600 of 1.0, washed and resuspended in water. The strains indicated on top were spotted alone and in combinations with the strains indicated on the left side on charcoal-containing PD plates and incubated at room temperature for 48h. White...
Ros1 is involved in the regulation of rum1, ust1 and hgl1.
qRT-PCR analysis of rum1, ust1, hgl1 and tup1 expression during plant infection by the wild type strains FB1 x FB2 or the corresponding ros1 deletion strains. Infected plant samples were collected at the time-points indicated below. qRT-PCR analysis was performed using the constitutively ex...
ros1-dependently regulated U. maydis genes 8 days after infection determined by RNA-seq.
(XLSX)
Validation of putative Ros1 targets identified by RNA-seq results through RT-qPCR.
The expression of genes encoding glycoside hydrolases (UMAG_05550, UMAG_04503), a trehalase: (UMAG_02212), a cyclopropane fatty acid synthase (UMAG_01070), a polyketide synthase (pks1), transcription factors (UMAG_04101, biz1, rbf1, fox1, UMAG_02775) and secreted eff...
Ros1 induces the expression of the transcription factor genes UMAG_01390 and UMAG_02775 late during infection.
qRT-PCR analysis of UMAG_02775 and UMAG_01390 expression during plant infection by the wild type strains FB1 x FB2 (grey bars) or the corresponding ros1 deletion strains (white bars). Infected plant samples were collected at the time-point...
List of genomic regions bound by Ros1 determined by ChIP-seq analysis.
(XLSX)
U. maydis strain list.
(DOCX)
Motivation:
In many organisms, including humans, recombination clusters within recombination hotspots. The standard method for de novo detection of recombinants at hotspots is sperm typing. This relies on allele-specific PCR at single nucleotide polymorphisms. Designing allele-specific primers by hand is time-consuming. We have therefore written a...
Smut fungi are plant pathogens mostly parasitizing wild species of grasses as well as domesticated cereal crops. Genome analysis
of several smut fungi including Ustilago maydis revealed a singular clustered organization of genes encoding secreted effectors. In U. maydis, many of these clusters have a role in virulence. Reconstructing the evolutiona...
Author Summary
Because the speciation events that led to human, chimpanzee and gorilla were close in time, the genetic relationship of these species varies along the genome. While human and chimpanzee are the closest related species, in 15% of the genome, human and gorilla are more closely related, and in another 15% of the genome the chimpanzee an...
Background
Comparative analysis of homologous sequences enables the understanding of evolutionary patterns at the molecular level, unraveling the functional constraints that shaped the underlying genes. Bioinformatic pipelines for comparative sequence analysis typically include procedures for (i) alignment quality assessment and (ii) control of seq...
The human and chimpanzee X chromosomes are less divergent than expected based on autosomal divergence. This has led to a controversial hypothesis proposing a unique role of the X chromosome in human-chimpanzee speciation. We study incomplete lineage sorting patterns between humans, chimpanzees and gorillas to show that this low divergence is entire...
Significance
The X chromosome has a different inheritance pattern from the autosomes, direct interaction and potential conflict with the Y chromosome, and fewer copies than the autosomes. Natural selection may, therefore, act differently on the X chromosome. We analyze polymorphism patterns in 10 great ape species using 87 high-coverage whole genom...
Reconstructing the ancestral characteristics of species is a major goal in evolutionary and comparative biology. Unfortunately, fossils are not always available and sufficiently informative, and phylogenetic methods based on models of character evolution can be unsatisfactory. Genomic data offer a new opportunity to estimate ancestral character sta...
The unique inheritance pattern of X chromosomes makes them preferential
targets of adaptive evolution. We here investigate natural selection on the X
chromosome in all species of great apes. We find that diversity is more
strongly reduced around genes on the X compared with autosomes, and that a
higher proportion of substitutions results from posit...
Sequence alignments are the starting point for most evolutionary and comparative analyses. Full genome sequences can be compared to study patterns of within and between species variation. Genome sequence alignments are complex structures containing information such as coordinates, quality scores and synteny structure, which are stored in Multiple A...
Recombination is a major determinant of adaptive and non-adaptive evolution. Understanding how the recombination landscape has evolved in humans is thus key to the interpretation of human genomic evolution. Comparison of fine-scale recombination maps of human and chimpanzee has revealed large changes at fine genomic scales and conservation over lar...
Efficient algorithms and programs for the analysis of the ever-growing amount of biological sequence data are strongly needed
in the genomics era. The pace at which new data and methodologies are generated calls for the use of pre-existing, optimized—yet
extensible—code, typically distributed as libraries or packages. This motivated the Bio++ proje...
Source code for the CoalHMM.
(GZ)
Analysis results for all ape analyses.
(XLSX)
Report describing data analysis results not included in the main manuscript.
(PDF)
Report describing simulation experiments and results.
(PDF)
We present a hidden Markov model (HMM) for inferring gradual isolation between two populations during speciation, modelled as a time interval with restricted gene flow. The HMM describes the history of adjacent nucleotides in two genomic sequences, such that the nucleotides can be separated by recombination, can migrate between populations, or can...
In a genome alignment of five individuals of the ascomycete fungus Zymoseptoria pseudotritici, a close relative of the wheat pathogen Z. tritici (synonym Mycosphaerella graminicola), we observed peculiar diversity patterns. Long regions up to 100 kb without variation alternate with similarly long regions of high variability. The variable segments i...
