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Ute Krämer

    Ute Krämer

    Most well-characterized cases of adaptation involve single genetic loci. Theory suggests that multilocus adaptive walks should be common, but these are challenging to identify in natural populations. Here, we combine trait mapping with... more
    Most well-characterized cases of adaptation involve single genetic loci. Theory suggests that multilocus adaptive walks should be common, but these are challenging to identify in natural populations. Here, we combine trait mapping with population genetic modeling to show that a two-step process rewired nutrient homeostasis in a population of Arabidopsis as it colonized the base of an active stratovolcano characterized by extremely low soil manganese (Mn). First, a variant that disrupted the primary iron (Fe) uptake transporter gene ( IRT1 ) swept quickly to fixation in a hard selective sweep, increasing Mn but limiting Fe in the leaves. Second, multiple independent tandem duplications occurred at NRAMP1 and together rose to near fixation in the island population, compensating the loss of IRT1 by improving Fe homeostasis. This study provides a clear case of a multilocus adaptive walk and reveals how genetic variants reshaped a phenotype and spread over space and time.
    It is a plausible hypothesis that parallel adaptation events to the same environmental challenge should result in genetic changes of similar or identical effects, depending on the underlying fitness landscapes. However, systematic testing... more
    It is a plausible hypothesis that parallel adaptation events to the same environmental challenge should result in genetic changes of similar or identical effects, depending on the underlying fitness landscapes. However, systematic testing of this is scarce. Here we examine this hypothesis in two closely related plant species, <i>Arabidopsis halleri</i> and <i>Arabidopsis arenosa</i>, which co-occur at two calamine metalliferous sites harbouring toxic levels of the heavy metals zinc and cadmium. We conduct individual genome resequencing alongside soil elemental analysis for 64 plants from eight populations on metalliferous and non-metalliferous soils, and identify genomic footprints of selection and local adaptation. Selective sweep and environmental association analyses indicate a modest degree of gene as well as functional network convergence, whereby the proximal molecular factors mediating this convergence mostly differ between site pairs and species. Notably, we observe repeated selection on identical SNPs in several <i>A. halleri</i> genes at two independently colonized metalliferous sites. Our data suggest that species-specific metal handling and other biological features could explain a low degree of convergence between species. The parallel establishment of plant populations on calamine metalliferous soils involves convergent evolution, which will likely be more pervasive across sites purposely chosen for maximal similarity in soil composition.This article is part of the theme issue 'Convergent evolution in the genomics era: new insights and directions'.
    Peer reviewe
    ABSTRACTThe legume genus Lotus includes glycophytic forage crops and other species adapted to extreme environments, such as saline soils. Understanding salt tolerance mechanisms will contribute to the discovery of new traits which may... more
    ABSTRACTThe legume genus Lotus includes glycophytic forage crops and other species adapted to extreme environments, such as saline soils. Understanding salt tolerance mechanisms will contribute to the discovery of new traits which may enhance the breeding efforts towards improved performance of legumes in marginal agricultural environments. Here, we used a combination of ionomic and gas chromatography‐mass spectrometry (GC‐MS)‐based metabolite profilings of complete shoots (pooling leaves, petioles and stems) to compare the extremophile Lotus creticus, adapted to highly saline coastal regions, and two cultivated glycophytic grassland forage species, Lotus corniculatus and Lotus tenuis. L. creticus exhibited better survival after exposure to long‐term lethal salinity and was more efficient at excluding Cl‐ from the shoots than the glycophytes. In contrast, Na+ levels were higher in the extremophile under both control and salt stress, a trait often observed in halophytes. Ionomics dem...
    To maintain metal homeostasis within physiological limits independently of metal concentrations present in soil, plants developed a complex network including metal uptake, chelation, trafficking, and storage processes. In this network,... more
    To maintain metal homeostasis within physiological limits independently of metal concentrations present in soil, plants developed a complex network including metal uptake, chelation, trafficking, and storage processes. In this network, transporters have a central role. To study the molecular basis of zinc homeostasis in plants, we are using A. halleri, a zinc- and cadmium-tolerant and zinc-hyperaccumulating species representing the extreme end of natural variation in terms of metal homeostasis. Indeed, A. halleri stores high amount of metals in vacuoles of above-ground tissues (>1% Zn or 0.01% Cd in shoot dry weight). Cross-species transcriptomic studies identified about thirty genes which are constitutively over-expressed in A. halleri compared to its non-tolerant and non-hyperaccumulator sister species, Arabidopsis thaliana (1-3). HMA4 is one of these genes. It encodes a Zn/Cd plasmamembrane pump involved in xylem loading/unloading which is a key step in the hyperaccumulation process (4-5). The HMA4 overexpression is determined by a combination of gene triplication and cis-regulatory changes increasing transcription levels of each three HMA4 copies (5). We aim to identify the cis-elements underlying high expression of HMA4 in A. halleri using promoter-reporter constructs
    Diphthamide, a post-translationally modified histidine residue of eukaryotic TRANSLATION ELONGATION FACTOR2 (eEF2), is the human host cell-sensitizing target of diphtheria toxin. Diphthamide biosynthesis depends on the 4Fe-4S-cluster... more
    Diphthamide, a post-translationally modified histidine residue of eukaryotic TRANSLATION ELONGATION FACTOR2 (eEF2), is the human host cell-sensitizing target of diphtheria toxin. Diphthamide biosynthesis depends on the 4Fe-4S-cluster protein Dph1 catalyzing the first committed step, as well as Dph2 to Dph7, in yeast and mammals. Here we show that diphthamide modification of eEF2 is conserved inArabidopsis thalianaand requires AtDPH1. Ribosomal −1 frameshifting-error rates are increased in Arabidopsisdph1mutants, similar to yeast and mice. Compared to the wild type, shorter roots and smaller rosettes ofdph1mutants result from fewer formed cells. TARGET OF RAPAMYCIN (TOR) kinase activity is attenuated, and autophagy is activated, indph1mutants. Under abiotic stress diphthamide-unmodified eEF2 accumulates in wild-type seedlings, most strongly upon heavy metal excess, which is conserved in human cells. In summary, our results suggest that diphthamide contributes to the functionality of ...
    Book of Abstractinfo:eu-repo/semantics/publishe
    Mismatches with respect to ATH1 GeneChip probe sequences in representative reference datasets of A. halleri and A. lyrata. (XLSX 47 kb)
    Gene copy number expansions (CNEs) and reductions (CNRs) in A. halleri relative to A. thaliana generated for two datasets, each comprising one of the two A. halleri hybridizations and its in-silico replicate displaying the same amount of... more
    Gene copy number expansions (CNEs) and reductions (CNRs) in A. halleri relative to A. thaliana generated for two datasets, each comprising one of the two A. halleri hybridizations and its in-silico replicate displaying the same amount of within-sample variation as A. lyrata hybridizations. (PDF 23 kb)
    Numbers of genes predicted to exhibit copy number divergence in A. lyrata by comparison to A. thaliana. (XLSX 46 kb)
    It is a plausible hypothesis that parallel adaptation events to the same environmental challenge should result in genetic changes of similar or identical effects, depending on the underlying fitness landscapes. However, systematic testing... more
    It is a plausible hypothesis that parallel adaptation events to the same environmental challenge should result in genetic changes of similar or identical effects, depending on the underlying fitness landscapes. However, systematic testing of this is scarce. Here we examine this hypothesis in two closely related plant species, <i>Arabidopsis halleri</i> and <i>Arabidopsis arenosa</i>, which co-occur at two calamine metalliferous sites harbouring toxic levels of the heavy metals zinc and cadmium. We conduct individual genome resequencing alongside soil elemental analysis for 64 plants from eight populations on metalliferous and non-metalliferous soils, and identify genomic footprints of selection and local adaptation. Selective sweep and environmental association analyses indicate a modest degree of gene as well as functional network convergence, whereby the proximal molecular factors mediating this convergence mostly differ between site pairs and species. Nota...
    This paper is available online free of all access charges (see
    Heterogeneous distribution of Zn stable isotopes in mice FREDERIC MOYNIER1, TOSHIYUKII FUJII2, ANDREY S SHAW3 AND MARIE LE BORGNE3 1Department of Earth and Planetary Science and McDonnell Center for Space Sciences, Washington University... more
    Heterogeneous distribution of Zn stable isotopes in mice FREDERIC MOYNIER1, TOSHIYUKII FUJII2, ANDREY S SHAW3 AND MARIE LE BORGNE3 1Department of Earth and Planetary Science and McDonnell Center for Space Sciences, Washington University in St Louis. moynier@levee.wustl.edu 2Research Reactor Institute, Kyoto University, 2-1010 Asashiro Nishi, Kumatori, Sennan, Osaka 590-0494, Japan. tosiyuki@rri.kyoto-u.ac.jp 3 Department of Pathology and Immunology and Howard Hughes Medical Institute, Washington University School of Medicine in St Louis. shaw@pathology.wustl.edu; mleborgne@pathology.wustl.edu
    Significance Multidrug-resistant bacteria present an acute problem to medicine, generating interest in novel antimicrobial strategies. Antimicrobial peptides currently are being investigated, both as antibiotics and as immunomodulatory... more
    Significance Multidrug-resistant bacteria present an acute problem to medicine, generating interest in novel antimicrobial strategies. Antimicrobial peptides currently are being investigated, both as antibiotics and as immunomodulatory agents. Many antimicrobial peptides interact with the bacterial membrane, a previously underexplored antibiotic target. We present a system-based study of the mode of action of small cationic peptides and the mechanisms that bacteria use to defend against them. We show that peptide integration into the membrane causes delocalization of essential peripheral membrane proteins. This delocalization impacts on two cellular processes, namely respiration and cell-wall biosynthesis. We describe a bacterial survival strategy in which mechanosensitive channels in the bacterial membrane establish osmoprotection against membrane-targeting bacteriolytic peptides. Understanding the peptides' mode of action and bacterial survival strategies opens up new avenues ...
    IRON-REGULATED TRANSPORTER1 (IRT1) is the root high-affinity ferrous iron uptake system and indispensable for the completion of the life cycle of Arabidopsis thaliana without vigorous iron (Fe) supplementation. Here we provide evidence... more
    IRON-REGULATED TRANSPORTER1 (IRT1) is the root high-affinity ferrous iron uptake system and indispensable for the completion of the life cycle of Arabidopsis thaliana without vigorous iron (Fe) supplementation. Here we provide evidence supporting a second role of IRT1 in root-to-shoot partitioning of Fe. We show that irt1 mutants over-accumulate Fe in roots, most prominently in the cortex of the differentiation zone in irt1-2, compared to the wild type. Shoots of irt1-2 are severely Fe-deficient according to Fe content and marker transcripts, as expected. We generated irt1-2 lines producing IRT1 mutant variants carrying single amino-acid substitutions of key residues in transmembrane helices IV and V, Ser206 and His232 , which are required for transport activity in yeast. Root short-term 55 Fe uptake rates were uninformative concerning IRT1-mediated transport. Overall irt1-like concentrations of the secondary substrate Mn suggested that the transgenic Arabidopsis lines also remain incapable of IRT1-mediated root Fe uptake. Yet, IRT1S206A partially complements rosette dwarfing and leaf chlorosis, as well as root-to-shoot Fe partitioning and gene expression defects of irt1-2, all of which are fully complemented by wild-type IRT1. Taken together, these results suggest a function for IRT1 in root-to-shoot Fe partitioning that does not require Fe transport activity of IRT1. Among the genes of which transcript levels are partially dependent on IRT1, we identify MYB DOMAIN PROTEIN10, MYB DOMAIN PROTEIN72 and NICOTIANAMINE SYNTHASE4 as candidates for effecting IRT1-dependent Fe mobilization in roots. Understanding the biological functions of IRT1 will help to improve iron nutrition and the nutritional quality of agricultural crops.
    Complete dataset expanded from Additional file 3. (XLS 16282 kb)
    Validation of array-CGH results against all genes predicted to be (A) copy number expanded (CNEs) and (B) copy number reduced (CNRs) in A. lyrata (see Table 1). (XLSX 43 kb)
    Representative reference datasets. Summary of number and position of sequence-probe hybridization mismatches relative to A. thaliana gene sequence. (XLSX 73 kb)
    Gold standard dataset of genes of known copy number in A. halleri. (XLSX 40 kb)
    Manually curated list of MapMan transition metal homeostasis genes of A. thaliana. (XLSX 44 kb)
    List of copy number expanded and copy number reduced genes in A. halleri and A. lyrata, by comparison to A. thaliana. (XLSX 1331 kb)
    It is a plausible hypothesis that parallel adaptation events to the same environmental challenge should result in genetic changes of similar or identical effects, depending on the underlying fitness landscapes. However, systematic testing... more
    It is a plausible hypothesis that parallel adaptation events to the same environmental challenge should result in genetic changes of similar or identical effects, depending on the underlying fitness landscapes. However, systematic testing of this is scarce. Here we examine this hypothesis in two closely related plant species, <i>Arabidopsis halleri</i> and <i>Arabidopsis arenosa</i>, which co-occur at two calamine metalliferous sites harbouring toxic levels of the heavy metals zinc and cadmium. We conduct individual genome resequencing alongside soil elemental analysis for 64 plants from eight populations on metalliferous and non-metalliferous soils, and identify genomic footprints of selection and local adaptation. Selective sweep and environmental association analyses indicate a modest degree of gene as well as functional network convergence, whereby the proximal molecular factors mediating this convergence mostly differ between site pairs and species. Nota...
    It is a plausible hypothesis that parallel adaptation events to the same environmental challenge should result in genetic changes of similar or identical effects, depending on the underlying fitness landscapes. However, systematic testing... more
    It is a plausible hypothesis that parallel adaptation events to the same environmental challenge should result in genetic changes of similar or identical effects, depending on the underlying fitness landscapes. However, systematic testing of this is scarce. Here we examine this hypothesis in two closely related plant species, <i>Arabidopsis halleri</i> and <i>Arabidopsis arenosa</i>, which co-occur at two calamine metalliferous sites harbouring toxic levels of the heavy metals zinc and cadmium. We conduct individual genome resequencing alongside soil elemental analysis for 64 plants from eight populations on metalliferous and non-metalliferous soils, and identify genomic footprints of selection and local adaptation. Selective sweep and environmental association analyses indicate a modest degree of gene as well as functional network convergence, whereby the proximal molecular factors mediating this convergence mostly differ between site pairs and species. Nota...
    It is a plausible hypothesis that parallel adaptation events to the same environmental challenge should result in genetic changes of similar or identical effects, depending on the underlying fitness landscapes. However, systematic testing... more
    It is a plausible hypothesis that parallel adaptation events to the same environmental challenge should result in genetic changes of similar or identical effects, depending on the underlying fitness landscapes. However, systematic testing of this is scarce. Here we examine this hypothesis in two closely related plant species, <i>Arabidopsis halleri</i> and <i>Arabidopsis arenosa</i>, which co-occur at two calamine metalliferous sites harbouring toxic levels of the heavy metals zinc and cadmium. We conduct individual genome resequencing alongside soil elemental analysis for 64 plants from eight populations on metalliferous and non-metalliferous soils, and identify genomic footprints of selection and local adaptation. Selective sweep and environmental association analyses indicate a modest degree of gene as well as functional network convergence, whereby the proximal molecular factors mediating this convergence mostly differ between site pairs and species. Nota...
    It is a plausible hypothesis that parallel adaptation events to the same environmental challenge should result in genetic changes of similar or identical effects, depending on the underlying fitness landscapes. However, systematic testing... more
    It is a plausible hypothesis that parallel adaptation events to the same environmental challenge should result in genetic changes of similar or identical effects, depending on the underlying fitness landscapes. However, systematic testing of this is scarce. Here we examine this hypothesis in two closely related plant species, <i>Arabidopsis halleri</i> and <i>Arabidopsis arenosa</i>, which co-occur at two calamine metalliferous sites harbouring toxic levels of the heavy metals zinc and cadmium. We conduct individual genome resequencing alongside soil elemental analysis for 64 plants from eight populations on metalliferous and non-metalliferous soils, and identify genomic footprints of selection and local adaptation. Selective sweep and environmental association analyses indicate a modest degree of gene as well as functional network convergence, whereby the proximal molecular factors mediating this convergence mostly differ between site pairs and species. Nota...

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