Fitness Landscape Transformation through a Single Amino Acid Change in the Rho Terminator
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{"title"=>"Fitness landscape transformation through a single Amino acid change in the rho terminator", "type"=>"journal", "authors"=>[{"first_name"=>"Peter L.", "last_name"=>"Freddolino", "scopus_author_id"=>"8631632200"}, {"first_name"=>"Hani", "last_name"=>"Goodarzi", "scopus_author_id"=>"8512690300"}, {"first_name"=>"Saeed", "last_name"=>"Tavazoie", "scopus_author_id"=>"6602990026"}], "year"=>2012, "source"=>"PLoS Genetics", "identifiers"=>{"pui"=>"365220753", "sgr"=>"84863654995", "issn"=>"15537390", "pmid"=>"22693458", "scopus"=>"2-s2.0-84863654995", "doi"=>"10.1371/journal.pgen.1002744", "isbn"=>"1553-7404 (Electronic)\\r1553-7390 (Linking)"}, "id"=>"2837579d-4833-320d-84a7-54b4298c85db", "abstract"=>"Regulatory networks allow organisms to match adaptive behavior to the complex and dynamic contingencies of their native habitats. Upon a sudden transition to a novel environment, the mismatch between the native behavior and the new niche provides selective pressure for adaptive evolution through mutations in elements that control gene expression. In the case of core components of cellular regulation and metabolism, with broad control over diverse biological processes, such mutations may have substantial pleiotropic consequences. Through extensive phenotypic analyses, we have characterized the systems-level consequences of one such mutation (rho*) in the global transcriptional terminator Rho of Escherichia coli. We find that a single amino acid change in Rho results in a massive change in the fitness landscape of the cell, with widely discrepant fitness consequences of identical single locus perturbations in rho* versus rho(WT) backgrounds. Our observations reveal the extent to which a single regulatory mutation can transform the entire fitness landscape of the cell, causing a massive change in the interpretation of individual mutations and altering the evolutionary trajectories which may be accessible to a bacterial population.", "link"=>"http://www.mendeley.com/research/fitness-landscape-transformation-through-single-amino-acid-change-rho-terminator", "reader_count"=>53, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>4, "Student > Doctoral Student"=>2, "Researcher"=>15, "Student > Ph. D. Student"=>14, "Student > Postgraduate"=>1, "Student > Master"=>8, "Other"=>1, "Student > Bachelor"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>5}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>4, "Student > Doctoral Student"=>2, "Researcher"=>15, "Student > Ph. D. Student"=>14, "Student > Postgraduate"=>1, "Student > Master"=>8, "Other"=>1, "Student > Bachelor"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>5}, "reader_count_by_subject_area"=>{"Engineering"=>3, "Unspecified"=>2, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>8, "Agricultural and Biological Sciences"=>38, "Medicine and Dentistry"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>3}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>38}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>8}, "Unspecified"=>{"Unspecified"=>2}, "Environmental Science"=>{"Environmental Science"=>1}}, "reader_count_by_country"=>{"Iran"=>1, "United States"=>1, "France"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/629395"], "description"=>"<p>(A) Key pathways showing significant patterns of over- or under-expression in <i>rho</i>* cells, assessed using iPAGE <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002744#pgen.1002744-Goodarzi3\" target=\"_blank\">[16]</a>. The log ratios of <i>rho</i>* to WT RNA at each probe were discretized as shown at the head of each chart (breaks correspond to 3, 2, and 1.5-fold differences in either direction). For each pathway, coloring at each cluster corresponds to the degree of over- or under-representation of that cluster in the relative expression level of genes in that pathway (with magnitude equal to the negative log<sub>10</sub> p-value for significance of the representation; positive and negative scores represent over- and under-representation, respectively). (B) Ratios of <i>rho</i>* to WT growth rates under a variety of conditions showing significant fitness differences; dashed lines indicate the ratio under the reference condition (black) or for equal growth rates (green). Error bars show a 95% confidence interval based on 10,000 samples from the posterior parameter distribution (see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002744#pgen.1002744.s021\" target=\"_blank\">Text S1</a>, Section 1.3). Abbreviations are shown in <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002744#pgen.1002744.s019\" target=\"_blank\">Table S10</a>. See <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002744#pgen-1002744-t001\" target=\"_blank\">Table 1</a> for concentrations of antibiotics used. Ratios of <i>rho*</i> to WT growth rates differ significantly from that in the reference condition M9t/glucose (non-overlapping 95% confidence intervals) for all cases except LB, which is included simply as a second useful reference.</p>", "links"=>[], "tags"=>["transcriptional", "phenotypic", "differences", "wt"], "article_id"=>299885, "categories"=>["Genetics", "Microbiology", "Evolutionary Biology"], "users"=>["Peter L. Freddolino", "Hani Goodarzi", "Saeed Tavazoie"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002744.g001", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_transcriptional_and_phenotypic_differences_between_WT_and_rho_cells_/299885", "title"=>"Comparison of transcriptional and phenotypic differences between WT and <i>rho</i>* cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-05-31 02:44:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/629578"], "description"=>"<p>Bar charts show, from left, the number of genes, intergenic regions, and pathways identified as having informative over- or under-representations of transposon insertions (see main text and <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002744#pgen.1002744.s021\" target=\"_blank\">Text S1</a>, Section 1.5 for details). Categories which appeared as significant in both WT and <i>rho</i>* data are further subdivided based on whether the pattern of enrichment and depletion was correlated in the two backgrounds.</p>", "links"=>[], "tags"=>["backgrounds", "remarkably"], "article_id"=>300073, "categories"=>["Genetics", "Microbiology", "Evolutionary Biology"], "users"=>["Peter L. Freddolino", "Hani Goodarzi", "Saeed Tavazoie"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002744.g003", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_WT_and_rho_backgrounds_show_remarkably_different_fitness_landscapes_/300073", "title"=>"WT and <i>rho</i>* backgrounds show remarkably different fitness landscapes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-05-31 00:01:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/629837"], "description"=>"<p>Growth rates of selected strain/condition combinations are defined as described in the <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002744#s4\" target=\"_blank\">Methods</a> section of the main text. All growth rates are in doublings/hour and include 95% confidence intervals from sampling of the posterior model parameter distributions (see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002744#pgen.1002744.s021\" target=\"_blank\">Text S1</a>, Section 1.3). Significance of differences was assessed relative to growth in M9t/glucose as described in the caption for <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002744#pgen-1002744-g001\" target=\"_blank\">Figure 1</a>. Growth in LB did not differ significantly from growth in M9t/glucose, but is included as a useful reference point. Numbers of technical replicates used for each growth rate are given in <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002744#pgen.1002744.s020\" target=\"_blank\">Table S11</a>. Abbreviations are listed in <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002744#pgen.1002744.s019\" target=\"_blank\">Table S10</a>.</p>†<p>: Effective growth rate; see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002744#pgen.1002744.s021\" target=\"_blank\">Text S1</a> for details. Concentrations of additives are given in µg/mL unless otherwise noted.</p>", "links"=>[], "tags"=>["differences", "wt", "cells"], "article_id"=>300327, "categories"=>["Genetics", "Microbiology", "Evolutionary Biology"], "users"=>["Peter L. Freddolino", "Hani Goodarzi", "Saeed Tavazoie"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002744.t001", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Conditions_showing_significant_differences_in_growth_rate_between_WT_and_rho_cells_relative_to_growth_in_M9t_glucose_/300327", "title"=>"Conditions showing significant differences in growth rate between WT and <i>rho</i>* cells (relative to growth in M9t/glucose).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-05-31 00:05:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/629702"], "description"=>"<p>Ratios of growth rates for each strain to those for the <i>rho</i>*/<i>rpsL</i>* double mutant are shown for all permutations of mutant and wild type alleles at these loci, in LB (left) or LB plus 5.5% ethanol (right). See Section 5 of <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002744#pgen.1002744.s021\" target=\"_blank\">Text S1</a> for details on growth rate determination in ethanol-containing media. Error bars indicate 95% confidence intervals. Predictions for the double mutant in the absence of epistasis are made using a multiplicative model (see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002744#pgen.1002744.s021\" target=\"_blank\">Text S1</a>, Section 4). Such predictions are not possible in LB+EtOH due to the lack of <i>rho</i><sup>WT</sup> and <i>rpsL</i>* growth.</p>", "links"=>[], "tags"=>["epistatic", "interactions", "ethanol"], "article_id"=>300200, "categories"=>["Genetics", "Microbiology", "Evolutionary Biology"], "users"=>["Peter L. Freddolino", "Hani Goodarzi", "Saeed Tavazoie"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002744.g005", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Contributions_of_rho_rpsL_epistatic_interactions_to_ethanol_tolerance_/300200", "title"=>"Contributions of <i>rho</i>*-<i>rpsL</i>* epistatic interactions to ethanol tolerance.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-05-31 00:03:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/327236", "https://ndownloader.figshare.com/files/327308", "https://ndownloader.figshare.com/files/327370", "https://ndownloader.figshare.com/files/327424", "https://ndownloader.figshare.com/files/327459", "https://ndownloader.figshare.com/files/327497", "https://ndownloader.figshare.com/files/327549", "https://ndownloader.figshare.com/files/327604", "https://ndownloader.figshare.com/files/327654", "https://ndownloader.figshare.com/files/327718", "https://ndownloader.figshare.com/files/327770", "https://ndownloader.figshare.com/files/327827", "https://ndownloader.figshare.com/files/327875", "https://ndownloader.figshare.com/files/327917", "https://ndownloader.figshare.com/files/327970", "https://ndownloader.figshare.com/files/328021", "https://ndownloader.figshare.com/files/328084", "https://ndownloader.figshare.com/files/328146", "https://ndownloader.figshare.com/files/328182", "https://ndownloader.figshare.com/files/328224", "https://ndownloader.figshare.com/files/328284"], "description"=>"<div><p>Regulatory networks allow organisms to match adaptive behavior to the complex and dynamic contingencies of their native habitats. Upon a sudden transition to a novel environment, the mismatch between the native behavior and the new niche provides selective pressure for adaptive evolution through mutations in elements that control gene expression. In the case of core components of cellular regulation and metabolism, with broad control over diverse biological processes, such mutations may have substantial pleiotropic consequences. Through extensive phenotypic analyses, we have characterized the systems-level consequences of one such mutation (<em>rho</em>*) in the global transcriptional terminator Rho of <em>Escherichia coli</em>. We find that a single amino acid change in Rho results in a massive change in the fitness landscape of the cell, with widely discrepant fitness consequences of identical single locus perturbations in <em>rho</em>* versus <em>rho</em><sup>WT</sup> backgrounds. Our observations reveal the extent to which a single regulatory mutation can transform the entire fitness landscape of the cell, causing a massive change in the interpretation of individual mutations and altering the evolutionary trajectories which may be accessible to a bacterial population.</p> </div>", "links"=>[], "tags"=>["amino", "rho", "terminator"], "article_id"=>124593, "categories"=>["Genetics", "Microbiology", "Evolutionary Biology"], "users"=>["Peter L. Freddolino", "Hani Goodarzi", "Saeed Tavazoie"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1002744.s001", "https://dx.doi.org/10.1371/journal.pgen.1002744.s002", "https://dx.doi.org/10.1371/journal.pgen.1002744.s003", "https://dx.doi.org/10.1371/journal.pgen.1002744.s004", "https://dx.doi.org/10.1371/journal.pgen.1002744.s005", "https://dx.doi.org/10.1371/journal.pgen.1002744.s006", "https://dx.doi.org/10.1371/journal.pgen.1002744.s007", "https://dx.doi.org/10.1371/journal.pgen.1002744.s008", "https://dx.doi.org/10.1371/journal.pgen.1002744.s009", "https://dx.doi.org/10.1371/journal.pgen.1002744.s010", "https://dx.doi.org/10.1371/journal.pgen.1002744.s011", "https://dx.doi.org/10.1371/journal.pgen.1002744.s012", "https://dx.doi.org/10.1371/journal.pgen.1002744.s013", "https://dx.doi.org/10.1371/journal.pgen.1002744.s014", "https://dx.doi.org/10.1371/journal.pgen.1002744.s015", "https://dx.doi.org/10.1371/journal.pgen.1002744.s016", "https://dx.doi.org/10.1371/journal.pgen.1002744.s017", "https://dx.doi.org/10.1371/journal.pgen.1002744.s018", "https://dx.doi.org/10.1371/journal.pgen.1002744.s019", "https://dx.doi.org/10.1371/journal.pgen.1002744.s020", "https://dx.doi.org/10.1371/journal.pgen.1002744.s021"], "stats"=>{"downloads"=>30, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Fitness_Landscape_Transformation_through_a_Single_Amino_Acid_Change_in_the_Rho_Terminator/124593", "title"=>"Fitness Landscape Transformation through a Single Amino Acid Change in the Rho Terminator", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-05-31 01:16:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/629778"], "description"=>"<p>Shown is a cartoon of the relative fitness of <i>rho</i>* vs. <i>rho</i><sup>WT</sup> cells under typical growth conditions (blue) or a stress condition (red), with genotypic variations running along the x axis. Genotype A in each case represents a wild type background (aside from the status at <i>rho</i>). <i>rho</i>* may directly alter fitness under the stress conditions, interact epistatically with secondary mutations (genotype B, <i>e.g.</i> Δ<i>visC</i>), and uncover further beneficial mutations under stress conditions (genotype C, <i>e.g. rpsL*</i>).</p>", "links"=>[], "tags"=>["caused"], "article_id"=>300272, "categories"=>["Genetics", "Microbiology", "Evolutionary Biology"], "users"=>["Peter L. Freddolino", "Hani Goodarzi", "Saeed Tavazoie"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002744.g006", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Transformation_of_the_fitness_landscape_caused_by_rho_/300272", "title"=>"Transformation of the fitness landscape caused by <i>rho</i>*.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-05-31 00:04:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/629641"], "description"=>"<p>For each combination of a secondary mutation <i>A</i> and media condition (shown on the <i><sub>x</sub></i> axis) considered in our follow-up experiments, the multiplicative epistasis ε<i><sub>rho*,A</sub></i> (see Eq. S7) is plotted, along with error bars showing a 95% confidence interval (see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002744#pgen.1002744.s021\" target=\"_blank\">Text S1</a>, Section 1.3). Significant interactions (those for which the confidence intervals do not overlap with zero) are colored according to their sign. Positive values of ε<i><sub>rho*,A</sub></i> indicate positive epistasis between <i>rho</i>* and the secondary mutation in question (<i>i.e.</i>, the fitness of the double mutant is higher than that expected based on the effects of the two mutations in isolation). Complete data for all strains are given in <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002744#pgen.1002744.s013\" target=\"_blank\">Table S4</a>. <i>rpsL</i>* strains in LB+ethanol are not shown due to the complete absence of wild type growth in this condition.</p>", "links"=>[], "tags"=>["interactions"], "article_id"=>300142, "categories"=>["Genetics", "Microbiology", "Evolutionary Biology"], "users"=>["Peter L. Freddolino", "Hani Goodarzi", "Saeed Tavazoie"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002744.g004", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Epistatic_interactions_between_rho_and_secondary_mutations_/300142", "title"=>"Epistatic interactions between <i>rho</i>* and secondary mutations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-05-31 00:02:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/629481"], "description"=>"<p>(A) Procedure used to identify loci with significant fitness contributions. Transposon mutagenized libraries were constructed separately in the WT and <i>rho</i>* strains, and then grown in parallel under selective conditions and a reference condition. Genomic regions adjacent to transposons were then selectively amplified. The abundances of transposon insertions throughout the genome were compared between the condition of interest and the reference condition using a two-color microarray. (B) Selective conditions used; M9t/glucose was the reference condition in all cases. (C) Comparison of gene-wise median fitness scores (log<sub>2</sub> ratio of reference∶selected microarray signals) between WT and <i>rho</i>* cells under each condition. For reference, a similar comparison between the two biological replicates of each strain/condition pairing is also shown. Pearson correlations (r) are given between WT and <i>rho</i>* signals or between replicate experiments for isogenic cells, as appropriate.</p>", "links"=>[], "tags"=>["landscapes", "wt", "cells", "transposon-mutagenized"], "article_id"=>299977, "categories"=>["Genetics", "Microbiology", "Evolutionary Biology"], "users"=>["Peter L. Freddolino", "Hani Goodarzi", "Saeed Tavazoie"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002744.g002", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mapping_of_fitness_landscapes_of_WT_and_rho_cells_using_transposon_mutagenized_libraries_/299977", "title"=>"Mapping of fitness landscapes of WT and <i>rho</i>* cells using transposon-mutagenized libraries.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-05-31 02:46:17"}

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Relative Metric

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