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• {"link"=>{"url"=>"http://www.citeulike.org/user/jjray/article/12473725"}, "post_time"=>"2013-07-10 21:39:35", "tag"=>["epistasis", "evolution", "fitness_landscape", "genetics"], "linkout"=>{"type"=>"DOI", "url"=>"http://dx.doi.org/10.1371/journal.pgen.1003580"}, "username"=>"jjray", "article_id"=>"12473725"}
• {"link"=>{"url"=>"http://www.citeulike.org/user/vincentoostelbos/article/12473725"}, "post_time"=>"2014-01-15 19:31:02", "tag"=>["biology", "computational_biology", "epistasis", "evolution", "fitness_landscape", "genetics"], "linkout"=>{"type"=>"DOI", "url"=>"http://dx.doi.org/10.1371/journal.pgen.1003580"}, "username"=>"vincentoostelbos", "article_id"=>"12473725"}

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{"title"=>"Environmental Dependence of Genetic Constraint", "type"=>"journal", "authors"=>[{"first_name"=>"Marjon G J", "last_name"=>"de Vos", "scopus_author_id"=>"35095022400"}, {"first_name"=>"Frank J.", "last_name"=>"Poelwijk", "scopus_author_id"=>"14007979400"}, {"first_name"=>"Nico", "last_name"=>"Battich", "scopus_author_id"=>"55780842800"}, {"first_name"=>"Joseph D T", "last_name"=>"Ndika", "scopus_author_id"=>"55037265900"}, {"first_name"=>"Sander J.", "last_name"=>"Tans", "scopus_author_id"=>"6602741809"}], "year"=>2013, "source"=>"PLoS Genetics", "identifiers"=>{"isbn"=>"10.1371/journal.pgen.1003580", "pmid"=>"23825963", "doi"=>"10.1371/journal.pgen.1003580", "pui"=>"369235342", "issn"=>"15537390", "sgr"=>"84879630282", "scopus"=>"2-s2.0-84879630282"}, "id"=>"5a704394-a3d6-3008-9ecc-8274c79c60b6", "abstract"=>"The epistatic interactions that underlie evolutionary constraint have mainly been studied for constant external conditions. However, environmental changes may modulate epistasis and hence affect genetic constraints. Here we investigate genetic constraints in the adaptive evolution of a novel regulatory function in variable environments, using the lac repressor, LacI, as a model system. We have systematically reconstructed mutational trajectories from wild type LacI to three different variants that each exhibit an inverse response to the inducing ligand IPTG, and analyzed the higher-order interactions between genetic and environmental changes. We find epistasis to depend strongly on the environment. As a result, mutational steps essential to inversion but inaccessible by positive selection in one environment, become accessible in another. We present a graphical method to analyze the observed complex higher-order interactions between multiple mutations and environmental change, and show how the interactions can be explained by a combination of mutational effects on allostery and thermodynamic stability. This dependency of genetic constraint on the environment should fundamentally affect evolutionary dynamics and affects the interpretation of phylogenetic data.", "link"=>"http://www.mendeley.com/research/environmental-dependence-genetic-constraint", "reader_count"=>62, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>3, "Researcher"=>21, "Student > Ph. D. Student"=>20, "Student > Postgraduate"=>5, "Student > Master"=>8, "Other"=>2, "Student > Bachelor"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>3, "Researcher"=>21, "Student > Ph. D. Student"=>20, "Student > Postgraduate"=>5, "Student > Master"=>8, "Other"=>2, "Student > Bachelor"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>12, "Agricultural and Biological Sciences"=>37, "Medicine and Dentistry"=>2, "Physics and Astronomy"=>6, "Chemical Engineering"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Physics and Astronomy"=>{"Physics and Astronomy"=>6}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>37}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>12}, "Unspecified"=>{"Unspecified"=>3}, "Environmental Science"=>{"Environmental Science"=>1}, "Chemical Engineering"=>{"Chemical Engineering"=>1}}, "reader_count_by_country"=>{"Canada"=>1, "Austria"=>1, "United States"=>1, "France"=>2, "Switzerland"=>1}, "group_count"=>0}

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• http://doi.org/10.1073/pnas.1510282112
• http://doi.org/10.1093/molbev/msx185
• http://doi.org/10.1209/0295-5075/122/58002
• http://doi.org/10.1016/j.tpb.2017.10.006
• http://doi.org/10.1039/C4MB00181H
• http://doi.org/10.1371/journal.pone.0084398
• http://doi.org/10.3390/biology5020024
• http://doi.org/10.1016/j.gde.2015.08.008
• http://doi.org/10.1534/genetics.117.300519
• http://doi.org/10.1093/molbev/msz211
• http://doi.org/10.1093/molbev/msv269
• http://doi.org/10.3390/metabo5020311
• http://doi.org/10.15252/msb.20156444
• http://doi.org/10.1111/evo.13175
• http://doi.org/10.1016/j.bpj.2016.05.030
• http://doi.org/10.1016/j.tig.2018.06.004
• http://doi.org/10.1111/eva.12846
• http://doi.org/10.1113/jphysiol.2014.272625
• http://doi.org/10.7554/eLife.25192
• http://doi.org/10.15252/msb.20178102
• http://doi.org/10.1111/nph.14646
• http://doi.org/10.1371/journal.pgen.1008801
• http://doi.org/10.1086/684104
• http://doi.org/10.1016/j.tig.2014.04.003
• http://doi.org/10.1128/mBio.02232-19
• http://doi.org/10.1099/mic.0.000126
• http://doi.org/10.1146/annurev-biophys-070317-032939
• http://doi.org/10.1038/s41559-018-0549-8
• http://doi.org/10.1038/nrg3744
• http://doi.org/10.1534/genetics.115.180299

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• {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fplosgenetics%2Farticle%3Fid%3D10.1371%252Fjournal.pgen.1003580", "share_count"=>0, "like_count"=>0, "comment_count"=>0, "click_count"=>0, "total_count"=>0}

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• {"id"=>"350759198310666240", "text"=>"GxGxE all the cool kids study third order interactions!\n#PLOSGenetics: Environmental Dependence of Genetic Constraint http://t.co/WiW6AlrFc1", "created_at"=>"2013-06-28T23:34:44Z", "user"=>"IanDworkin", "user_name"=>"Ian Dworkin", "user_profile_image"=>"http://a0.twimg.com/profile_images/3154151095/3788d5de7a75dafb33d17c6108456cbc_normal.jpeg"}
• {"id"=>"350870857561808898", "text"=>"MT @IanDworkin GxGxE - 3rd order interactions @PLOSGenetics: Environmental Dependence of Genetic Constraint http://t.co/1wgJYC7GLA", "created_at"=>"2013-06-29T06:58:25Z", "user"=>"TrendsGenetics", "user_name"=>"Trends in Genetics", "user_profile_image"=>"http://a0.twimg.com/profile_images/2750580405/d136341b3bb07c6bede69e92eca5a2e7_normal.jpeg"}
• {"id"=>"350976178414297090", "text"=>"Epistasis depends strongly on the environment, cool article: http://t.co/IbC8nyMN0h via @PLOSGenetics", "created_at"=>"2013-06-29T13:56:56Z", "user"=>"jcoolon", "user_name"=>"Joseph Coolon", "user_profile_image"=>"http://a0.twimg.com/profile_images/378800000021416267/4773310d19a9e831eaf90d9f25c6c231_normal.jpeg"}

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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/1103766", "https://ndownloader.figshare.com/files/1103767", "https://ndownloader.figshare.com/files/1103768", "https://ndownloader.figshare.com/files/1103769", "https://ndownloader.figshare.com/files/1103770"], "description"=>"<div><p>The epistatic interactions that underlie evolutionary constraint have mainly been studied for constant external conditions. However, environmental changes may modulate epistasis and hence affect genetic constraints. Here we investigate genetic constraints in the adaptive evolution of a novel regulatory function in variable environments, using the <i>lac</i> repressor, LacI, as a model system. We have systematically reconstructed mutational trajectories from wild type LacI to three different variants that each exhibit an inverse response to the inducing ligand IPTG, and analyzed the higher-order interactions between genetic and environmental changes. We find epistasis to depend strongly on the environment. As a result, mutational steps essential to inversion but inaccessible by positive selection in one environment, become accessible in another. We present a graphical method to analyze the observed complex higher-order interactions between multiple mutations and environmental change, and show how the interactions can be explained by a combination of mutational effects on allostery and thermodynamic stability. This dependency of genetic constraint on the environment should fundamentally affect evolutionary dynamics and affects the interpretation of phylogenetic data.</p></div>", "links"=>[], "tags"=>["Biochemistry", "biophysics", "Computational biology", "ecology", "Evolutionary biology", "genetics", "microbiology", "systems biology", "dependence"], "article_id"=>733613, "categories"=>["Physics", "Biological Sciences"], "users"=>["Marjon G. J. de Vos", "Frank J. Poelwijk", "Nico Battich", "Joseph D. T. Ndika", "Sander J. Tans"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003580.s001", "https://dx.doi.org/10.1371/journal.pgen.1003580.s002", "https://dx.doi.org/10.1371/journal.pgen.1003580.s003", "https://dx.doi.org/10.1371/journal.pgen.1003580.s004", "https://dx.doi.org/10.1371/journal.pgen.1003580.s005"], "stats"=>{"downloads"=>1, "page_views"=>33, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Environmental_Dependence_of_Genetic_Constraint_/733613", "title"=>"Environmental Dependence of Genetic Constraint", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-06-27 03:13:50"}
• {"files"=>["https://ndownloader.figshare.com/files/1103762"], "description"=>"<p>The three inverse LacI variants all contain three mutations. Each mutation is represented by a vector (see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003580#pgen-1003580-g002\" target=\"_blank\">Figure 2</a>). The axes indicate expression without IPTG in Env₀ and expression with IPTG in Env₁. Expression levels in both environments are normalized to the LacI_wt level. Note that expression along the vertical axis is represented as (Expression)⁻¹, as during inversion the expression level in Env₁ decreases. The inverse, triple mutant, is located in the upper right corner of the plot. A) LacI_inv1: S97P (blue), R207L (green), T258A (red). B) LacI_inv2: S97P (blue), L307H (green), L349P (red). C) LacI_inv3: S97P (blue), G315D (green), P339H (red). The significance of the phenotypic effect of mutations is tested with a <i>t</i>-test with Bonferroni correction for multiple comparisons (<i>P</i><0.05), error-bars are standard deviations, n = 3.</p>", "links"=>[], "tags"=>["Biochemistry", "biophysics", "Computational biology", "ecology", "Evolutionary biology", "genetics", "microbiology", "systems biology", "trajectories", "inverse", "laci"], "article_id"=>733609, "categories"=>["Physics", "Biological Sciences"], "users"=>["Marjon G. J. de Vos", "Frank J. Poelwijk", "Nico Battich", "Joseph D. T. Ndika", "Sander J. Tans"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003580.g003", "stats"=>{"downloads"=>1, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Adaptive_trajectories_towards_the_three_inverse_LacI_variants_/733609", "title"=>"Adaptive trajectories towards the three inverse LacI variants.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-27 03:13:50"}
• {"files"=>["https://ndownloader.figshare.com/files/1103760"], "description"=>"<p>A) Schematic representation of the genetic system in <i>E. coli</i>. The <i>lac</i> repressor, LacI, controls expression of LacZ. The system responds to IPTG. IPTG acts as an inducer in the wild type LacI (blue block-arrow), and as a co-repressor in the phenotypically inverse mutants (red arrow). B) Environmental dependence of the expression level of lacZ. Expression levels are measured in two environments. For the wild type LacI (LacI_wt), LacZ expression level is high in the presence of IPTG (Env₁) and low in its absence (Env₀) (blue line). For the inverse LacI variant (LacI_inv), LacZ expression level is high in the absence of IPTG (Env₀) and low in its presence (Env₁) (red line). We consider mutational trajectories from the wild type to the inverse variant (arrows).</p>", "links"=>[], "tags"=>["Biochemistry", "biophysics", "Computational biology", "ecology", "Evolutionary biology", "genetics", "microbiology", "systems biology", "schematic", "variants"], "article_id"=>733607, "categories"=>["Physics", "Biological Sciences"], "users"=>["Marjon G. J. de Vos", "Frank J. Poelwijk", "Nico Battich", "Joseph D. T. Ndika", "Sander J. Tans"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003580.g001", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Functional_description_and_schematic_representation_of_genetic_variants_in_the_lac_system_/733607", "title"=>"Functional description and schematic representation of genetic variants in the <i>lac</i> system.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-27 03:13:50"}
• {"files"=>["https://ndownloader.figshare.com/files/1103761"], "description"=>"<p>A) Schematic representation of the effect of mutations on phenotype in two environments. Mutations are represented as vectors with the start in the origin of the coordinate system. Mutations are either beneficial in both environments, Env₀ and Env₁ (quadrant I), beneficial in one environment but deleterious in the other (quadrant II or IV) or deleterious in both environments (quadrant III). Classification of interactions between two mutations in two environments: B) Opposite sides of the polygon represent the same mutation in different genetic backgrounds (a to A (red) in background b or B, and b to B in background a or A (blue)). Absence of epistasis or genotype x environment (GxE) interactions. The vectors of opposing sides are positioned in either quadrant I or III, and the polygon is a simple parallelogram, in the absence of magnitude epistasis. C) Genotype x environment interactions. Opposing sides of the parallelogram are located in the same quadrant. At least one pair of opposing sides lies in quadrant II or IV. D) Sign epistasis. Here, mutation b to B changes sign depending on the genetic background (a or A) in both environments. E) Higher-order GxGxE interactions. At least one pair of vectors from opposing sides of the polygon are located in different quadrants of which at least one vector is located in quadrant II or IV. Note however, that the presence of both GxE and GxG interactions not necessarily implies the presence of GxGxE interactions. In the case that one mutation displays sign epistasis, and the other mutation GxE, their combination does not imply GxGxE (<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003580#pgen.1003580.s001\" target=\"_blank\">Figure S1</a>).</p>", "links"=>[], "tags"=>["Biochemistry", "biophysics", "Computational biology", "ecology", "Evolutionary biology", "genetics", "microbiology", "systems biology", "higher", "genotype-environment"], "article_id"=>733608, "categories"=>["Physics", "Biological Sciences"], "users"=>["Marjon G. J. de Vos", "Frank J. Poelwijk", "Nico Battich", "Joseph D. T. Ndika", "Sander J. Tans"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003580.g002", "stats"=>{"downloads"=>2, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_higher_order_genotype_environment_interactions_/733608", "title"=>"Analysis of higher order genotype-environment interactions.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-27 03:13:50"}
• {"files"=>["https://ndownloader.figshare.com/files/1103764"], "description"=>"<p>The genetic interactions are indicated for three inverse LacI variants. Each row details the interactions between two mutations, each indicated by an X, either in a LacI_wt background (denoted by a ○), or a single mutant background (denoted by a •). We consider three types of interactions: M, magnitude epistasis; S, sign epistasis; R, reciprocal sign epistasis. The mutation that changes sign is indicated between brackets. The data shows that most genetic interactions display different types of epistasis in each of the two environments. The significance of the phenotypic effect of mutations in LacI is tested with a <i>t</i>-test in conjunction with a Bonferroni correction for multiple comparisons (<i>P</i><0.05).</p>", "links"=>[], "tags"=>["Biochemistry", "biophysics", "Computational biology", "ecology", "Evolutionary biology", "genetics", "microbiology", "systems biology", "interactions"], "article_id"=>733611, "categories"=>["Physics", "Biological Sciences"], "users"=>["Marjon G. J. de Vos", "Frank J. Poelwijk", "Nico Battich", "Joseph D. T. Ndika", "Sander J. Tans"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003580.t001", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genetic_interactions_and_their_environmental_dependence_/733611", "title"=>"Genetic interactions and their environmental dependence.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-27 03:13:50"}
• {"files"=>["https://ndownloader.figshare.com/files/1103763"], "description"=>"<p>Expression along mutational trajectories towards all three LacI_inv variants. A) (Expression)⁻¹ in Env₁ along all trajectories. B) Expression in Env₀ along all trajectories. For all three inverse variants, expression in Env₀ increases for nearly all mutational steps, in contrast to the more erratic pattern in Env₁ .</p>", "links"=>[], "tags"=>["Biochemistry", "biophysics", "Computational biology", "ecology", "Evolutionary biology", "genetics", "microbiology", "systems biology"], "article_id"=>733610, "categories"=>["Physics", "Biological Sciences"], "users"=>["Marjon G. J. de Vos", "Frank J. Poelwijk", "Nico Battich", "Joseph D. T. Ndika", "Sander J. Tans"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003580.g004", "stats"=>{"downloads"=>0, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mutational_effects_on_expression_in_both_environments_/733610", "title"=>"Mutational effects on expression in both environments.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-27 03:13:50"}

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Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[269, 466, 588, 697, 800, 896, 988, 1076, 1165, 1254, 1340, 1417]}, {"subject_area"=>"/Biology and life sciences/Genetics", "average_usage"=>[284, 491, 620, 738, 843, 945, 1043, 1137, 1225, 1315, 1400, 1479, 1555]}, {"subject_area"=>"/Physical sciences", "average_usage"=>[254, 431, 547, 651, 748, 842, 932, 1017, 1098, 1178, 1259, 1336, 1404]}, {"subject_area"=>"/Physical sciences/Physics", "average_usage"=>[254, 421, 527, 626, 720, 813, 900, 983, 1063, 1136, 1210, 1283, 1342]}]}

F1000Prime