Patterns of Evolutionary Conservation of Essential Genes Correlate with Their Compensability
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{"title"=>"Patterns of evolutionary conservation of essential genes correlate with their compensability", "type"=>"journal", "authors"=>[{"first_name"=>"Tobias", "last_name"=>"Bergmiller", "scopus_author_id"=>"9843140100"}, {"first_name"=>"Martin", "last_name"=>"Ackermann", "scopus_author_id"=>"7102624615"}, {"first_name"=>"Olin K.", "last_name"=>"Silander", "scopus_author_id"=>"14520637000"}], "year"=>2012, "source"=>"PLoS Genetics", "identifiers"=>{"pmid"=>"22761596", "doi"=>"10.1371/journal.pgen.1002803", "sgr"=>"84864052594", "isbn"=>"1553-7404 (Electronic)\\r1553-7390 (Linking)", "scopus"=>"2-s2.0-84864052594", "issn"=>"15537390", "pui"=>"365284215"}, "id"=>"eda8e088-1b32-3e68-9a96-39ac9e83bbd9", "abstract"=>"In any given organism, a fraction of all genes in the genome are required for viability; if they are experimentally deleted, the organism dies. Interestingly, the set of essential genes is usually not identical even for closely related organisms. Genes that are essential in one organism are sometimes nonessential in sister taxa or even missing from their genomes. This suggests that, in the course of evolution, some genes can be rendered non-essential and consequently can be lost. How can genes become non-essential? It is possible that changes in an organism's living conditions render previously essential functions unessential. Alternatively, it is possible that, during evolution, the function of an essential gene can be taken over by another gene, so that the essential gene becomes dispensable. Here, we tested the second hypothesis experimentally in the laboratory. We tried to replace the functions of essential genes in the bacterium Escherichia coli. We find that the genes that can easily be replaced in the laboratory are also more likely to be lost in the course of evolution. This suggests that differences in the evolutionary fate between essential genes can be partially explained by how easily their functions can be taken over by other genes.", "link"=>"http://www.mendeley.com/research/patterns-evolutionary-conservation-essential-genes-correlate-compensability", "reader_count"=>89, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>18, "Student > Doctoral Student"=>7, "Student > Ph. D. Student"=>27, "Student > Postgraduate"=>1, "Student > Master"=>19, "Other"=>5, "Student > Bachelor"=>5, "Lecturer"=>2, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>18, "Student > Doctoral Student"=>7, "Student > Ph. D. Student"=>27, "Student > Postgraduate"=>1, "Student > Master"=>19, "Other"=>5, "Student > Bachelor"=>5, "Lecturer"=>2, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>12, "Agricultural and Biological Sciences"=>65, "Medicine and Dentistry"=>1, "Philosophy"=>1, "Chemistry"=>2, "Computer Science"=>3, "Immunology and Microbiology"=>2, "Linguistics"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Chemistry"=>{"Chemistry"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>65}, "Computer Science"=>{"Computer Science"=>3}, "Linguistics"=>{"Linguistics"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>12}, "Unspecified"=>{"Unspecified"=>2}, "Philosophy"=>{"Philosophy"=>1}}, "reader_count_by_country"=>{"Korea (South)"=>1, "United States"=>2, "Brazil"=>2, "France"=>1, "Chile"=>1, "Indonesia"=>1}, "group_count"=>4}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/616317"], "description"=>"<p>We gathered information on orthologous genes in nine additional taxa for which essentiality has been experimentally investigated. All genes listed are essential in <i>E.</i> coli; for each gene, the orthologue in other taxa is indicated as essential (E; white background), non-essential (N; light grey), associated with large fitness reduction (N*), or unknown (U). Cases in which there is no orthologue are indicated with an A (absent; dark grey background). For example, <i>spoT</i>, which is essential in <i>E. coli</i>, has been found to be essential in only four out of eight other taxa and is absent from one. The second column indicates the high copy suppressors that were isolated (genes for which suppressors were isolated are highlighted in light grey). In parentheses are high copy suppressors that were recovered from the screen but which were not analyzed further. A cladogram showing the evolutionary relationships of these taxa is shown at the top of the table. Abbreviations: <i>S.ty, Salmonella typhi Ty2; A.ba, Acinetobacter baylyi; C.cr, Caulobacter crescentus NA100; F.tu, Francisella tularensis U112; S.pn, Streptococcus pneumonia TIGR4; B.su, Bacillus subtilis 168; S.au, Staphylococcus aureus 8325; M.ge, Mycoplasma genitalium G37; M.pu, Mycoplasma pulmonis UAB CTIP</i>. a) No reciprocal best hit orthologue of <i>ftsK</i> exists in <i>B. subtilis</i> due to an apparent duplication (genes BSU16800 and BSU29805); neither gene is essential. b) No reciprocal best hit orthologue of <i>plsC</i> exists in <i>F. tularensis</i> due to an apparent duplication (FTN1749 and FTN1750); only FTN1749 is essential.</p>", "links"=>[], "tags"=>["suppressors", "conserved"], "article_id"=>286814, "categories"=>["Evolutionary Biology"], "users"=>["Tobias Bergmiller", "Martin Ackermann", "Olin K. Silander"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002803.g001", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Few_high_copy_suppressors_are_found_for_conserved_and_consistently_essential_genes_/286814", "title"=>"Few high copy suppressors are found for conserved and consistently essential genes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-06-28 01:53:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/616481"], "description"=>"<p>The native promoters of 23 genes or operon pairs were replaced with the arabinose-inducible <i>araBAD</i> promoter (see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002803#s3\" target=\"_blank\">Methods</a>). By shifting these mutant strains from medium with 0.1% L-arabinose to medium without L-arabinose and supplemented with 0.4% D-glucose, expression of the essential gene was repressed. In all cases this resulted in growth inhibition or severe growth defects. The gene whose native promoter was replaced is indicated on the right hand side of each row; the ancestral strain TB741 is shown at the top. In the case of <i>degS</i>, substantial growth occurs even after repression, suggesting that growth only becomes inhibited once the gene products are sufficiently depleted; this has been observed previously <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002803#pgen.1002803-Alba1\" target=\"_blank\">[19]</a>. This is also true, although to a lesser extent, for <i>spoT</i>, <i>ftsK</i>, and <i>ygjD</i>. To grow the spot plates, cultures were grown overnight in 0.1% arabinose, diluted into LB medium, and 5 µl of the indicated dilution were spotted onto plates and incubated at 37° for 10 hours. Those strains indicated with a cross were incubated for 24 hours.</p>", "links"=>[], "tags"=>["conditional", "lethal", "mutant", "strains", "arabinose", "glucose-containing", "lb", "agar"], "article_id"=>286971, "categories"=>["Evolutionary Biology"], "users"=>["Tobias Bergmiller", "Martin Ackermann", "Olin K. Silander"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002803.g002", "stats"=>{"downloads"=>1, "page_views"=>27, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Differential_colony_formation_of_conditional_lethal_mutant_strains_on_arabinose_or_glucose_containing_LB_agar_plates_/286971", "title"=>"Differential colony formation of conditional lethal mutant strains on arabinose or glucose-containing LB agar plates.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-06-28 01:56:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/616893"], "description"=>"<p>The Protein Information Resource (<a href=\"http://pir.georgetown.edu/pirwww/search/pairwise.shtml\" target=\"_blank\">http://pir.georgetown.edu/pirwww/search/pairwise.shtml</a>) was used to generate Smith-Waterman amino acid alignments and the corresponding e-values; lower e-values imply higher homology between sequences <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002803#pgen.1002803-Smith1\" target=\"_blank\">[28]</a>. MAMMOTH (Matching Molecular Models from Theory) <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002803#pgen.1002803-Ortiz1\" target=\"_blank\">[29]</a> was used to generate pairwise structural alignments; a value above 4.5 (p = 0.01) indicates significant structural homology <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002803#pgen.1002803-Ortiz1\" target=\"_blank\">[29]</a>; if no structure was available, a structure model from <a href=\"http://modbase.compbio.ucsf.edu/modbase-cgi/index.cgi\" target=\"_blank\">http://modbase.compbio.ucsf.edu/modbase-cgi/index.cgi</a> was used. Essential genes that could be knocked out in the presence of their HCS are indicated with an asterisk.</p>", "links"=>[], "tags"=>["homology", "genes"], "article_id"=>287390, "categories"=>["Evolutionary Biology"], "users"=>["Tobias Bergmiller", "Martin Ackermann", "Olin K. Silander"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002803.t002", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Sequence_and_structural_homology_of_essential_genes_and_their_high_copy_suppressors_/287390", "title"=>"Sequence and structural homology of essential genes and their high copy suppressors.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-06-28 02:03:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/616845"], "description"=>"<p>The strains in which we were able to knockout the essential genes were grown in the presence of their respective HCS and the growth yields after 7.5 hours of growth were measured using optical density (OD) at 600 nm. The <i>dapA</i> knockout complemented with <i>nanA</i> exhibited nearly undetectable growth at all levels, suggesting that this complementation is very weak. All other mutants exhibited significantly increased yields at 50 µM IPTG, and near maximal growth yields at 500 µm IPTG. For <i>pyrH</i> and <i>spoT</i>, growth in 0 µM IPTG presumably results from leaky expression from P<sub>lac</sub>, or from carryover of gene products or small amounts of IPTG from the overnight growth cultures (see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002803#pgen-1002803-g003\" target=\"_blank\">Figure 3</a> and <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002803#s3\" target=\"_blank\">Methods</a>). Error bars indicate 95% confidence intervals.</p>", "links"=>[], "tags"=>["dosage", "dependence", "knockouts", "complemented"], "article_id"=>287337, "categories"=>["Evolutionary Biology"], "users"=>["Tobias Bergmiller", "Martin Ackermann", "Olin K. Silander"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002803.g005", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gene_dosage_dependence_of_essential_gene_knockouts_complemented_with_high_copy_suppressors_/287337", "title"=>"Gene dosage dependence of essential gene knockouts complemented with high copy suppressors.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-06-28 02:02:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/616589"], "description"=>"<p>We attempted to knock out the essential genes in strains for which we isolated an HCS. We were successful in the four cases shown here. For each essential gene, the top row illustrates the growth that is observed when the native promoter is replaced by P<sub>ara</sub>, under permissive (0.1% arabinose) or restrictive (0.4% glucose) growth conditions. The bottom row indicates the growth that is observed when the essential gene is knocked out, under conditions in which the suppressor is not induced (0 mM IPTG) or induced (1 mM IPTG). In the absence of the HCS, almost no growth is observed under restrictive conditions. However, when the HCS is induced, robust growth is almost always observed, even in the cases in which the essential gene is knocked out. Note that the Δ<i>spoT</i> strain is complemented by the <i>mutT</i> plasmid without induction of <i>mutT</i> expression. To grow the spot plates, cultures were grown overnight in 0.1% arabinose with 15 µg/ml chloramphenicol and 1 mM IPTG, diluted into LB medium, and 5 µl of the indicated dilution were spotted onto plates containing 0.1% arabinose with 15 µg/ml chloramphenicol, or 0.4% glucose with 1 mM IPTG. Arabinose plates were incubated for 14 hours at 37°, while glucose plates were incubated for 40 hours.</p>", "links"=>[], "tags"=>["knockout", "mutant"], "article_id"=>287089, "categories"=>["Evolutionary Biology"], "users"=>["Tobias Bergmiller", "Martin Ackermann", "Olin K. Silander"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002803.g003", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Differential_colony_formation_of_essential_gene_knockout_mutant_strains_/287089", "title"=>"Differential colony formation of essential gene knockout mutant strains.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-06-28 01:58:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/616724"], "description"=>"<p>In six cases we isolated HCS, but were unable to knockout the corresponding essential gene even in the presence of the HCS. For each essential gene, the top row illustrates the growth that is observed when the native promoter is replaced by P<sub>ara</sub>, under permissive (0.1% arabinose) or restrictive (0.4% glucose) conditions. The bottom row indicates the growth observed for the same strain containing the plasmid with the corresponding HCS, under permissive (0.1% arabinose) or restrictive (0.4% glucose) conditions. Expression of the HCS was induced with 50 µM IPTG. When expression of the essential gene is repressed, robust growth is only observed in the presence of the high copy suppressor. To grow the spot plates, cultures were grown overnight in 0.1% arabinose with 15 µg/ml chloramphenicol, diluted into LB medium, and 5 µl of the indicated dilution were spotted onto plates containing either 0.1% arabinose, or 0.4% glucose with 50 µM IPTG. The arabinose plates were incubated for 24 hours, while the glucose IPTG plates were incubated for 48 hours at 37°, except for P<sub>ara</sub>-<i>degS</i>, which was incubated for 14 hours.</p>", "links"=>[], "tags"=>["conditional", "lethal", "mutant", "strains", "suppressive"], "article_id"=>287214, "categories"=>["Evolutionary Biology"], "users"=>["Tobias Bergmiller", "Martin Ackermann", "Olin K. Silander"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002803.g004", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Differential_colony_formation_of_conditional_lethal_mutant_strains_with_suppressive_plasmids_/287214", "title"=>"Differential colony formation of conditional lethal mutant strains with suppressive plasmids.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-06-28 02:00:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/616921"], "description"=>"<p>We derived depletion phenotypes of conditional lethal mutants and the original function of high copy suppressor genes from literature. Proposed modes of action of the high copy suppressor genes are also based on evidence from literature.</p>", "links"=>[], "tags"=>["similarities", "non-complementing", "suppressors"], "article_id"=>287411, "categories"=>["Evolutionary Biology"], "users"=>["Tobias Bergmiller", "Martin Ackermann", "Olin K. Silander"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002803.t001", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Possible_functional_similarities_between_non_complementing_high_copy_suppressors_and_essential_genes_/287411", "title"=>"Possible functional similarities between non-complementing high copy suppressors and essential genes.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-06-28 02:03:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/321101", "https://ndownloader.figshare.com/files/321132", "https://ndownloader.figshare.com/files/321187", "https://ndownloader.figshare.com/files/321229", "https://ndownloader.figshare.com/files/321266", "https://ndownloader.figshare.com/files/321322", "https://ndownloader.figshare.com/files/321395"], "description"=>"<div><p>Essential genes code for fundamental cellular functions required for the viability of an organism. For this reason, essential genes are often highly conserved across organisms. However, this is not always the case: orthologues of genes that are essential in one organism are sometimes not essential in other organisms or are absent from their genomes. This suggests that, in the course of evolution, essential genes can be rendered nonessential. How can a gene become non-essential? Here we used genetic manipulation to deplete the products of 26 different essential genes in <em>Escherichia coli</em>. This depletion results in a lethal phenotype, which could often be rescued by the overexpression of a non-homologous, non-essential gene, most likely through replacement of the essential function. We also show that, in a smaller number of cases, the essential genes can be fully deleted from the genome, suggesting that complete functional replacement is possible. Finally, we show that essential genes whose function can be replaced in the laboratory are more likely to be non-essential or not present in other taxa. These results are consistent with the notion that patterns of evolutionary conservation of essential genes are influenced by their compensability—that is, by how easily they can be functionally replaced, for example through increased expression of other genes.</p> </div>", "links"=>[], "tags"=>["patterns", "evolutionary", "genes", "correlate", "compensability"], "article_id"=>123359, "categories"=>["Evolutionary Biology"], "users"=>["Tobias Bergmiller", "Martin Ackermann", "Olin K. Silander"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1002803.s001", "https://dx.doi.org/10.1371/journal.pgen.1002803.s002", "https://dx.doi.org/10.1371/journal.pgen.1002803.s003", "https://dx.doi.org/10.1371/journal.pgen.1002803.s004", "https://dx.doi.org/10.1371/journal.pgen.1002803.s005", "https://dx.doi.org/10.1371/journal.pgen.1002803.s006", "https://dx.doi.org/10.1371/journal.pgen.1002803.s007"], "stats"=>{"downloads"=>22, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Patterns_of_Evolutionary_Conservation_of_Essential_Genes_Correlate_with_Their_Compensability/123359", "title"=>"Patterns of Evolutionary Conservation of Essential Genes Correlate with Their Compensability", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-06-28 00:55:59"}

PMC Usage Stats | Further Information

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Relative Metric

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