-
Články
- Časopisy
- Kurzy
- Témy
- Kongresy
- Videa
- Podcasty
Mutations in Global Regulators Lead to Metabolic Selection during Adaptation to Complex Environments
Changing environmental conditions are the norm in biology. However, understanding adaptation to complex environments presents many challenges. For example, adaptation to resource-rich environments can potentially have many successful evolutionary trajectories to increased fitness. Even in conditions of plenty, the utilization of numerous but novel resources can require multiple mutations before a benefit is accrued. We evolved two bacterial species isolated from the gut of healthy humans in two different, resource-rich media commonly used in the laboratory. We anticipated that under weak selection the population would evolve tremendous genetic diversity. Despite such a complex genetic background we were able to identify a strong degree of parallel evolution and using a combination of population proteomic and population genomic approaches we show that two global regulators, arcA and rpoS, are the principle targets of selection. Up-regulation of the different metabolic pathways that are controlled by these global regulators in combination with up-regulation of transporters that transport nutrients into the cell revealed increased use of the novel resources. Thus global regulators can provide a one-step model to shift metabolism efficiently and provide rapid a one-step reprogramming of the cell metabolic profile.
Vyšlo v časopise: Mutations in Global Regulators Lead to Metabolic Selection during Adaptation to Complex Environments. PLoS Genet 10(12): e32767. doi:10.1371/journal.pgen.1004872
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004872Souhrn
Changing environmental conditions are the norm in biology. However, understanding adaptation to complex environments presents many challenges. For example, adaptation to resource-rich environments can potentially have many successful evolutionary trajectories to increased fitness. Even in conditions of plenty, the utilization of numerous but novel resources can require multiple mutations before a benefit is accrued. We evolved two bacterial species isolated from the gut of healthy humans in two different, resource-rich media commonly used in the laboratory. We anticipated that under weak selection the population would evolve tremendous genetic diversity. Despite such a complex genetic background we were able to identify a strong degree of parallel evolution and using a combination of population proteomic and population genomic approaches we show that two global regulators, arcA and rpoS, are the principle targets of selection. Up-regulation of the different metabolic pathways that are controlled by these global regulators in combination with up-regulation of transporters that transport nutrients into the cell revealed increased use of the novel resources. Thus global regulators can provide a one-step model to shift metabolism efficiently and provide rapid a one-step reprogramming of the cell metabolic profile.
Zdroje
1. LandeR (1983) The Response to Selection on Major and Minor Mutations Affecting a Metrical Trait. Heredity 50 : 47–65.
2. CooperVS, LenskiRE (2000) The population genetics of ecological specialization in evolving Escherichia coli populations. Nature 407 : 736–739.
3. LeibyN, MarxCJ (2014) Metabolic erosion primarily through mutation accumulation, and not tradeoffs, drives limited evolution of substrate specificity in Escherichia coli. PLoS Biol 12: e1001789.
4. PengL, ShimizuK (2003) Global metabolic regulation analysis for Escherichia coli K12 based on protein expression by 2-dimensional electrophoresis and enzyme activity measurement. Appl Microbiol Biotechnol 61 : 163–178.
5. FutuymaDJ, MorenoG (1988) The Evolution of Ecological Specialization. Annual Review of Ecology and Systematics 19 : 207–233.
6. BarrickJE, LenskiRE (2009) Genome-wide mutational diversity in an evolving population of Escherichia coli. Cold Spring Harbor symposia on quantitative biology 74 : 119–129.
7. ElenaSF, LenskiRE (2003) Evolution experiments with microorganisms: The dynamics and genetic bases of adaptation. Nature Reviews Genetics 4 : 457–469.
8. LenskiRE, RoseMR, SimpsonSC, TadlerSC (1991) Long-term experimental evolution in Escherichia coli I: Adaptation and divergence during 2,000 generations. American Naturalist 138 : 1315–1341.
9. LenskiRE, TravisanoM (1994) Dynamics of adaptation and diversification: A 10,000-generation experiment with bacterial populations. Proceedings of the National Academy of Sciences of the United States of America 91 : 6808–6814.
10. SaxerG, DoebeliM, TravisanoM (2009) Spatial structure leads to ecological breakdown and loss of diversity. Proceedings of the Royal Society B-Biological Sciences 276 : 2065–2070.
11. SaxerG, DoebeliM, TravisanoM (2010) The Repeatability of Adaptive Radiation During Long - Term Experimental Evolution of Escherichia coli in a Multiple Nutrient Environment Plos One. 5: e14184.
12. MillerC, KongJY, TranTT, AriasCA, SaxerG, et al. (2013) Adaptation of Enterococcus faecalis to Daptomycin Reveals an Ordered Progression to Resistance. Antimicrobial Agents and Chemotherapy 57 : 5373–5383.
13. ToprakE, VeresA, MichelJB, ChaitR, HartlDL, et al. (2012) Evolutionary paths to antibiotic resistance under dynamically sustained drug selection. Nature Genetics 44 : 101–U140.
14. CounagoR, WilsonCJ, PenaMI, Wittung-StafshedeP, ShamooY (2008) An adaptive mutation in adenylate kinase that increases organismal fitness is linked to stability-activity trade-offs. Protein Engineering Design & Selection 21 : 19–27.
15. TenaillonO, Rodriguez-VerdugoA, GautRL, McDonaldP, BennettAF, et al. (2012) The Molecular Diversity of Adaptive Convergence. Science 335 : 457–461.
16. ChouHH, ChiuHC, DelaneyNF, SegreD, MarxCJ (2011) Diminishing Returns Epistasis Among Beneficial Mutations Decelerates Adaptation. Science 332 : 1190–1192.
17. KhanAI, DinhDM, SchneiderD, LenskiRE, CooperTF (2011) Negative Epistasis Between Beneficial Mutations in an Evolving Bacterial Population. Science 332 : 1193–1196.
18. WiserMJ, RibeckN, LenskiRE (2013) Long-Term Dynamics of Adaptation in Asexual Populations. Science 342 : 1364–1367.
19. FriesenML, SaxerG, TravisanoM, DoebeliM (2004) Experimental evidence for sympatric ecological diversification due to frequency-dependent competition in Escherichia coli. Evolution 58 : 245–260.
20. SpencerCC, SaxerG, TravisanoM, DoebeliM (2007) Seasonal resource oscillations maintain diversity in bacterial microcosms. Evolutionary Ecology Research 9 : 775–787.
21. HellingRB, VargasCN, AdamsJ (1987) Evolution of Escherichia coli during growth in a constant environment. Genetics 116 : 349–358.
22. RosenzweigRF, SharpRR, TrevesDS, AdamsJ (1994) Microbial evolution in a simple unstructured environment: Genetic differentiation in Escherichia coli. Genetics 137 : 903–917.
23. StewartFM, LevinBR (1973) Partitioning of resources and outcome of interspecific competition: Model and some general considerations. American Naturalist 107 : 171–198.
24. HabetsMGJL, RozenDE, HoekstraRF, de VisserJAGM (2006) The effect of population structure on the adaptive radiation of microbial populations evolving in spatially structured environments. Ecology Letters 9 : 1041–1048.
25. RozenDE, LenskiRE (2000) Long-term experimental evolution in Escherichia coli VIII: Dynamics of a balanced polymorphism. American Naturalist 155 : 24–35.
26. RaineyPB, TravisanoM (1998) Adaptive radiation in a heterogeneous environment. Nature 394 : 69–72.
27. RundleHD, NagelL, BoughmanJW, SchluterD (2000) Natural selection and parallel speciation in sympatric sticklebacks. Science 287 : 306–308.
28. LososJB, JackmanTR, LarsonA, de QueirozK, Rodriguez-SchettinoL (1998) Contingency and determinism in replicated adaptive radiations of island lizards. Science 279 : 2115–2118.
29. BattestiA, MajdalaniN, GottesmanS (2011) The RpoS-Mediated General Stress Response in Escherichia coli. Annual Review of Microbiology Vol 65 65 : 189–213.
30. Notley-McRobbL, SeetoS, FerenciT (2003) The influence of cellular physiology on the initiation of mutational pathways in Escherichia coli populations. Proceedings of the Royal Society B-Biological Sciences 270 : 843–848.
31. BlankD, WolfL, AckermannM, SilanderOK (2014) The predictability of molecular evolution during functional innovation. Proc Natl Acad Sci U S A 111 : 3044–3049.
32. MaharjanR, SeetoS, Notley-McRobbL, FerenciT (2006) Clonal adaptive radiation in a constant environment. Science 313 : 514–517.
33. EydallinG, RyallB, MaharjanR, FerenciT (2013) The nature of laboratory domestication chagnes in freshly isolated Escherichia coli strains. Environmental Microbiology 16 : 611–905.
34. FerenciT (2005) Maintaining a healthy SPANC balance through regulatory and mutational adaptation. Molecular Microbiology 57 : 1–8.
35. BjedovI, TenaillonO, GerardB, SouzaV, DenamurE, et al. (2003) Stress-induced mutagenesis in bacteria. Science 300 : 1404–1409.
36. Al MamunAM, LombardoMJ, SheeC, LisewskiAM, GonzalezC, et al. (2012) Identity and Function of a Large Gene Network Underlying Mutagenic Repair of DNA Breaks. Science 338 : 1344–1348.
37. FinkelSE (2006) Long-term survival during stationary phase: evolution and the GASP phenotype. Nature Reviews Microbiology 4 : 113–120.
38. SnyderE, GordonDM, StoebelDM (2012) Escherichia coli Lacking RpoS Are Rare in Natural Populations of Non-Pathogens. G3-Genes Genomes Genetics 2 : 1341–1344.
39. KingT, IshihamaA, KoriA, FerenciT (2004) A regulatory trade-off as a source of strain variation in the species Escherichia coli. Journal of Bacteriology 186 : 5614–5620.
40. Puentes-TellezPE, HansenMA, SorensenSJ, van ElsasJD (2013) Adaptation and heterogeneity of Escherichia coli MC1000 growing in complex environments. Applied and environmental microbiology 79 : 1008–1017.
41. Maltby R, Leatham-Jensen MP, Gibson T, Cohen PS, Conway T (2013) Nutritional Basis for Colonization Resistance by Human Commensal Escherichia coli Strains HS and Nissle 1917 against E. coli O157:H7 in the Mouse Intestine. Plos One 8.
42. ToppingDL, CliftonPM (2001) Short-chain fatty acids and human colonic function: Roles of resistant starch and nonstarch polysaccharides. Physiological Reviews 81 : 1031–1064.
43. LynchM (2010) Evolution of the mutation rate. Trends in Genetics 26 : 345–352.
44. Saxer G, Havlak P, Fox SA, Quance MA, Gupta S, et al. (2012) Whole Genome Sequencing of Mutation Accumulation Lines Reveals a Low Mutation Rate in the Social Amoeba Dictyostelium discoideum. Plos One 7.
45. Halligan DL, Keightley PD (2009) Spontaneous mutation accumulation studies in evolutionary genetics. Annual Review of Ecology Evolution and Systematics 40.
46. PlotkinJB, KudlaG (2011) Synonymous but not the same: the causes and consequences of codon bias. Nature Reviews Genetics 12 : 32–42.
47. AnderssonSGE, KurlandCG (1990) Codon Preferences in Free-Living Microorganisms. Microbiological Reviews 54 : 198–210.
48. Hengge-Aronis R (2002) Signal transduction and regulatory mechanisms involved in control of the sigma(S) (RpoS) subunit of RNA polymerase. Microbiol Mol Biol Rev 66: : 373–395, table of contents.
49. ParkDM, AkhtarMS, AnsariAZ, LandickR, KileyPJ (2013) The bacterial response regulator ArcA uses a diverse binding site architecture to regulate carbon oxidation globally. PLoS Genet 9: e1003839.
50. Shimizu K (2013) Metabolic Regulation of a Bacterial Cell System with Emphasis on Escherichia coli Metabolism. ISRN Biochemistry 2013.
51. LevanonSS, SanKY, BennettGN (2005) Effect of oxygen on the Escherichia coli ArcA and FNR regulation systems and metabolic responses. Biotechnology and Bioengineering 89 : 556–564.
52. Herron MD, Doebeli M (2013) Parallel Evolutionary Dynamics of Adaptive Diversification in Escherichia coli. PloS Biology 11.
53. CooperTF, RozenDE, LenskiRE (2003) Parallel changes in qene expression after 20,000 generations of evolution in Escherichia coli. Proceedings of the National Academy of Sciences of the United States of America 100 : 1072–1077.
54. PerrenoudA, SauerU (2005) Impact of global transcriptional regulation by ArcA, ArcB, Cra, Crp, Cya, Fnr, and Mlc on glucose catabolism in Escherichia coli. Journal of Bacteriology 187 : 3171–3179.
55. AmaralL, MartinsA, SpenglerG, MolnarJ (2014) Efflux pumps of Gram-negative bacteria: what they do, how they do it, with what and how to deal with them. Front Pharmacol 4 : 168.
56. TaborCW, TaborH (1985) Polyamines in microorganisms. Microbiol Rev 49 : 81–99.
57. IuchiS, LinEC (1992) Purification and phosphorylation of the Arc regulatory components of Escherichia coli. J Bacteriol 174 : 5617–5623.
58. GeorgellisD, KwonO, De WulfP, LinEC (1998) Signal decay through a reverse phosphorelay in the Arc two-component signal transduction system. J Biol Chem 273 : 32864–32869.
59. Toro-RomanA, MackTR, StockAM (2005) Structural analysis and solution studies of the activated regulatory domain of the response regulator ArcA: A symmetric dimer mediated by the alpha 4-beta 5-alpha 5 face. Journal of Molecular Biology 349 : 11–26.
60. PhilippeN, CrozatE, LenskiRE, SchneiderD (2007) Evolution of global regulatory networks during a long-term experiment with Escherichia coli. Bioessays 29 : 846–860.
61. PlucainJ, HindreT, Le GacM, TenaillonO, CruveillerS, et al. (2014) Epistasis and allele specificity in the emergence of a stable polymorphism in Escherichia coli. Science 343 : 1366–1369.
62. Puentes-TellezPE, KovacsAT, KuipersOP, van ElsasJD (2014) Comparative genomics and transcriptomics analysis of experimentally evolved Escherichia coli MC1000 in complex environments. Environmental Microbiology 16 : 856–870.
63. Neidhardt FC, Curtiss III R, Ingraham JL, Lin ECC, Low KB, et al. (1996) Escherichia coli and Salmonella: Cellular and Molecular Biology. Washington, D.C.: ASM Press.
64. BaevMV, BaevD, RadekAJ, CampbellJW (2006) Growth of Escherichia coli MG1655 on LB medium: monitoring utilization of sugars, alcohols, and organic acids with transcriptional microarrays. Applied microbiology and biotechnology 71 : 310–316.
65. BaevMV, BaevD, RadekAJ, CampbellJW (2006) Growth of Escherichia coli MG1655 on LB medium: monitoring utilization of amino acids, peptides, and nucleotides with transcriptional microarrays. Applied microbiology and biotechnology 71 : 317–322.
66. RahmanM, HasanMR, ObaT, ShimizuK (2006) Effect of rpoS gene knockout on the metabolism of Escherichia coli during exponential growth phase and early stationary phase based on gene expressions, enzyme activities and intracellular metabolite concentrations. Biotechnol Bioeng 94 : 585–595.
67. BuchJK, BoyleSM (1985) Biosynthetic arginine decarboxylase in Escherichia coli is synthesized as a precursor and located in the cell envelope. J Bacteriol 163 : 522–527.
68. TkachenkoAG, NesterovaL (2001) The role of putrescine in of oxidative stress defense genes expression regulation in Escherichia coli. Mikrobiologiia 70 : 168–173.
69. ChattopadhyayMK, TaborCW, TaborH (2009) Polyamines Are Not Required for Aerobic Growth of Escherichia coli: Preparation of a Strain with Deletions in All of the Genes for Polyamine Biosynthesis. Journal of Bacteriology 191 : 5549–5552.
70. SchneiderBL, HernandezVJ, ReitzerL (2013) Putrescine catabolism is a metabolic response to several stresses in Escherichia coli. Mol Microbiol 88 : 537–550.
71. SturgillG, RatherPN (2004) Evidence that putrescine acts as an extracellular signal required for swarming in Proteus mirabilis. Mol Microbiol 51 : 437–446.
72. BernierSP, LetoffeS, DelepierreM, GhigoJM (2011) Biogenic ammonia modifies antibiotic resistance at a distance in physically separated bacteria. Mol Microbiol 81 : 705–716.
73. ReitzerL (2003) Nitrogen assimilation and global regulation in Escherichia coli. Annual Review of Microbiology 57 : 155–176.
74. WalkiewiczK, CardenasASB, SunC, BacornC, SaxerG, et al. (2012) Small changes in enzyme function can lead to surprisingly large fitness effects during adaptive evolution of antibiotic resistance. Proceedings of the National Academy of Sciences of the United States of America 109 : 21408–21413.
75. Pena MI, Davlieva M, Bennett MR, Olson JS, Shamoo Y (2010) Evolutionary fates within a microbial population highlight an essential role for protein folding during natural selection. Molecular Systems Biology 6.
76. Quance MA, Travisano M (2009) Effects of temperature on the fitness cost of resistance to bacteriophage T4 in Escherichia coli. Evolution.
77. KniesJL, IzemR, SuplerKL, KingsolverJG, BurchCL (2006) The genetic basis of thermal reaction norm evolution in lab and natural phage populations. Plos Biology 4 : 1257–1264.
78. DongT, SchellhornHE (2010) Role of RpoS in Virulence of Pathogens. Infection and Immunity 78 : 887–897.
79. SenguptaN, PaulK, ChowdhuryR (2003) The global regulator arcA modulates expression of virulence factors in Vibrio cholerae. Infection and Immunity 71 : 5583–5589.
80. Aziz RK, Bartels D, Best AA, DeJongh M, Disz T, et al. (2008) The RAST server: Rapid annotations using subsystems technology. Bmc Genomics 9.
81. OverbeekR, DiszT, StevensR (2004) The SEED: A peer-to-peer environment for genome annotation. Communications of the Acm 47 : 46–51.
82. DeatherageDE, BarrickJE (2014) Identification of Mutations in Laboratory-Evolved Microbes from Next-Generation Sequencing Data Using breseq. Methods Mol Biol 1151 : 165–188.
83. RossMG, RussC, CostelloM, HollingerA, LennonNJ, et al. (2013) Characterizing and measuring bias in sequence data. Genome Biol 14: R51.
84. LangGI, RiceDP, HickmanMJ, SodergrenE, WeinstockGM, et al. (2013) Pervasive genetic hitchhiking and clonal interference in forty evolving yeast populations. Nature 500 : 571–574.
85. Whitlock MC, Schluter D (2009) The analysis of biological data. Greenwood Village, CO: Roberts and Company Publishers.
86. ZimmerJS, MonroeME, QianWJ, SmithRD (2006) Advances in proteomics data analysis and display using an accurate mass and time tag approach. Mass Spectrom Rev 25 : 450–482.
87. PolpitiyaAD, QianWJ, JaitlyN, PetyukVA, AdkinsJN, et al. (2008) DAnTE: a statistical tool for quantitative analysis of -omics data. Bioinformatics 24 : 1556–1558.
Štítky
Genetika Reprodukčná medicína
Článek Large-scale Metabolomic Profiling Identifies Novel Biomarkers for Incident Coronary Heart DiseaseČlánek Notch Signaling Mediates the Age-Associated Decrease in Adhesion of Germline Stem Cells to the NicheČlánek Phosphorylation of Mitochondrial Polyubiquitin by PINK1 Promotes Parkin Mitochondrial TetheringČlánek Natural Variation Is Associated With Genome-Wide Methylation Changes and Temperature SeasonalityČlánek Overlapping and Non-overlapping Functions of Condensins I and II in Neural Stem Cell DivisionsČlánek Unisexual Reproduction Drives Meiotic Recombination and Phenotypic and Karyotypic Plasticity inČlánek Tetraspanin (TSP-17) Protects Dopaminergic Neurons against 6-OHDA-Induced Neurodegeneration inČlánek ABA-Mediated ROS in Mitochondria Regulate Root Meristem Activity by Controlling Expression inČlánek The Evolution of Sex Ratio Distorter Suppression Affects a 25 cM Genomic Region in the Butterfly
Článok vyšiel v časopisePLOS Genetics
Najčítanejšie tento týždeň
2014 Číslo 12- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
-
Všetky články tohto čísla
- Stratification by Smoking Status Reveals an Association of Genotype with Body Mass Index in Never Smokers
- Genome Wide Meta-analysis Highlights the Role of Genetic Variation in in the Regulation of Circulating Serum Chemerin
- Occupancy of Mitochondrial Single-Stranded DNA Binding Protein Supports the Strand Displacement Mode of DNA Replication
- Distinct Genealogies for Plasmids and Chromosome
- Large-scale Metabolomic Profiling Identifies Novel Biomarkers for Incident Coronary Heart Disease
- Non-coding RNAs Prevent the Binding of the MSL-complex to Heterochromatic Regions
- Plasmid Flux in ST131 Sublineages, Analyzed by Plasmid Constellation Network (PLACNET), a New Method for Plasmid Reconstruction from Whole Genome Sequences
- Epigenome-Guided Analysis of the Transcriptome of Plaque Macrophages during Atherosclerosis Regression Reveals Activation of the Wnt Signaling Pathway
- The Inventiveness of Nature: An Interview with Werner Arber
- Mediation Analysis Demonstrates That -eQTLs Are Often Explained by -Mediation: A Genome-Wide Analysis among 1,800 South Asians
- Generation of Antigenic Diversity in by Structured Rearrangement of Genes During Mitosis
- A Massively Parallel Pipeline to Clone DNA Variants and Examine Molecular Phenotypes of Human Disease Mutations
- Genetic Analysis of the Cardiac Methylome at Single Nucleotide Resolution in a Model of Human Cardiovascular Disease
- Genetic Analysis of Circadian Responses to Low Frequency Electromagnetic Fields in
- The Dissection of Meiotic Chromosome Movement in Mice Using an Electroporation Technique
- Altered Chromatin Occupancy of Master Regulators Underlies Evolutionary Divergence in the Transcriptional Landscape of Erythroid Differentiation
- Syd/JIP3 and JNK Signaling Are Required for Myonuclear Positioning and Muscle Function
- Notch Signaling Mediates the Age-Associated Decrease in Adhesion of Germline Stem Cells to the Niche
- Mutation of Leads to Blurred Tonotopic Organization of Central Auditory Circuits in Mice
- The IKAROS Interaction with a Complex Including Chromatin Remodeling and Transcription Elongation Activities Is Required for Hematopoiesis
- RAN-Binding Protein 9 is Involved in Alternative Splicing and is Critical for Male Germ Cell Development and Male Fertility
- Enhanced Longevity by Ibuprofen, Conserved in Multiple Species, Occurs in Yeast through Inhibition of Tryptophan Import
- Phosphorylation of Mitochondrial Polyubiquitin by PINK1 Promotes Parkin Mitochondrial Tethering
- Recurrent Loss of Specific Introns during Angiosperm Evolution
- Natural Variation Is Associated With Genome-Wide Methylation Changes and Temperature Seasonality
- SEEDSTICK is a Master Regulator of Development and Metabolism in the Arabidopsis Seed Coat
- Overlapping and Non-overlapping Functions of Condensins I and II in Neural Stem Cell Divisions
- Unisexual Reproduction Drives Meiotic Recombination and Phenotypic and Karyotypic Plasticity in
- Tetraspanin (TSP-17) Protects Dopaminergic Neurons against 6-OHDA-Induced Neurodegeneration in
- ABA-Mediated ROS in Mitochondria Regulate Root Meristem Activity by Controlling Expression in
- Mutations in Global Regulators Lead to Metabolic Selection during Adaptation to Complex Environments
- Global Analysis of Photosynthesis Transcriptional Regulatory Networks
- Mucolipin Co-deficiency Causes Accelerated Endolysosomal Vacuolation of Enterocytes and Failure-to-Thrive from Birth to Weaning
- Controlling Pre-leukemic Thymocyte Self-Renewal
- How Malaria Parasites Avoid Running Out of Ammo
- Echoes of the Past: Hereditarianism and
- Deep Reads: Strands in the History of Molecular Genetics
- Keep on Laying Eggs Mama, RNAi My Reproductive Aging Blues Away
- Analysis of a Plant Complex Resistance Gene Locus Underlying Immune-Related Hybrid Incompatibility and Its Occurrence in Nature
- Epistatic Adaptive Evolution of Human Color Vision
- Increased and Imbalanced dNTP Pools Symmetrically Promote Both Leading and Lagging Strand Replication Infidelity
- Genetic Basis of Haloperidol Resistance in Is Complex and Dose Dependent
- Genome-Wide Analysis of DNA Methylation Dynamics during Early Human Development
- Interaction between Conjugative and Retrotransposable Elements in Horizontal Gene Transfer
- The Evolution of Sex Ratio Distorter Suppression Affects a 25 cM Genomic Region in the Butterfly
- is Required for Adult Maintenance of Dopaminergic Neurons in the Ventral Substantia Nigra
- PRL1, an RNA-Binding Protein, Positively Regulates the Accumulation of miRNAs and siRNAs in Arabidopsis
- Genetic Control of Contagious Asexuality in the Pea Aphid
- Early Mesozoic Coexistence of Amniotes and Hepadnaviridae
- Local and Systemic Regulation of Plant Root System Architecture and Symbiotic Nodulation by a Receptor-Like Kinase
- Gene Pathways That Delay Reproductive Senescence
- The Evolution of Fungal Metabolic Pathways
- Maf1 Is a Novel Target of PTEN and PI3K Signaling That Negatively Regulates Oncogenesis and Lipid Metabolism
- Formation of Linear Amplicons with Inverted Duplications in Requires the MRE11 Nuclease
- Identification of Rare Causal Variants in Sequence-Based Studies: Methods and Applications to , a Gene Involved in Cohen Syndrome and Autism
- Rrp12 and the Exportin Crm1 Participate in Late Assembly Events in the Nucleolus during 40S Ribosomal Subunit Biogenesis
- The Mutations in the ATP-Binding Groove of the Rad3/XPD Helicase Lead to -Cockayne Syndrome-Like Phenotypes
- Topoisomerase I Plays a Critical Role in Suppressing Genome Instability at a Highly Transcribed G-Quadruplex-Forming Sequence
- A Cbx8-Containing Polycomb Complex Facilitates the Transition to Gene Activation during ES Cell Differentiation
- Transcriptional Frameshifting Rescues Type VI Secretion by the Production of Two Length Variants from the Prematurely Interrupted Gene
- Association Mapping across Numerous Traits Reveals Patterns of Functional Variation in Maize
- Genome-Wide Analysis of -Regulated and Phased Small RNAs Underscores the Importance of the ta-siRNA Pathway to Maize Development
- Dissemination of Cephalosporin Resistance Genes between Strains from Farm Animals and Humans by Specific Plasmid Lineages
- The Tau Tubulin Kinases TTBK1/2 Promote Accumulation of Pathological TDP-43
- Germline Signals Deploy NHR-49 to Modulate Fatty-Acid β-Oxidation and Desaturation in Somatic Tissues of
- Microevolution of in Macrophages Restores Filamentation in a Nonfilamentous Mutant
- Vangl2-Regulated Polarisation of Second Heart Field-Derived Cells Is Required for Outflow Tract Lengthening during Cardiac Development
- Chondrocytes Transdifferentiate into Osteoblasts in Endochondral Bone during Development, Postnatal Growth and Fracture Healing in Mice
- A ABC Transporter Regulates Lifespan
- RA and FGF Signalling Are Required in the Zebrafish Otic Vesicle to Pattern and Maintain Ventral Otic Identities
- , and Reprogram Thymocytes into Self-Renewing Cells
- The miR9863 Family Regulates Distinct Alleles in Barley to Attenuate NLR Receptor-Triggered Disease Resistance and Cell-Death Signaling
- Detection of Pleiotropy through a Phenome-Wide Association Study (PheWAS) of Epidemiologic Data as Part of the Environmental Architecture for Genes Linked to Environment (EAGLE) Study
- Extensive Copy-Number Variation of Young Genes across Stickleback Populations
- The and Genetic Modules Interact to Regulate Ciliogenesis and Ciliary Microtubule Patterning in
- Analysis of the Genome, Transcriptome and Secretome Provides Insight into Its Pioneer Colonization Strategies of Wood
- PLOS Genetics
- Archív čísel
- Aktuálne číslo
- Informácie o časopise
Najčítanejšie v tomto čísle- Tetraspanin (TSP-17) Protects Dopaminergic Neurons against 6-OHDA-Induced Neurodegeneration in
- Maf1 Is a Novel Target of PTEN and PI3K Signaling That Negatively Regulates Oncogenesis and Lipid Metabolism
- The IKAROS Interaction with a Complex Including Chromatin Remodeling and Transcription Elongation Activities Is Required for Hematopoiesis
- Echoes of the Past: Hereditarianism and
Prihlásenie#ADS_BOTTOM_SCRIPTS#Zabudnuté hesloZadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.
- Časopisy