-
Články
- Časopisy
- Kurzy
- Témy
- Kongresy
- Videa
- Podcasty
Intrasubtype Reassortments Cause Adaptive Amino Acid Replacements in H3N2 Influenza Genes
Reassortments and point mutations are two major contributors to diversity of Influenza A virus; however, the link between these two processes is unclear. It has been suggested that reassortments provoke a temporary increase in the rate of amino acid changes as the viral proteins adapt to new genetic environment, but this phenomenon has not been studied systematically. Here, we use a phylogenetic approach to infer the reassortment events between the 8 segments of influenza A H3N2 virus since its emergence in humans in 1968. We then study the amino acid replacements that occurred in genes encoded in each segment subsequent to reassortments. In five out of eight genes (NA, M1, HA, PB1 and NS1), the reassortment events led to a transient increase in the rate of amino acid replacements on the descendant phylogenetic branches. In NA and HA, the replacements following reassortments were enriched with parallel and/or reversing replacements; in contrast, the replacements at sites responsible for differences between antigenic clusters (in HA) and at sites under positive selection (in NA) were underrepresented among them. Post-reassortment adaptive walks contribute to adaptive evolution in Influenza A: in NA, an average reassortment event causes at least 2.1 amino acid replacements in a reassorted gene, with, on average, 0.43 amino acid replacements per evolving post-reassortment lineage; and at least ∼9% of all amino acid replacements are provoked by reassortments.
Vyšlo v časopise: Intrasubtype Reassortments Cause Adaptive Amino Acid Replacements in H3N2 Influenza Genes. PLoS Genet 10(1): e32767. doi:10.1371/journal.pgen.1004037
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004037Souhrn
Reassortments and point mutations are two major contributors to diversity of Influenza A virus; however, the link between these two processes is unclear. It has been suggested that reassortments provoke a temporary increase in the rate of amino acid changes as the viral proteins adapt to new genetic environment, but this phenomenon has not been studied systematically. Here, we use a phylogenetic approach to infer the reassortment events between the 8 segments of influenza A H3N2 virus since its emergence in humans in 1968. We then study the amino acid replacements that occurred in genes encoded in each segment subsequent to reassortments. In five out of eight genes (NA, M1, HA, PB1 and NS1), the reassortment events led to a transient increase in the rate of amino acid replacements on the descendant phylogenetic branches. In NA and HA, the replacements following reassortments were enriched with parallel and/or reversing replacements; in contrast, the replacements at sites responsible for differences between antigenic clusters (in HA) and at sites under positive selection (in NA) were underrepresented among them. Post-reassortment adaptive walks contribute to adaptive evolution in Influenza A: in NA, an average reassortment event causes at least 2.1 amino acid replacements in a reassorted gene, with, on average, 0.43 amino acid replacements per evolving post-reassortment lineage; and at least ∼9% of all amino acid replacements are provoked by reassortments.
Zdroje
1. KilbourneED (2006) Influenza pandemics of the 20th century. Emerging Infect Dis 12 : 9–14 doi:10.3201/eid1201.051254
2. LiC, HattaM, WatanabeS, NeumannG, KawaokaY (2008) Compatibility among polymerase subunit proteins is a restricting factor in reassortment between equine H7N7 and human H3N2 influenza viruses. J Virol 82 : 11880–11888 doi:10.1128/JVI.01445-08
3. LiC, HattaM, NidomCA, MuramotoY, WatanabeS, et al. (2010) Reassortment between avian H5N1 and human H3N2 influenza viruses creates hybrid viruses with substantial virulence. PNAS 107 : 4687–4692 doi:10.1073/pnas.0912807107
4. SuzukiY (2010) A phylogenetic approach to detecting reassortments in viruses with segmented genomes. Gene 464 : 11–16 doi:10.1016/j.gene.2010.05.002
5. NelsonMI, HolmesEC (2007) The evolution of epidemic influenza. Nature Reviews Genetics 8 : 196–205 doi:10.1038/nrg2053
6. LindstromSE, HiromotoY, NeromeR, OmoeK, SugitaS, et al. (1998) Phylogenetic analysis of the entire genome of influenza A (H3N2) viruses from Japan: evidence for genetic reassortment of the six internal genes. J Virol 72 : 8021–8031.
7. HolmesEC, GhedinE, MillerN, TaylorJ, BaoY, et al. (2005) Whole-genome analysis of human influenza A virus reveals multiple persistent lineages and reassortment among recent H3N2 viruses. PLoS Biol 3: e300 doi:10.1371/journal.pbio.0030300
8. NelsonMI, SimonsenL, ViboudC, MillerMA, TaylorJ, et al. (2006) Stochastic processes are key determinants of short-term evolution in influenza a virus. PLoS Pathog 2: e125 doi:10.1371/journal.ppat.0020125
9. NelsonMI, ViboudC, SimonsenL, BennettRT, GriesemerSB, et al. (2008) Multiple reassortment events in the evolutionary history of H1N1 influenza A virus since 1918. PLoS Pathog 4: e1000012 doi:10.1371/journal.ppat.1000012
10. RabadanR, LevineAJ, KrasnitzM (2008) Non-random reassortment in human influenza A viruses. Influenza Other Respi Viruses 2 : 9–22 doi:10.1111/j.1750-2659.2007.00030.x
11. De SilvaUC, TanakaH, NakamuraS, GotoN, YasunagaT (2012) A comprehensive analysis of reassortment in influenza A virus. Biol Open 1 : 385–390 doi:10.1242/bio.2012281
12. NagarajanN, KingsfordC (2011) GiRaF: robust, computational identification of influenza reassortments via graph mining. Nucleic Acids Res 39: e34 doi:10.1093/nar/gkq1232
13. YurovskyA, MoretBME (2011) FluReF, an automated flu virus reassortment finder based on phylogenetic trees. BMC Genomics 12: S3 doi:10.1186/1471-2164-12-S2-S3
14. SvintiV, CottonJA, McInerneyJO (2013) New approaches for unravelling reassortment pathways. BMC Evol Biol 13 : 1 doi:10.1186/1471-2148-13-1
15. LubeckMD, PaleseP, SchulmanJL (1979) Nonrandom association of parental genes in influenza A virus recombinants. Virology 95 : 269–274.
16. Downie JC (2004) Reassortment of influenza A virus genes linked to PB1 polymerase gene. In: Kawaoka Y, editor. Options for the Control of Influenza V. Amsterdam: Elsevier Science Bv, Vol. 1263. pp. 714–718.
17. VarichNL, GitelmanAK, ShilovAA, SmirnovYA, KaverinNV (2008) Deviation from the random distribution pattern of influenza A virus gene segments in reassortants produced under non-selective conditions. Arch Virol 153 : 1149–1154 doi:10.1007/s00705-008-0070-5
18. ChenL-M, DavisCT, ZhouH, CoxNJ, DonisRO (2008) Genetic Compatibility and Virulence of Reassortants Derived from Contemporary Avian H5N1 and Human H3N2 Influenza A Viruses. PLoS Pathog 4: e1000072 doi:10.1371/journal.ppat.1000072
19. GreenbaumBD, LiOTW, PoonLLM, LevineAJ, RabadanR (2012) Viral reassortment as an information exchange between viral segments. Proc Natl Acad Sci USA 109 : 3341–3346 doi:10.1073/pnas.1113300109
20. SchrauwenEJA, BestebroerTM, RimmelzwaanGF, OsterhausADME, FouchierRAM, et al. (2013) Reassortment between Avian H5N1 and Human Influenza Viruses Is Mainly Restricted to the Matrix and Neuraminidase Gene Segments. PLoS ONE 8: e59889 doi:10.1371/journal.pone.0059889
21. KhiabanianH, TrifonovV, RabadanR (2009) Reassortment Patterns in Swine Influenza Viruses. PLoS ONE 4: e7366 doi:10.1371/journal.pone.0007366
22. RambautA, PybusOG, NelsonMI, ViboudC, TaubenbergerJK, et al. (2008) The genomic and epidemiological dynamics of human influenza A virus. Nature 453 : 615–619 doi:10.1038/nature06945
23. RudnevaIA, TimofeevaTA, IlyushinaNA, VarichNL, Kochergin-NikitskyKS, et al. (2008) Post-reassortment amino acid change in the hemagglutinin of a human-avian influenza H5N1 reassortant virus alters its antigenic specificity. Acta Virol 52 : 181–184.
24. VijaykrishnaD, SmithGJD, PybusOG, ZhuH, BhattS, et al. (2011) Long-term evolution and transmission dynamics of swine influenza A virus. Nature 473 : 519–522 doi:10.1038/nature10004
25. GoldingGB (1987) The detection of deleterious selection using ancestors inferred from a phylogenetic history. Genetics Research 49 : 71–82 doi:10.1017/S0016672300026768
26. BushRM, FitchWM, BenderCA, CoxNJ (1999) Positive selection on the H3 hemagglutinin gene of human influenza virus A. Mol Biol Evol 16 : 1457–1465.
27. RochaEPC, SmithJM, HurstLD, HoldenMTG, CooperJE, et al. (2006) Comparisons of dN/dS are time dependent for closely related bacterial genomes. J Theor Biol 239 : 226–235 doi:10.1016/j.jtbi.2005.08.037
28. PybusOG, RambautA, BelshawR, FreckletonRP, DrummondAJ, et al. (2007) Phylogenetic Evidence for Deleterious Mutation Load in RNA Viruses and Its Contribution to Viral Evolution. Mol Biol Evol 24 : 845–852 doi:10.1093/molbev/msm001
29. KryazhimskiyS, BazykinGA, DushoffJ (2008) Natural selection for nucleotide usage at synonymous and nonsynonymous sites in influenza A virus genes. J Virol 82 : 4938–4945 doi:10.1128/JVI.02415-07
30. KryazhimskiyS, PlotkinJB (2008) The Population Genetics of dN/dS. PLoS Genet 4: e1000304 doi:10.1371/journal.pgen.1000304
31. GillespieJH (1984) Molecular evolution over the mutational landscape. Evolution 38 : 1116–1129.
32. KauffmanS, LevinS (1987) Towards a general theory of adaptive walks on rugged landscapes. Journal of Theoretical Biology 128 : 11–45 doi:10.1016/S0022-5193(87)80029-2
33. SmithDJ, LapedesAS, Jong JCde, BestebroerTM, RimmelzwaanGF, et al. (2004) Mapping the Antigenic and Genetic Evolution of Influenza Virus. Science 305 : 371–376 doi:10.1126/science.1097211
34. KryazhimskiyS, DushoffJ, BazykinGA, PlotkinJB (2011) Prevalence of epistasis in the evolution of influenza A surface proteins. PLoS Genet 7: e1001301 doi:10.1371/journal.pgen.1001301
35. WolfYI, ViboudC, HolmesEC, KooninEV, LipmanDJ (2006) Long intervals of stasis punctuated by bursts of positive selection in the seasonal evolution of influenza A virus. Biology Direct 1 : 34 doi:10.1186/1745-6150-1-34
36. ShihAC-C, HsiaoT-C, HoM-S, LiW-H (2007) Simultaneous amino acid substitutions at antigenic sites drive influenza A hemagglutinin evolution. Proc Natl Acad Sci USA 104 : 6283–6288 doi:10.1073/pnas.0701396104
37. Gillespie JH (1991) The Causes of Molecular Evolution. Oxford University Press. 354 p.
38. StrelkowaN, LässigM (2012) Clonal interference in the evolution of influenza. Genetics 192 : 671–682 doi:10.1534/genetics.112.143396
39. IllingworthCJR, MustonenV (2012) Components of Selection in the Evolution of the Influenza Virus: Linkage Effects Beat Inherent Selection. PLoS Pathog 8: e1003091 doi:10.1371/journal.ppat.1003091
40. FourmentM, WoodJT, GibbsAJ, GibbsMJ (2010) Evolutionary dynamics of the N1 neuraminidases of the main lineages of influenza A viruses. Mol Phylogenet Evol 56 : 526–535 doi:10.1016/j.ympev.2010.04.039
41. FuruseY, SuzukiA, OshitaniH (2010) Reassortment between swine influenza A viruses increased their adaptation to humans in pandemic H1N1/09. Infect Genet Evol 10 : 569–574 doi:10.1016/j.meegid.2010.01.010
42. RabadanR, LevineAJ, RobinsH (2006) Comparison of Avian and Human Influenza A Viruses Reveals a Mutational Bias on the Viral Genomes. J Virol 80 : 11887–11891 doi:10.1128/JVI.01414-06
43. Dos ReisM, HayAJ, GoldsteinRA (2009) Using non-homogeneous models of nucleotide substitution to identify host shift events: application to the origin of the 1918 “Spanish” influenza pandemic virus. J Mol Evol 69 : 333–345 doi:10.1007/s00239-009-9282-x
44. WongEH, SmithDK, RabadanR, PeirisM, PoonLL (2010) Codon usage bias and the evolution of influenza A viruses. Codon Usage Biases of Influenza Virus. BMC Evolutionary Biology 10 : 253 doi:10.1186/1471-2148-10-253
45. SandbulteMR, WestgeestKB, GaoJ, XuX, KlimovAI, et al. (2011) Discordant antigenic drift of neuraminidase and hemagglutinin in H1N1 and H3N2 influenza viruses. Proc Natl Acad Sci USA 108 : 20748–20753 doi:10.1073/pnas.1113801108
46. HensleySE, DasSR, GibbsJS, BaileyAL, SchmidtLM, et al. (2011) Influenza A virus hemagglutinin antibody escape promotes neuraminidase antigenic variation and drug resistance. PLoS ONE 6: e15190 doi:10.1371/journal.pone.0015190
47. MyersJL, WetzelKS, LindermanSL, LiY, SullivanCB, et al. (2013) Compensatory hemagglutinin mutations alter antigenic properties of influenza viruses. J Virol 87 : 11168–11172 doi:10.1128/JVI.01414-13
48. YurovskyA, MoretBME (2011) FluReF, an automated flu virus reassortment finder based on phylogenetic trees. BMC Genomics 12: S3 doi:10.1186/1471-2164-12-S2-S3
49. WolfYI, ViboudC, HolmesEC, KooninEV, LipmanDJ (2006) Long intervals of stasis punctuated by bursts of positive selection in the seasonal evolution of influenza A virus. Biol Direct 1 : 34 doi:10.1186/1745-6150-1-34
50. KryazhimskiyS, BazykinGA, PlotkinJ, DushoffJ (2008) Directionality in the evolution of influenza A haemagglutinin. Proc R Soc B-Biol Sci 275 : 2455–2464 doi:10.1098/rspb.2008.0521
51. RimmelzwaanGF, BerkhoffEGM, NieuwkoopNJ, FouchierRAM, OsterhausADME (2004) Functional compensation of a detrimental amino acid substitution in a cytotoxic-T-lymphocyte epitope of influenza a viruses by comutations. J Virol 78 : 8946–8949 doi:10.1128/JVI.78.16.8946-8949.2004
52. RimmelzwaanGF, BerkhoffEGM, NieuwkoopNJ, SmithDJ, FouchierRAM, et al. (2005) Full restoration of viral fitness by multiple compensatory co-mutations in the nucleoprotein of influenza A virus cytotoxic T-lymphocyte escape mutants. J Gen Virol 86 : 1801–1805 doi:10.1099/vir.0.80867-0
53. KoelleK, CobeyS, GrenfellB, PascualM (2006) Epochal Evolution Shapes the Phylodynamics of Interpandemic Influenza A (H3N2) in Humans. Science 314 : 1898–1903 doi:10.1126/science.1132745
54. ShapiroB, RambautA, PybusOG, HolmesEC (2006) A phylogenetic method for detecting positive epistasis in gene sequences and its application to RNA virus evolution. Mol Biol Evol 23 : 1724–1730 doi:10.1093/molbev/msl037
55. MitnaulLJ, MatrosovichMN, CastrucciMR, TuzikovAB, BovinNV, et al. (2000) Balanced hemagglutinin and neuraminidase activities are critical for efficient replication of influenza A virus. J Virol 74 : 6015–6020.
56. FergusonNM, FraserC, DonnellyCA, GhaniAC, AndersonRM (2004) Public Health Risk from the Avian H5N1 Influenza Epidemic. Science 304 : 968–969 doi:10.1126/science.1096898
57. YongE (2012) Influenza: Five questions on H5N1. Nature 486 : 456–458 doi:10.1038/486456a
58. ButlerD (2012) Death-rate row blurs mutant flu debate. Nature 482 : 289 doi:10.1038/482289a
59. HerfstS, SchrauwenEJA, LinsterM, ChutinimitkulS, WitEde, et al. (2012) Airborne Transmission of Influenza A/H5N1 Virus Between Ferrets. Science 336 : 1534–1541 doi:10.1126/science.1213362
60. ImaiM, WatanabeT, HattaM, DasSC, OzawaM, et al. (2012) Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets. Nature 486 : 420–428 doi:10.1038/nature10831
61. RussellCA, FonvilleJM, BrownAEX, BurkeDF, SmithDL, et al. (2012) The Potential for Respiratory Droplet–Transmissible A/H5N1 Influenza Virus to Evolve in a Mammalian Host. Science 336 : 1541–1547 doi:10.1126/science.1222526
62. BaoY, BolotovP, DernovoyD, KiryutinB, ZaslavskyL, et al. (2008) The influenza virus resource at the National Center for Biotechnology Information. J Virol 82 : 596–601 doi:10.1128/JVI.02005-07
63. EdgarRC (2004) MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 32 : 1792–1797 doi:10.1093/nar/gkh340
64. EdgarRC (2004) MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC Bioinformatics 5 : 113 doi:10.1186/1471-2105-5-113
65. LiW, GodzikA (2006) Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences. Bioinformatics 22 : 1658–1659 doi:10.1093/bioinformatics/btl158
66. HuelsenbeckJP, RonquistF (2001) MRBAYES: Bayesian inference of phylogenetic trees. Bioinformatics 17 : 754–755.
67. RonquistF, HuelsenbeckJP (2003) MrBayes 3: Bayesian phylogenetic inference under mixed models. Bioinformatics 19 : 1572–1574.
68. AltekarG, DwarkadasS, HuelsenbeckJP, RonquistF (2004) Parallel Metropolis coupled Markov chain Monte Carlo for Bayesian phylogenetic inference. Bioinformatics 20 : 407–415 doi:10.1093/bioinformatics/btg427
69. OlsenCW, KarasinAI, CarmanS, LiY, BastienN, et al. (2006) Triple reassortant H3N2 influenza A viruses, Canada, 2005. Emerging Infect Dis 12 : 1132–1135 doi:10.3201/eid1207.060268
70. PondSLK, FrostSDW, MuseSV (2005) HyPhy: hypothesis testing using phylogenies. Bioinformatics 21 : 676–679 doi:10.1093/bioinformatics/bti079
71. PondSLK (2004) A Genetic Algorithm Approach to Detecting Lineage-Specific Variation in Selection Pressure. Molecular Biology and Evolution 22 : 478–485 doi:10.1093/molbev/msi031
72. GuindonS, DelsucF, DufayardJ-F, GascuelO (2009) Estimating maximum likelihood phylogenies with PhyML. Methods Mol Biol 537 : 113–137 doi:_10.1007/978-1-59745-251-9_6
73. GrenfellBT, PybusOG, GogJR, WoodJLN, DalyJM, et al. (2004) Unifying the Epidemiological and Evolutionary Dynamics of Pathogens. Science 303 : 327–332 doi:10.1126/science.1090727
74. MurrellB, WertheimJO, MoolaS, WeighillT, SchefflerK, et al. (2012) Detecting Individual Sites Subject to Episodic Diversifying Selection. PLoS Genetics 8: e1002764 doi:10.1371/journal.pgen.1002764
75. VosRA, CaravasJ, HartmannK, JensenMA, MillerC (2011) BIO::Phylo-phyloinformatic analysis using perl. BMC Bioinformatics 12 : 63 doi:10.1186/1471-2105-12-63
76. R Development Core Team (2008) R: a language and environment for statistical computing. Vienna, Austria: R foundation for statistical computing. Available: http://www.r-project.org./. Accessed 29 May 2013.
77. ScornavaccaC, ZickmannF, HusonDH (2011) Tanglegrams for rooted phylogenetic trees and networks. Bioinformatics 27: i248–i256 doi:10.1093/bioinformatics/btr210
Štítky
Genetika Reprodukčná medicína
Článek Unwrapping BacteriaČlánek A Chaperone-Assisted Degradation Pathway Targets Kinetochore Proteins to Ensure Genome StabilityČlánek The Candidate Splicing Factor Sfswap Regulates Growth and Patterning of Inner Ear Sensory OrgansČlánek The SPF27 Homologue Num1 Connects Splicing and Kinesin 1-Dependent Cytoplasmic Trafficking inČlánek Down-Regulation of eIF4GII by miR-520c-3p Represses Diffuse Large B Cell Lymphoma DevelopmentČlánek Meta-Analysis Identifies Gene-by-Environment Interactions as Demonstrated in a Study of 4,965 MiceČlánek High Risk Population Isolate Reveals Low Frequency Variants Predisposing to Intracranial Aneurysms
Článok vyšiel v časopisePLOS Genetics
Najčítanejšie tento týždeň
2014 Číslo 1- 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
- How Much Is That in Dog Years? The Advent of Canine Population Genomics
- The Sense and Sensibility of Strand Exchange in Recombination Homeostasis
- Unwrapping Bacteria
- DNA Methylation Changes Separate Allergic Patients from Healthy Controls and May Reflect Altered CD4 T-Cell Population Structure
- Evidence for Mito-Nuclear and Sex-Linked Reproductive Barriers between the Hybrid Italian Sparrow and Its Parent Species
- Translation Enhancing ACA Motifs and Their Silencing by a Bacterial Small Regulatory RNA
- Relationship Estimation from Whole-Genome Sequence Data
- Genetic Models of Apoptosis-Induced Proliferation Decipher Activation of JNK and Identify a Requirement of EGFR Signaling for Tissue Regenerative Responses in
- ComEA Is Essential for the Transfer of External DNA into the Periplasm in Naturally Transformable Cells
- Loss and Recovery of Genetic Diversity in Adapting Populations of HIV
- Bioelectric Signaling Regulates Size in Zebrafish Fins
- Defining NELF-E RNA Binding in HIV-1 and Promoter-Proximal Pause Regions
- Loss of Histone H3 Methylation at Lysine 4 Triggers Apoptosis in
- Cell-Cycle Dependent Expression of a Translocation-Mediated Fusion Oncogene Mediates Checkpoint Adaptation in Rhabdomyosarcoma
- How a Retrotransposon Exploits the Plant's Heat Stress Response for Its Activation
- A Nonsense Mutation in Encoding a Nondescript Transmembrane Protein Causes Idiopathic Male Subfertility in Cattle
- Deletion of a Conserved -Element in the Locus Highlights the Role of Acute Histone Acetylation in Modulating Inducible Gene Transcription
- Developmental Link between Sex and Nutrition; Regulates Sex-Specific Mandible Growth via Juvenile Hormone Signaling in Stag Beetles
- PP2A/B55 and Fcp1 Regulate Greatwall and Ensa Dephosphorylation during Mitotic Exit
- Differential Effects of Collagen Prolyl 3-Hydroxylation on Skeletal Tissues
- Comprehensive Functional Annotation of 77 Prostate Cancer Risk Loci
- Evolution of Chloroplast Transcript Processing in and Its Chromerid Algal Relatives
- A Chaperone-Assisted Degradation Pathway Targets Kinetochore Proteins to Ensure Genome Stability
- New MicroRNAs in —Birth, Death and Cycles of Adaptive Evolution
- A Genome-Wide Screen for Bacterial Envelope Biogenesis Mutants Identifies a Novel Factor Involved in Cell Wall Precursor Metabolism
- FGFR1-Frs2/3 Signalling Maintains Sensory Progenitors during Inner Ear Hair Cell Formation
- Regulation of Synaptic /Neuroligin Abundance by the /Nrf Stress Response Pathway Protects against Oxidative Stress
- Intrasubtype Reassortments Cause Adaptive Amino Acid Replacements in H3N2 Influenza Genes
- Molecular Specificity, Convergence and Constraint Shape Adaptive Evolution in Nutrient-Poor Environments
- WNT7B Promotes Bone Formation in part through mTORC1
- Natural Selection Reduced Diversity on Human Y Chromosomes
- In-Vivo Quantitative Proteomics Reveals a Key Contribution of Post-Transcriptional Mechanisms to the Circadian Regulation of Liver Metabolism
- The Candidate Splicing Factor Sfswap Regulates Growth and Patterning of Inner Ear Sensory Organs
- The Acid Phosphatase-Encoding Gene Contributes to Soybean Tolerance to Low-Phosphorus Stress
- p53 and TAp63 Promote Keratinocyte Proliferation and Differentiation in Breeding Tubercles of the Zebrafish
- Affects Plant Architecture by Regulating Local Auxin Biosynthesis
- The SET Domain Proteins SUVH2 and SUVH9 Are Required for Pol V Occupancy at RNA-Directed DNA Methylation Loci
- Down-Regulation of Rad51 Activity during Meiosis in Yeast Prevents Competition with Dmc1 for Repair of Double-Strand Breaks
- Multi-tissue Analysis of Co-expression Networks by Higher-Order Generalized Singular Value Decomposition Identifies Functionally Coherent Transcriptional Modules
- A Neurotoxic Glycerophosphocholine Impacts PtdIns-4, 5-Bisphosphate and TORC2 Signaling by Altering Ceramide Biosynthesis in Yeast
- Subtle Changes in Motif Positioning Cause Tissue-Specific Effects on Robustness of an Enhancer's Activity
- C/EBPα Is Required for Long-Term Self-Renewal and Lineage Priming of Hematopoietic Stem Cells and for the Maintenance of Epigenetic Configurations in Multipotent Progenitors
- The SPF27 Homologue Num1 Connects Splicing and Kinesin 1-Dependent Cytoplasmic Trafficking in
- Down-Regulation of eIF4GII by miR-520c-3p Represses Diffuse Large B Cell Lymphoma Development
- Genome Sequencing Highlights the Dynamic Early History of Dogs
- Re-sequencing Expands Our Understanding of the Phenotypic Impact of Variants at GWAS Loci
- Meta-Analysis Identifies Gene-by-Environment Interactions as Demonstrated in a Study of 4,965 Mice
- , a -Antisense Gene of , Encodes a Evolved Protein That Inhibits GSK3β Resulting in the Stabilization of MYCN in Human Neuroblastomas
- A Transcription Factor Is Wound-Induced at the Planarian Midline and Required for Anterior Pole Regeneration
- A Comprehensive tRNA Deletion Library Unravels the Genetic Architecture of the tRNA Pool
- A PNPase Dependent CRISPR System in
- Genomic Confirmation of Hybridisation and Recent Inbreeding in a Vector-Isolated Population
- Zinc Finger Transcription Factors Displaced SREBP Proteins as the Major Sterol Regulators during Saccharomycotina Evolution
- GATA6 Is a Crucial Regulator of Shh in the Limb Bud
- Tissue Specific Roles for the Ribosome Biogenesis Factor Wdr43 in Zebrafish Development
- A Cell Cycle and Nutritional Checkpoint Controlling Bacterial Surface Adhesion
- High Risk Population Isolate Reveals Low Frequency Variants Predisposing to Intracranial Aneurysms
- E3 Ubiquitin Ligase CHIP and NBR1-Mediated Selective Autophagy Protect Additively against Proteotoxicity in Plant Stress Responses
- Evolutionary Rate Covariation Identifies New Members of a Protein Network Required for Female Post-Mating Responses
- 3′ Untranslated Regions Mediate Transcriptional Interference between Convergent Genes Both Locally and Ectopically in
- Single Nucleus Genome Sequencing Reveals High Similarity among Nuclei of an Endomycorrhizal Fungus
- Metabolic QTL Analysis Links Chloroquine Resistance in to Impaired Hemoglobin Catabolism
- Notch Controls Cell Adhesion in the Drosophila Eye
- AL PHD-PRC1 Complexes Promote Seed Germination through H3K4me3-to-H3K27me3 Chromatin State Switch in Repression of Seed Developmental Genes
- Genomes Reveal Evolution of Microalgal Oleaginous Traits
- Large Inverted Duplications in the Human Genome Form via a Fold-Back Mechanism
- Variation in Genome-Wide Levels of Meiotic Recombination Is Established at the Onset of Prophase in Mammalian Males
- Age, Gender, and Cancer but Not Neurodegenerative and Cardiovascular Diseases Strongly Modulate Systemic Effect of the Apolipoprotein E4 Allele on Lifespan
- Lifespan Extension Conferred by Endoplasmic Reticulum Secretory Pathway Deficiency Requires Induction of the Unfolded Protein Response
- Is Non-Homologous End-Joining Really an Inherently Error-Prone Process?
- Vestigialization of an Allosteric Switch: Genetic and Structural Mechanisms for the Evolution of Constitutive Activity in a Steroid Hormone Receptor
- Functional Divergence and Evolutionary Turnover in Mammalian Phosphoproteomes
- A 660-Kb Deletion with Antagonistic Effects on Fertility and Milk Production Segregates at High Frequency in Nordic Red Cattle: Additional Evidence for the Common Occurrence of Balancing Selection in Livestock
- Comparative Evolutionary and Developmental Dynamics of the Cotton () Fiber Transcriptome
- The Transcription Factor BcLTF1 Regulates Virulence and Light Responses in the Necrotrophic Plant Pathogen
- Crossover Patterning by the Beam-Film Model: Analysis and Implications
- Single Cell Genomics: Advances and Future Perspectives
- PLOS Genetics
- Archív čísel
- Aktuálne číslo
- Informácie o časopise
Najčítanejšie v tomto čísle- GATA6 Is a Crucial Regulator of Shh in the Limb Bud
- Large Inverted Duplications in the Human Genome Form via a Fold-Back Mechanism
- Differential Effects of Collagen Prolyl 3-Hydroxylation on Skeletal Tissues
- Affects Plant Architecture by Regulating Local Auxin Biosynthesis
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