-
Články
- Časopisy
- Kurzy
- Témy
- Kongresy
- Videa
- Podcasty
Keeping mtDNA in Shape between Generations
Since the unexpected discovery that mitochondria contain their own distinct DNA molecules, studies of the mitochondrial DNA (mtDNA) have yielded many surprises. In animals, transmission of the mtDNA genome is explicitly non-Mendelian, with a very high number of genome copies being inherited from the mother after a drastic bottleneck. Recent work has begun to uncover the molecular details of this unusual mode of transmission. Many surprising variations in animal mitochondrial biology are known; however, a series of recent studies have identified a core of evolutionarily conserved mechanisms relating to mtDNA inheritance, e.g., mtDNA bottlenecks during germ cell development, selection against specific mtDNA mutation types during maternal transmission, and targeted destruction of sperm mitochondria. In this review, we outline recent literature on the transmission of mtDNA in animals and highlight the implications for human health and ageing.
Vyšlo v časopise: Keeping mtDNA in Shape between Generations. PLoS Genet 10(10): e32767. doi:10.1371/journal.pgen.1004670
Kategorie: Review
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004670Souhrn
Since the unexpected discovery that mitochondria contain their own distinct DNA molecules, studies of the mitochondrial DNA (mtDNA) have yielded many surprises. In animals, transmission of the mtDNA genome is explicitly non-Mendelian, with a very high number of genome copies being inherited from the mother after a drastic bottleneck. Recent work has begun to uncover the molecular details of this unusual mode of transmission. Many surprising variations in animal mitochondrial biology are known; however, a series of recent studies have identified a core of evolutionarily conserved mechanisms relating to mtDNA inheritance, e.g., mtDNA bottlenecks during germ cell development, selection against specific mtDNA mutation types during maternal transmission, and targeted destruction of sperm mitochondria. In this review, we outline recent literature on the transmission of mtDNA in animals and highlight the implications for human health and ageing.
Zdroje
1. RochetteNC, Brochier-ArmanetC, GouyM (2014) Phylogenomic Test of the Hypotheses for the Evolutionary Origin of Eukaryotes. Mol Biol Evol 4 : 832–845.
2. MullerM, MentelM, van HellemondJJ, HenzeK, WoehleC, et al. (2012) Biochemistry and evolution of anaerobic energy metabolism in eukaryotes. Microbiol Mol Biol Rev 76 : 444–495.
3. KarlbergO, CanbackB, KurlandCG, AnderssonSG (2000) The dual origin of the yeast mitochondrial proteome. Yeast 17 : 170–187.
4. PagliariniDJ, CalvoSE, ChangB, ShethSA, VafaiSB, et al. (2008) A mitochondrial protein compendium elucidates complex I disease biology. Cell 134 : 112–123.
5. MeisingerC, SickmannA, PfannerN (2008) The mitochondrial proteome: from inventory to function. Cell 134 : 22–24.
6. BurgerG, GrayMW, Franz LangB (2003) Mitochondrial genomes: anything goes. Trends Genet 19 : 709–716.
7. NassMM, NassS (1963) Intramitochondrial Fibers with DNA Characteristics. I. Fixation and Electron Staining Reactions. J Cell Biol 19 : 593–611.
8. NassS, NassMM (1964) Intramitochondrial Fibers with Deoxyribonucleic Acid Characteristics: Observations of Ehrlich Ascites Tumor Cells. J Natl Cancer Inst 33 : 777–798.
9. NassMM, NassS, AfzeliusBA (1965) The General Occurence of Mitochondrial DNA. Exp Cell Res 37 : 516–539.
10. HikosakaK, KitaK, TanabeK (2013) Diversity of mitochondrial genome structure in the phylum Apicomplexa. Mol Biochem Parasitol 188 : 26–33.
11. SlamovitsCH, SaldarriagaJF, LarocqueA, KeelingPJ (2007) The highly reduced and fragmented mitochondrial genome of the early-branching dinoflagellate Oxyrrhis marina shares characteristics with both apicomplexan and dinoflagellate mitochondrial genomes. J Mol Biol 372 : 356–368.
12. LevinLA (2010) Anaerobic metazoans: no longer an oxymoron. BMC Biol 8 : 31.
13. DanovaroR, Dell'AnnoA, PuscedduA, GambiC, HeinerI, et al. (2010) The first metazoa living in permanently anoxic conditions. BMC Biol 8 : 30.
14. BerntM, BrabandA, SchierwaterB, StadlerPF (2013) Genetic aspects of mitochondrial genome evolution. Mol Phylogenet Evol 69 : 328–338.
15. FalkenbergM, LarssonNG, GustafssonCM (2007) DNA replication and transcription in mammalian mitochondria. Annu Rev Biochem 76 : 679–699.
16. BooreJL (1999) Animal mitochondrial genomes. Nucleic Acids Res 27 : 1767–1780.
17. YangJS, YangWJ (2008) The complete mitochondrial genome sequence of the hydrothermal vent galatheid crab Shinkaia crosnieri (Crustacea: Decapoda: Anomura): a novel arrangement and incomplete tRNA suite. BMC Genomics 9 : 257.
18. DornerM, AltmannM, PääboS, MorlM (2001) Evidence for import of a lysyl-tRNA into marsupial mitochondria. Mol Biol Cell 12 : 2688–2698.
19. MercerTR, NephS, DingerME, CrawfordJ, SmithMA, et al. (2011) The human mitochondrial transcriptome. Cell 146 : 645–658.
20. BeckenbachAT, JoyJB (2009) Evolution of the Mitochondrial Genomes of Gall Midges (Diptera: Cecidomyiidae): Rearrangement and Severe Truncation of tRNA Genes. Genome Biol Evol 1 : 278–287.
21. MastaSE, BooreJL (2008) Parallel evolution of truncated transfer RNA genes in arachnid mitochondrial genomes. Mol Biol Evol 25 : 949–959.
22. MastaSE, BooreJL (2004) The complete mitochondrial genome sequence of the spider Habronattus oregonensis reveals rearranged and extremely truncated tRNAs. Mol Biol Evol 21 : 893–902.
23. SegoviaR, PettW, TrewickS, LavrovDV (2011) Extensive and evolutionarily persistent mitochondrial tRNA editing in Velvet Worms (phylum Onychophora). Mol Biol Evol 28 : 2873–2881.
24. ShaoZ, GrafS, ChagaOY, LavrovDV (2006) Mitochondrial genome of the moon jelly Aurelia aurita (Cnidaria, Scyphozoa): A linear DNA molecule encoding a putative DNA-dependent DNA polymerase. Gene 381 : 92–101.
25. WangX, LavrovDV (2008) Seventeen new complete mtDNA sequences reveal extensive mitochondrial genome evolution within the Demospongiae. PLoS ONE 3: e2723.
26. AmeurA, StewartJB, FreyerC, HagströmE, IngmanM, et al. (2011) Ultra-Deep Sequencing of Mouse Mitochondrial DNA: Mutational Patterns and Their Origins. PLoS Genet 7: e1002028.
27. SeidmanD, JohsnonD, GerbasiV, GoldenD, OrlandoR, et al. (2012) A Mitochondrial membrane complex that contains proteins necessary for tRNA import in Trypanosoma brucei. J Biol Chem 12 : 8892–8903.
28. ChinneryPF, SamuelsDC (1999) Relaxed replication of mtDNA: A model with implications for the expression of disease. Am J Hum Genet 64 : 1158–1165.
29. AshleyMV, LaipisPJ, HauswirthWW (1989) Rapid segregation of heteroplasmic bovine mitochondria. Nucleic Acids Res 17 : 7325–7331.
30. OlivoPD, Van de WalleMJ, LaipisPJ, HauswirthWW (1983) Nucleotide sequence evidence for rapid genotypic shifts in the bovine mitochondrial DNA D-loop. Nature 306 : 400–402.
31. HauswirthWW, LaipisPJ (1982) Mitochondrial DNA polymorphism in a maternal lineage of Holstein cows. Proc Natl Acad Sci U S A 79 : 4686–4690.
32. JenuthJP, PetersonAC, FuK, ShoubridgeEA (1996) Random genetic drift in the female germline explains the rapid segregation of mammalian mitochondrial DNA. Nat Genet 14 : 146–151.
33. WolffJN, WhiteDJ, WoodhamsM, WhiteHE, GemmellNJ (2011) The strength and timing of the mitochondrial bottleneck in salmon suggests a conserved mechanism in vertebrates. PLoS ONE 6: e20522.
34. CreeLM, SamuelsDC, de Sousa LopesSC, RajasimhaHK, WonnapinijP, et al. (2008) A reduction of mitochondrial DNA molecules during embryogenesis explains the rapid segregation of genotypes. Nat Genet 40 : 249–254.
35. zPetitN, TourailleS, DebiseR, MorelF, RenouxM, et al. (1998) Developmental changes in heteroplasmy level and mitochondrial gene expression in a Drosophila subobscura mitochondrial deletion mutant. Curr Genet 33 : 330–339.
36. MaH, XuH, O'FarrellPH (2014) Transmission of mitochondrial mutations and action of purifying selection in Drosophila melanogaster. Nat Genet 46 : 393–397.
37. HillJH, ChenZ, XuH (2014) Selective propagation of functional mitochondrial DNA during oogenesis restricts the transmission of a deleterious mitochondrial variant. Nat Genet 46 : 389–392.
38. ShitaraH, KanedaH, SatoA, InoueK, OguraA, et al. (2000) Selective and continuous elimination of mitochondria microinjected into mouse eggs from spermatids, but not from liver cells, occurs throughout embryogenesis. Genetics 156 : 1277–1284.
39. DeLucaSZ, O'FarrellPH (2012) Barriers to male transmission of mitochondrial DNA in sperm development. Dev Cell 22 : 660–668.
40. SatoM, SatoK (2011) Degradation of paternal mitochondria by fertilization-triggered autophagy in C. elegans embryos. Science 334 : 1141–1144.
41. Al RawiS, Louvet-ValleeS, DjeddiA, SachseM, CulettoE, et al. (2011) Postfertilization autophagy of sperm organelles prevents paternal mitochondrial DNA transmission. Science 334 : 1144–1147.
42. StewartDT, SaavedraC, StanwoodRR, BallAO, ZourosE (1995) Male and female mitochondrial DNA lineages in the blue mussel (Mytilus edulis) species group. Mol Biol Evol 12 : 735–747.
43. GyllenstenU, WhartonD, JosefssonA, WilsonAC (1991) Paternal inheritance of mitochondrial DNA in mice. Nature 352 : 255–257.
44. GyllenstenU, WhartonD, WilsonAC (1985) Maternal inheritance of mitochondrial DNA during backcrossing of two species of mice. J Hered 76 : 321–324.
45. UjvariB, DowtonM, MadsenT (2007) Mitochondrial DNA recombination in a free-ranging Australian lizard. Biol Lett 3 : 189–192.
46. GuoX, LiuS, LiuY (2006) Evidence for recombination of mitochondrial DNA in triploid crucian carp. Genetics 172 : 1745–1749.
47. LadoukakisED, TheologidisI, RodakisGC, ZourosE (2011) Homologous recombination between highly diverged mitochondrial sequences: examples from maternally and paternally transmitted genomes. Mol Biol Evol 28 : 1847–1859.
48. SatoA, NakadaK, AkimotoM, IshikawaK, OnoT, et al. (2005) Rare creation of recombinant mtDNA haplotypes in mammalian tissues. Proc Natl Acad Sci U S A 102 : 6057–6062.
49. HagstromE, FreyerC, BattersbyBJ, StewartJB, LarssonNG (2014) No recombination of mtDNA after heteroplasmy for 50 generations in the mouse maternal germline. Nucleic Acids Res 42 : 1111–1116.
50. PesceM, ScholerHR (2001) Oct-4: gatekeeper in the beginnings of mammalian development. Stem Cells 19 : 271–278.
51. PikoL, TaylorKD (1987) Amounts of mitochondrial DNA and abundance of some mitochondrial gene transcripts in early mouse embryos. Dev Biol 123 : 364–374.
52. WaiT, AoA, ZhangX, CyrD, DufortD, et al. (2010) The role of mitochondrial DNA copy number in mammalian fertility. Biol Reprod 83 : 52–62.
53. CaoL, ShitaraH, HoriiT, NagaoY, ImaiH, et al. (2007) The mitochondrial bottleneck occurs without reduction of mtDNA content in female mouse germ cells. Nat Genet 39 : 386–390.
54. WaiT, TeoliD, ShoubridgeEA (2008) The mitochondrial DNA genetic bottleneck results from replication of a subpopulation of genomes. Nat Genet 40 : 1484–1488.
55. CaoL, ShitaraH, SugimotoM, HayashiJ, AbeK, et al. (2009) New evidence confirms that the mitochondrial bottleneck is generated without reduction of mitochondrial DNA content in early primordial germ cells of mice. PLoS Genet 5: e1000756.
56. WaiT, ShoubridgeEA (2010) Reply to “Reassessing evidence for a postnatal mitochondrial genetic bottleneck”. Nat Genet 42 : 472–473.
57. SamuelsDC, WonnapinijP, CreeLM, ChinneryPF (2010) Reassessing evidence for a postnatal mitochondrial genetic bottleneck. Nat Genet 42 : 471–472 author reply 472–473.
58. Haag-LiautardC, CoffeyN, HouleD, LynchM, CharlesworthB, et al. (2008) Direct Estimation of the Mitochondrial DNA Mutation Rate in Drosophila melanogaster. PLoS Biol 6: e204.
59. PikoL, HoughamAJ, BulpittKJ (1988) Studies of sequence heterogeneity of mitochondrial DNA from rat and mouse tissues: evidence for an increased frequency of deletions/additions with aging. Mech Ageing Dev 43 : 279–293.
60. KatayamaM, TanakaM, YamamotoH, OhbayashiT, NimuraY, et al. (1991) Deleted mitochondrial DNA in the skeletal muscle of aged individuals. Biochem Int 25 : 47–56.
61. WilliamsSL, HuangJ, EdwardsYJ, UlloaRH, DillonLM, et al. (2010) The mtDNA mutation spectrum of the progeroid Polg mutator mouse includes abundant control region multimers. Cell Metab 12 : 675–682.
62. WilliamsSL, MashDC, ZuchnerS, MoraesCT (2013) Somatic mtDNA mutation spectra in the aging human putamen. PLoS Genet 9: e1003990.
63. TrifunovicA, WredenbergA, FalkenbergM, SpelbrinkJN, RovioAT, et al. (2004) Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 429 : 417–423.
64. KornblumC, NichollsTJ, HaackTB, ScholerS, PeevaV, et al. (2013) Loss-of-function mutations in MGME1 impair mtDNA replication and cause multisystemic mitochondrial disease. Nat Genet 45 : 214–219.
65. PayneBA, WilsonIJ, Yu-Wai-ManP, CoxheadJ, DeehanD, et al. (2013) Universal heteroplasmy of human mitochondrial DNA. Hum Mol Genet 22 : 384–390.
66. LiM, SchonbergA, SchaeferM, SchroederR, NasidzeI, et al. (2010) Detecting heteroplasmy from high-throughput sequencing of complete human mitochondrial DNA genomes. Am J Hum Genet 87 : 237–249.
67. HeY, WuJ, DressmanDC, Iacobuzio-DonahueC, MarkowitzSD, et al. (2010) Heteroplasmic mitochondrial DNA mutations in normal and tumour cells. Nature 464 : 610–614.
68. LarssonNG (2010) Somatic mitochondrial DNA mutations in mammalian aging. Annu Rev Biochem 79 : 683–706.
69. HarmanD (1972) The biologic clock: the mitochondria? J Am Geriatr Soc 20 : 145–147.
70. HarmanD (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11 : 298–300.
71. ZhengW, KhrapkoK, CollerHA, ThillyWG, CopelandWC (2006) Origins of human mitochondrial point mutations as DNA polymerase gamma-mediated errors. Mutat Res 599 : 11–20.
72. KhrapkoK, CollerHA, AndrePC, LiXC, HanekampJS, et al. (1997) Mitochondrial mutational spectra in human cells and tissues. Proc Natl Acad Sci U S A 94 : 13798–13803.
73. ItsaraLS, KennedySR, FoxEJ, YuS, HewittJJ, et al. (2014) Oxidative stress is not a major contributor to somatic mitochondrial DNA mutations. PLoS Genet 10: e1003974.
74. KennedySR, SalkJJ, SchmittMW, LoebLA (2013) Ultra-sensitive sequencing reveals an age-related increase in somatic mitochondrial mutations that are inconsistent with oxidative damage. PLoS Genet 9: e1003794.
75. FayetG, JanssonM, SternbergD, MoslemiAR, BlondyP, et al. (2002) Ageing muscle: clonal expansions of mitochondrial DNA point mutations and deletions cause focal impairment of mitochondrial function. Neuromuscul Disord 12 : 484–493.
76. CottrellDA, IncePG, WardellTM, TurnbullDM, JohnsonMA (2001) Accelerated ageing changes in the choroid plexus of a case with multiple mitochondrial DNA deletions. Neuropathol Appl Neurobiol 27 : 206–214.
77. TaylorRW, BarronMJ, BorthwickGM, GospelA, ChinneryPF, et al. (2003) Mitochondrial DNA mutations in human colonic crypt stem cells. J Clin Invest 112 : 1351–1360.
78. GreavesLC, ElsonJL, NooteboomM, GradyJP, TaylorGA, et al. (2012) Comparison of mitochondrial mutation spectra in ageing human colonic epithelium and disease: absence of evidence for purifying selection in somatic mitochondrial DNA point mutations. PLoS Genet 8: e1003082.
79. PereiraL, SoaresP, MaximoV, SamuelsDC (2012) Somatic mitochondrial DNA mutations in cancer escape purifying selection and high pathogenicity mutations lead to the oncocytic phenotype: pathogenicity analysis of reported somatic mtDNA mutations in tumors. BMC Cancer 12 : 53.
80. TrifunovicA, HanssonA, WredenbergA, RovioAT, DufourE, et al. (2005) Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production. Proc Natl Acad Sci U S A 102 : 17993–17998.
81. KujothGC, HionaA, PughTD, SomeyaS, PanzerK, et al. (2005) Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science 309 : 481–484.
82. SamuelsDC, LiC, LiB, SongZ, TorstensonE, et al. (2013) Recurrent tissue-specific mtDNA mutations are common in humans. PLoS Genet 9: e1003929.
83. RandDM (2011) Population genetics of the cytoplasm and the units of selection on mitochondrial DNA in Drosophila melanogaster. Genetica 139 : 685–697.
84. LiauWS, Gonzalez-SerricchioAS, DeshommesC, ChinK, LaMunyonCW (2007) A persistent mitochondrial deletion reduces fitness and sperm performance in heteroplasmic populations of C. elegans. BMC Genet 8 : 8.
85. WanrooijS, Miralles FusteJ, StewartJB, WanrooijPH, SamuelssonT, et al. (2012) In vivo mutagenesis reveals that OriL is essential for mitochondrial DNA replication. EMBO Rep 13 : 1130–1137.
86. RossJM, StewartJB, HagstromE, BreneS, MourierA, et al. (2013) Germline mitochondrial DNA mutations aggravate ageing and can impair brain development. Nature 501 : 412–415.
87. LynchM (1996) Mutation accumulation in transfer RNAs: molecular evidence for Muller's ratchet in mitochondrial genomes. Mol Biol Evol 13 : 209–220.
88. TaylorRW, TurnbullDM (2005) Mitochondrial DNA mutations in human disease. Nat Rev Genet 6 : 389–402.
89. LarssonNG, TuliniusMH, HolmeE, OldforsA, AndersenO, et al. (1992) Segregation and manifestations of the mtDNA tRNA(Lys) A→G(8344) mutation of myoclonus epilepsy and ragged-red fibers (MERRF) syndrome. Am J Hum Genet 51 : 1201–1212.
90. MullerHJ (1964) The Relation of Recombination to Mutational Advance. Mutat Res 1 : 2–9.
91. FelsensteinJ (1974) The evolutionary advantage of recombination. Genetics 78 : 737–756.
92. StewartJB, FreyerC, ElsonJL, WredenbergA, CansuZ, et al. (2008) Strong Purifying Selection in Transmission of Mammalian Mitochondrial DNA. PLoS Biol 6: e10.
93. FanW, WaymireKG, NarulaN, LiP, RocherC, et al. (2008) A Mouse Model of Mitochondrial Disease Reveals Germline Selection Against Severe mtDNA Mutations. Science 319 : 958–962.
94. FreyerC, CreeLM, MourierA, StewartJB, KoolmeisterC, et al. (2012) Variation in germline mtDNA heteroplasmy is determined prenatally but modified during subsequent transmission. Nat Genet 44 : 1282–1285.
Štítky
Genetika Reprodukčná medicína
Článek Oligoasthenoteratozoospermia and Infertility in Mice Deficient for miR-34b/c and miR-449 LociČlánek The Kinesin AtPSS1 Promotes Synapsis and is Required for Proper Crossover Distribution in MeiosisČlánek Payoffs, Not Tradeoffs, in the Adaptation of a Virus to Ostensibly Conflicting Selective PressuresČlánek Examination of Prokaryotic Multipartite Genome Evolution through Experimental Genome ReductionČlánek BMP-FGF Signaling Axis Mediates Wnt-Induced Epidermal Stratification in Developing Mammalian SkinČlánek Role of STN1 and DNA Polymerase α in Telomere Stability and Genome-Wide Replication in ArabidopsisČlánek RNA-Processing Protein TDP-43 Regulates FOXO-Dependent Protein Quality Control in Stress ResponseČlánek Integrating Functional Data to Prioritize Causal Variants in Statistical Fine-Mapping StudiesČlánek Salt-Induced Stabilization of EIN3/EIL1 Confers Salinity Tolerance by Deterring ROS Accumulation inČlánek Ethylene-Induced Inhibition of Root Growth Requires Abscisic Acid Function in Rice ( L.) SeedlingsČlánek Metabolic Respiration Induces AMPK- and Ire1p-Dependent Activation of the p38-Type HOG MAPK PathwayČlánek Signature Gene Expression Reveals Novel Clues to the Molecular Mechanisms of Dimorphic Transition inČlánek A Mouse Model Uncovers LKB1 as an UVB-Induced DNA Damage Sensor Mediating CDKN1A (p21) DegradationČlánek Dominant Sequences of Human Major Histocompatibility Complex Conserved Extended Haplotypes from to
Článok vyšiel v časopisePLOS Genetics
Najčítanejšie tento týždeň
2014 Číslo 10- 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
- An Deletion Is Highly Associated with a Juvenile-Onset Inherited Polyneuropathy in Leonberger and Saint Bernard Dogs
- Licensing of Yeast Centrosome Duplication Requires Phosphoregulation of Sfi1
- Oligoasthenoteratozoospermia and Infertility in Mice Deficient for miR-34b/c and miR-449 Loci
- Basement Membrane and Cell Integrity of Self-Tissues in Maintaining Immunological Tolerance
- The Kinesin AtPSS1 Promotes Synapsis and is Required for Proper Crossover Distribution in Meiosis
- Germline Mutations in Are Associated with Familial Gastric Cancer
- POT1a and Components of CST Engage Telomerase and Regulate Its Activity in
- Controlling Meiotic Recombinational Repair – Specifying the Roles of ZMMs, Sgs1 and Mus81/Mms4 in Crossover Formation
- Payoffs, Not Tradeoffs, in the Adaptation of a Virus to Ostensibly Conflicting Selective Pressures
- FHIT Suppresses Epithelial-Mesenchymal Transition (EMT) and Metastasis in Lung Cancer through Modulation of MicroRNAs
- Genome-Wide Mapping of Yeast RNA Polymerase II Termination
- Examination of Prokaryotic Multipartite Genome Evolution through Experimental Genome Reduction
- White Cells Facilitate Opposite- and Same-Sex Mating of Opaque Cells in
- BMP-FGF Signaling Axis Mediates Wnt-Induced Epidermal Stratification in Developing Mammalian Skin
- Genome-Wide Association Study of CSF Levels of 59 Alzheimer's Disease Candidate Proteins: Significant Associations with Proteins Involved in Amyloid Processing and Inflammation
- COE Loss-of-Function Analysis Reveals a Genetic Program Underlying Maintenance and Regeneration of the Nervous System in Planarians
- Fat-Dachsous Signaling Coordinates Cartilage Differentiation and Polarity during Craniofacial Development
- Identification of Genes Important for Cutaneous Function Revealed by a Large Scale Reverse Genetic Screen in the Mouse
- Sensors at Centrosomes Reveal Determinants of Local Separase Activity
- Genes Integrate and Hedgehog Pathways in the Second Heart Field for Cardiac Septation
- Systematic Dissection of Coding Exons at Single Nucleotide Resolution Supports an Additional Role in Cell-Specific Transcriptional Regulation
- Recovery from an Acute Infection in Requires the GATA Transcription Factor ELT-2
- HIPPO Pathway Members Restrict SOX2 to the Inner Cell Mass Where It Promotes ICM Fates in the Mouse Blastocyst
- Role of and in Development of Abdominal Epithelia Breaks Posterior Prevalence Rule
- The Formation of Endoderm-Derived Taste Sensory Organs Requires a -Dependent Expansion of Embryonic Taste Bud Progenitor Cells
- Role of STN1 and DNA Polymerase α in Telomere Stability and Genome-Wide Replication in Arabidopsis
- Keratin 76 Is Required for Tight Junction Function and Maintenance of the Skin Barrier
- Encodes the Catalytic Subunit of N Alpha-Acetyltransferase that Regulates Development, Metabolism and Adult Lifespan
- Disruption of SUMO-Specific Protease 2 Induces Mitochondria Mediated Neurodegeneration
- Caudal Regulates the Spatiotemporal Dynamics of Pair-Rule Waves in
- It's All in Your Mind: Determining Germ Cell Fate by Neuronal IRE-1 in
- A Conserved Role for Homologs in Protecting Dopaminergic Neurons from Oxidative Stress
- The Master Activator of IncA/C Conjugative Plasmids Stimulates Genomic Islands and Multidrug Resistance Dissemination
- An AGEF-1/Arf GTPase/AP-1 Ensemble Antagonizes LET-23 EGFR Basolateral Localization and Signaling during Vulva Induction
- The Proteomic Landscape of the Suprachiasmatic Nucleus Clock Reveals Large-Scale Coordination of Key Biological Processes
- RNA-Processing Protein TDP-43 Regulates FOXO-Dependent Protein Quality Control in Stress Response
- A Complex Genetic Switch Involving Overlapping Divergent Promoters and DNA Looping Regulates Expression of Conjugation Genes of a Gram-positive Plasmid
- ZTF-8 Interacts with the 9-1-1 Complex and Is Required for DNA Damage Response and Double-Strand Break Repair in the Germline
- Integrating Functional Data to Prioritize Causal Variants in Statistical Fine-Mapping Studies
- Tpz1-Ccq1 and Tpz1-Poz1 Interactions within Fission Yeast Shelterin Modulate Ccq1 Thr93 Phosphorylation and Telomerase Recruitment
- Salt-Induced Stabilization of EIN3/EIL1 Confers Salinity Tolerance by Deterring ROS Accumulation in
- Telomeric (s) in spp. Encode Mediator Subunits That Regulate Distinct Virulence Traits
- Ethylene-Induced Inhibition of Root Growth Requires Abscisic Acid Function in Rice ( L.) Seedlings
- Ancient Expansion of the Hox Cluster in Lepidoptera Generated Four Homeobox Genes Implicated in Extra-Embryonic Tissue Formation
- Mechanism of Suppression of Chromosomal Instability by DNA Polymerase POLQ
- A Mutation in the Mouse Gene Leads to Impaired Hedgehog Signaling
- Keeping mtDNA in Shape between Generations
- Targeted Exon Capture and Sequencing in Sporadic Amyotrophic Lateral Sclerosis
- TIF-IA-Dependent Regulation of Ribosome Synthesis in Muscle Is Required to Maintain Systemic Insulin Signaling and Larval Growth
- At Short Telomeres Tel1 Directs Early Replication and Phosphorylates Rif1
- Evidence of a Bacterial Receptor for Lysozyme: Binding of Lysozyme to the Anti-σ Factor RsiV Controls Activation of the ECF σ Factor σ
- Hsp40s Specify Functions of Hsp104 and Hsp90 Protein Chaperone Machines
- Feeding State, Insulin and NPR-1 Modulate Chemoreceptor Gene Expression via Integration of Sensory and Circuit Inputs
- Functional Interaction between Ribosomal Protein L6 and RbgA during Ribosome Assembly
- Multiple Regulatory Systems Coordinate DNA Replication with Cell Growth in
- Fast Evolution from Precast Bricks: Genomics of Young Freshwater Populations of Threespine Stickleback
- Mmp1 Processing of the PDF Neuropeptide Regulates Circadian Structural Plasticity of Pacemaker Neurons
- The Nuclear Immune Receptor Is Required for -Dependent Constitutive Defense Activation in
- Genetic Modifiers of Neurofibromatosis Type 1-Associated Café-au-Lait Macule Count Identified Using Multi-platform Analysis
- Juvenile Hormone-Receptor Complex Acts on and to Promote Polyploidy and Vitellogenesis in the Migratory Locust
- Uncovering Enhancer Functions Using the α-Globin Locus
- The Analysis of Mutant Alleles of Different Strength Reveals Multiple Functions of Topoisomerase 2 in Regulation of Chromosome Structure
- Metabolic Respiration Induces AMPK- and Ire1p-Dependent Activation of the p38-Type HOG MAPK Pathway
- The Specification and Global Reprogramming of Histone Epigenetic Marks during Gamete Formation and Early Embryo Development in
- The DAF-16 FOXO Transcription Factor Regulates to Modulate Stress Resistance in , Linking Insulin/IGF-1 Signaling to Protein N-Terminal Acetylation
- Genetic Influences on Translation in Yeast
- Analysis of Mutants Defective in the Cdk8 Module of Mediator Reveal Links between Metabolism and Biofilm Formation
- Ribosomal Readthrough at a Short UGA Stop Codon Context Triggers Dual Localization of Metabolic Enzymes in Fungi and Animals
- Gene Duplication Restores the Viability of Δ and Δ Mutants
- Selection on a Variant Associated with Improved Viral Clearance Drives Local, Adaptive Pseudogenization of Interferon Lambda 4 ()
- Break-Induced Replication Requires DNA Damage-Induced Phosphorylation of Pif1 and Leads to Telomere Lengthening
- Dynamic Partnership between TFIIH, PGC-1α and SIRT1 Is Impaired in Trichothiodystrophy
- Signature Gene Expression Reveals Novel Clues to the Molecular Mechanisms of Dimorphic Transition in
- Mutations in Moderate or Severe Intellectual Disability
- Multifaceted Genome Control by Set1 Dependent and Independent of H3K4 Methylation and the Set1C/COMPASS Complex
- A Role for Taiman in Insect Metamorphosis
- The Small RNA Rli27 Regulates a Cell Wall Protein inside Eukaryotic Cells by Targeting a Long 5′-UTR Variant
- MMS Exposure Promotes Increased MtDNA Mutagenesis in the Presence of Replication-Defective Disease-Associated DNA Polymerase γ Variants
- Coexistence and Within-Host Evolution of Diversified Lineages of Hypermutable in Long-term Cystic Fibrosis Infections
- Comprehensive Mapping of the Flagellar Regulatory Network
- Topoisomerase II Is Required for the Proper Separation of Heterochromatic Regions during Female Meiosis
- A Splice Mutation in the Gene Causes High Glycogen Content and Low Meat Quality in Pig Skeletal Muscle
- KDM5 Interacts with Foxo to Modulate Cellular Levels of Oxidative Stress
- H2B Mono-ubiquitylation Facilitates Fork Stalling and Recovery during Replication Stress by Coordinating Rad53 Activation and Chromatin Assembly
- Copy Number Variation in the Horse Genome
- Unifying Genetic Canalization, Genetic Constraint, and Genotype-by-Environment Interaction: QTL by Genomic Background by Environment Interaction of Flowering Time in
- Spinster Homolog 2 () Deficiency Causes Early Onset Progressive Hearing Loss
- Genome-Wide Discovery of Drug-Dependent Human Liver Regulatory Elements
- Developmentally-Regulated Excision of the SPβ Prophage Reconstitutes a Gene Required for Spore Envelope Maturation in
- Protein Phosphatase 4 Promotes Chromosome Pairing and Synapsis, and Contributes to Maintaining Crossover Competence with Increasing Age
- The bHLH-PAS Transcription Factor Dysfusion Regulates Tarsal Joint Formation in Response to Notch Activity during Leg Development
- A Mouse Model Uncovers LKB1 as an UVB-Induced DNA Damage Sensor Mediating CDKN1A (p21) Degradation
- Notch3 Interactome Analysis Identified WWP2 as a Negative Regulator of Notch3 Signaling in Ovarian Cancer
- An Integrated Cell Purification and Genomics Strategy Reveals Multiple Regulators of Pancreas Development
- Dominant Sequences of Human Major Histocompatibility Complex Conserved Extended Haplotypes from to
- The Vesicle Protein SAM-4 Regulates the Processivity of Synaptic Vesicle Transport
- A Gain-of-Function Mutation in Impeded Bone Development through Increasing Expression in DA2B Mice
- Nephronophthisis-Associated Regulates Cell Cycle Progression, Apoptosis and Epithelial-to-Mesenchymal Transition
- Beclin 1 Is Required for Neuron Viability and Regulates Endosome Pathways via the UVRAG-VPS34 Complex
- The Not5 Subunit of the Ccr4-Not Complex Connects Transcription and Translation
- Abnormal Dosage of Ultraconserved Elements Is Highly Disfavored in Healthy Cells but Not Cancer Cells
- Genome-Wide Distribution of RNA-DNA Hybrids Identifies RNase H Targets in tRNA Genes, Retrotransposons and Mitochondria
- The Chromosomal Association of the Smc5/6 Complex Depends on Cohesion and Predicts the Level of Sister Chromatid Entanglement
- Cell-Autonomous Progeroid Changes in Conditional Mouse Models for Repair Endonuclease XPG Deficiency
- PLOS Genetics
- Archív čísel
- Aktuálne číslo
- Informácie o časopise
Najčítanejšie v tomto čísle- The Master Activator of IncA/C Conjugative Plasmids Stimulates Genomic Islands and Multidrug Resistance Dissemination
- A Splice Mutation in the Gene Causes High Glycogen Content and Low Meat Quality in Pig Skeletal Muscle
- Keratin 76 Is Required for Tight Junction Function and Maintenance of the Skin Barrier
- A Role for Taiman in Insect Metamorphosis
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