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An Incompatibility between a Mitochondrial tRNA and Its Nuclear-Encoded tRNA Synthetase Compromises Development and Fitness in


Mitochondrial transcription, translation, and respiration require interactions between genes encoded in two distinct genomes, generating the potential for mutations in nuclear and mitochondrial genomes to interact epistatically and cause incompatibilities that decrease fitness. Mitochondrial-nuclear epistasis for fitness has been documented within and between populations and species of diverse taxa, but rarely has the genetic or mechanistic basis of these mitochondrial–nuclear interactions been elucidated, limiting our understanding of which genes harbor variants causing mitochondrial–nuclear disruption and of the pathways and processes that are impacted by mitochondrial–nuclear coevolution. Here we identify an amino acid polymorphism in the Drosophila melanogaster nuclear-encoded mitochondrial tyrosyl–tRNA synthetase that interacts epistatically with a polymorphism in the D. simulans mitochondrial-encoded tRNATyr to significantly delay development, compromise bristle formation, and decrease fecundity. The incompatible genotype specifically decreases the activities of oxidative phosphorylation complexes I, III, and IV that contain mitochondrial-encoded subunits. Combined with the identity of the interacting alleles, this pattern indicates that mitochondrial protein translation is affected by this interaction. Our findings suggest that interactions between mitochondrial tRNAs and their nuclear-encoded tRNA synthetases may be targets of compensatory molecular evolution. Human mitochondrial diseases are often genetically complex and variable in penetrance, and the mitochondrial–nuclear interaction we document provides a plausible mechanism to explain this complexity.


Vyšlo v časopise: An Incompatibility between a Mitochondrial tRNA and Its Nuclear-Encoded tRNA Synthetase Compromises Development and Fitness in. PLoS Genet 9(1): e32767. doi:10.1371/journal.pgen.1003238
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003238

Souhrn

Mitochondrial transcription, translation, and respiration require interactions between genes encoded in two distinct genomes, generating the potential for mutations in nuclear and mitochondrial genomes to interact epistatically and cause incompatibilities that decrease fitness. Mitochondrial-nuclear epistasis for fitness has been documented within and between populations and species of diverse taxa, but rarely has the genetic or mechanistic basis of these mitochondrial–nuclear interactions been elucidated, limiting our understanding of which genes harbor variants causing mitochondrial–nuclear disruption and of the pathways and processes that are impacted by mitochondrial–nuclear coevolution. Here we identify an amino acid polymorphism in the Drosophila melanogaster nuclear-encoded mitochondrial tyrosyl–tRNA synthetase that interacts epistatically with a polymorphism in the D. simulans mitochondrial-encoded tRNATyr to significantly delay development, compromise bristle formation, and decrease fecundity. The incompatible genotype specifically decreases the activities of oxidative phosphorylation complexes I, III, and IV that contain mitochondrial-encoded subunits. Combined with the identity of the interacting alleles, this pattern indicates that mitochondrial protein translation is affected by this interaction. Our findings suggest that interactions between mitochondrial tRNAs and their nuclear-encoded tRNA synthetases may be targets of compensatory molecular evolution. Human mitochondrial diseases are often genetically complex and variable in penetrance, and the mitochondrial–nuclear interaction we document provides a plausible mechanism to explain this complexity.


Zdroje

1. ClarkAG (1985) Natural selection with nuclear and cytoplasmic transmission. II. Tests with Drosophila from diverse populations. Genetics 111: 97–112.

2. ClarkAG, LyckegaardEM (1988) Natural selection with nuclear and cytoplasmic transmission. III. Joint analysis of segregation and mtDNA in Drosophila melanogaster. Genetics 118: 471–481.

3. RandDM, ClarkAG, KannLM (2001) Sexually antagonistic cytonuclear fitness interactions in Drosophila melanogaster. Genetics 159: 173–187.

4. DowlingDK, FribergU, HailerF, ArnqvistG (2007) Intergenomic epistasis for fitness: within-population interactions between cytoplasmic and nuclear genes in Drosophila melanogaster. Genetics 175: 235–244.

5. DowlingDK, AbiegaKC, ArnqvistG (2007) Temperature-specific outcomes of cytoplasmic-nuclear interactions on egg-to-adult development time in seed beetles. Evolution 61: 194–201.

6. BurtonRS, BarretoFS (2012) A disproportionate role for mtDNA in Dobzhansky-Muller incompatibilities? Mol Ecol 21: 4942–4957.

7. RandDM, HaneyRA, FryAJ (2004) Cytonuclear cooperation: the genomics of cooperation. Trends Ecol Evol 19: 645–653.

8. DowlingDK, FribergU, LindellJ (2008) Evolutionary implications of non-neutral mitochondrial genetic variation. Trends Ecol Evol 23: 546–554.

9. OsadaN, AkashiH (2012) Mitochondrial-nuclear interactions and accelerated compensatory evolution: evidence from the primate cytochrome c oxidase complex. Mol Biol Evol 29: 337–346.

10. BlierPU, DufresneF, BurtonRS (2001) Natural selection and the evolution of mtDNA-encoded peptides: evidence for intergenomic co-adaptation. Trends Genet 17: 400–406.

11. BurtonRS, EllisonCK, HarrisonJS (2006) The sorry state of F2 hybrids: consequences of rapid mitochondrial DNA evolution in allopatric populations. Am Nat 168 Suppl 6: S14–24.

12. SacktonTB, HaneyRA, RandDM (2003) Cytonuclear coadaptation in Drosophila: disruption of cytochrome c oxidase activity in backcross genotypes. Evolution 2315–2325.

13. EllisonCK, BurtonRS (2008) Interpopulation hybrid breakdown maps to the mitochondrial genome. Evolution 62: 631–638.

14. LeeH, ChouJ, CheongL, ChangN, YangS, et al. (2008) Incompatibility of nuclear and mitochondrial genomes causes hybrid sterility between two yeast species. Cell 135: 1065–1073.

15. ChouJ, HungYS, LinKH, LeeH, LeuJ (2010) Multiple molecular mechanisms cause reproductive isolation between three yeast species. PLoS Biol 8: e1000432 doi:10.1371/journal.pbio.1000432.

16. MontoothKL, MeiklejohnCD, AbtDN, RandDM (2010) Mitochondrial-nuclear epistasis affects fitness within species but does not contribute to fixed incompatibilities between species of Drosophila. Evolution 3364–3379.

17. McKenzieM, ChiotisM, PinkertCA, TrounceIA (2003) Functional respiratory chain analyses in murid xenomitochondrial cybrids expose coevolutionary constraints of cytochrome b and nuclear subunits of complex III. Mol Biol Evol 20: 1117–1124.

18. RawsonPD, BurtonRS (2002) Functional coadaptation between cytochrome c and cytochrome c oxidase within allopatric populations of a marine copepod. Proc Natl Acad Sci U S A 99: 12955–12958.

19. RawsonPD, BurtonRS (2006) Molecular evolution at the cytochrome oxidase subunit 2 gene among divergent populations of the intertidal copepod, Tigriopus californicus. J Mol Evol 62: 753–764.

20. GoldbergA, WildmanDE, SchmidtTR, HuttemannM, GoodmanM, et al. (2003) Adaptive evolution of cytochrome c oxidase subunit VIII in anthropoid primates. Proc Natl Acad Sci USA 100: 5873–5878.

21. GrossmanLI, WildmanDE, SchmidtTR, GoodmanM (2004) Accelerated evolution of the electron transport chain in anthropoid primates. Trends Genet 20: 578–585.

22. LynchM (1996) Mutation accumulation in transfer RNAs: molecular evidence for Muller's ratchet in mitochondrial genomes. Mol Biol Evol 13: 209–220.

23. LynchM (1997) Mutation accumulation in nuclear, organelle, and prokaryotic transfer RNA genes. Mol Biol Evol 14: 914–925.

24. NeimanM, TaylorDR (2009) The causes of mutation accumulation in mitochondrial genomes. Proc Biol Sci 276: 1201–1209.

25. EllisonCK, BurtonRS (2006) Disruption of mitochondrial function in interpopulation hybrids of Tigriopus californicus. Evolution 1382–1391.

26. EllisonCK, BurtonRS (2008) Genotype-dependent variation of mitochondrial transcriptional profiles in interpopulation hybrids. Proc Natl Acad Sci USA 105: 15831–15836.

27. JacobsHT (2003) Disorders of mitochondrial protein synthesis. Hum Mol Genet 12 Spec No 2: R293–301.

28. Moreno-LoshuertosR, FerrínG, Acín-PérezR, GallardoM, ViscomiC, et al. (2011) Evolution meets disease: penetrance and functional epistasis of mitochondrial tRNA mutations. PLoS Genet 7: e1001379 doi:10.1371/journal.pgen.1001379.

29. SuzukiT, NagaoA, SuzukiT (2011) Human mitochondrial tRNAs: biogenesis, function, structural aspects, and diseases. Annu Rev Genet 45: 299–329.

30. BayatV, ThiffaultI, JaiswalM, TétreaultM, DontiT, et al. (2012) Mutations in the mitochondrial methionyl-tRNA synthetase cause a neurodegenerative phenotype in flies and a recessive ataxia (ARSAL) in humans. PLoS Biol 10: e1001288 doi:10.1371/journal.pbio.1001288.

31. CarelliV, GiordanoC, d'AmatiG (2003) Pathogenic expression of homoplasmic mtDNA mutations needs a complex nuclear-mitochondrial interaction. Trends Genet 19: 257–262.

32. JohnsonKR, ZhengQY, BykhovskayaY, SpirinaO, Fischel-GhodsianN (2001) A nuclear-mitochondrial DNA interaction affecting hearing impairment in mice. Nat Genet 27: 191–194.

33. GuanMX, YanQ, LiX, BykhovskayaY, Gallo-TeranJ, et al. (2006) Mutation in TRMU related to transfer RNA modification modulates the phenotypic expression of the deafness-associated mitochondrial 12S ribosomal RNA mutations. Am J Hum Genet 79: 291–302.

34. BallardJW (2000) Comparative genomics of mitochondrial DNA in members of the Drosophila melanogaster subgroup. J Mol Evol 51: 48–63.

35. MontoothKL, AbtDN, HofmannJ, RandDM (2009) Comparative genomics of Drosophila mtDNA: Novel features of conservation and change across functional domains and lineages. J Mol Evol 69: 94–114.

36. MackayT, RichardsS, StoneE, BarbadillaA, AyrolesJ, et al. (2012) The Drosophila melanogaster genetic reference panel. Nature 482: 173–178.

37. LangleyCH, StevensK, CardenoC, LeeYC, SchriderDR, et al. (2012) Genomic variation in natural populations of Drosophila melanogaster. Genetics 192: 533–598.

38. BonnefondL, FrugierM, TouzéE, LorberB, FlorentzC, et al. (2007) Crystal structure of human mitochondrial tyrosyl-tRNA synthetase reveals common and idiosyncratic features. Structure 15: 1505–1516.

39. RileyLG, CooperS, HickeyP, Rudinger-ThirionJ, McKenzieM, et al. (2010) Mutation of the mitochondrial tyrosyl-tRNA synthetase gene, YARS2, causes myopathy, lactic acidosis, and sideroblastic anemia - MLASA syndrome. Am J Hum Genet 87: 52–59.

40. ClarosMG, VincensP (1996) Computational method to predict mitochondrially imported proteins and their targeting sequences. Eur J Biochem 241: 779–786.

41. VenkenKJ, SchulzeKL, HaeltermanNA, PanH, HeY, et al. (2011) MiMIC: a highly versatile transposon insertion resource for engineering Drosophila melanogaster genes. Nat Methods 8: 737–743.

42. AntonellisA, GreenED (2008) The role of aminoacyl-tRNA synthetases in genetic diseases. Annu Rev Genomics Hum Genet 9: 87–107.

43. LambertssonA (1998) The Minute genes in Drosophila and their molecular functions. Adv Genet 38: 69–134.

44. HowellsAJ (1972) Levels of RNA and DNA in Drosophila melanogaster at different stages of development: a comparison between one bobbed and two phenotypically non-bobbed stocks. Biochem Genet 6: 217–230.

45. StorkebaumE, Leitão-GonçalvesR, GodenschwegeT, NangleL, MejiaM, et al. (2009) Dominant mutations in the tyrosyl-tRNA synthetase gene recapitulate in Drosophila features of human Charcot-Marie-Tooth neuropathy. Proc Natl Acad Sci USA 106: 11782–11787.

46. FarnsworthMW (1965) Oxidative phosphorylation in the Minute mutants of Drosophila. J Exp Zool 160: 363–368.

47. WolskyAA (1937) Production of local depressions in the development of Drosophila pupae. Nature 139: 1069–1070.

48. XuH, DelucaS, O'farrellP (2008) Manipulating the metazoan mitochondrial genome with targeted restriction enzymes. Science 321: 575–577.

49. SchultzJ (1929) The Minute reaction in the development of Drosophila melanogaster. Genetics 14: 366–419.

50. LeeHO, DavidsonJM, DuronioRJ (2009) Endoreplication: polyploidy with purpose. Genes Dev 23: 2461–2477.

51. BrittonJS, EdgarBA (1998) Environmental control of the cell cycle in Drosophila: nutrition activates mitotic and endoreplicative cells by distinct mechanisms. Development 125: 2149–2158.

52. FergestadT, BostwickB, GanetzkyB (2006) Metabolic disruption in Drosophila bang-sensitive seizure mutants. Genetics 173: 1357–1364.

53. Fernández-AyalaDJ, ChenS, KemppainenE, O'DellKM, JacobsH (2010) Gene expression in a Drosophila model of mitochondrial disease. PLoS ONE 5: e8549 doi:10.1371/journal.pone.0008549.

54. SugiyamaS, MoritohS, FurukawaY, MizunoT, LimY, et al. (2006) Involvement of the mitochondrial protein translocator component Tim50 in growth, cell proliferation and the modulation of respiration in Drosophila. Genetics 176: 927–936.

55. MandalS, GuptanP, Owusu-AnsahE, BanerjeeU (2005) Mitochondrial regulation of cell cycle progression during development as revealed by the tenured mutation in Drosophila. Dev Cell 9: 843–854.

56. AudibertA, SimonF, GhoM (2005) Cell cycle diversity involves differential regulation of Cyclin E activity in the Drosophila bristle cell lineage. Development 132: 2287–2297.

57. OlsonJR, CooperSJ, SwansonDL, BraunMJ, WilliamsJB (2010) The relationship of metabolic performance and distribution in black-capped and Carolina chickadees. Physiol Biochem Zool 83: 263–275.

58. Lynch M (2007) The Origins of Genomic Architecture. Sunderland, MA, USA: Sinauer Associates, Inc. Publishers.

59. MontoothKL, RandDM (2008) The spectrum of mitochondrial mutation differs across species. PLoS Biol 6: e213 doi:10.1371/journal.pbio.0040213.

60. Haag-LiautardC, CoffeyN, HouleD, LynchM, CharlesworthB, et al. (2008) Direct estimation of the mitochondrial DNA mutation rate in Drosophila melanogaster. PLoS Biol 6: e204 doi:10.1371/journal.pbio.0060204.

61. EllisonCK, NiehuisO, GadauJ (2008) Hybrid breakdown and mitochondrial dysfunction in hybrids of Nasonia parasitoid wasps. J Evol Biol 21: 1844–1851.

62. OliveiraDC, RaychoudhuryR, LavrovDV, WerrenJH (2008) Rapidly evolving mitochondrial genome and directional selection in mitochondrial genes in the parasitic wasp Nasonia (hymenoptera: pteromalidae). Mol Biol Evol 25: 2167–2180.

63. ShoemakerDD, DyerKA, AhrensM, McAbeeK, JaenikeJ (2004) Decreased diversity but increased substitution rate in host mtDNA as a consequence of Wolbachia endosymbiont infection. Genetics 168: 2049–2058.

64. RötigA (2011) Human diseases with impaired mitochondrial protein synthesis. Biochim Biophys Acta 1807: 1198–1205.

65. Morgan-HughesJA, SweeneyMG, CooperJM, HammansSR, BrockingtonM, et al. (1995) Mitochondrial DNA (mtDNA) diseases: correlation of genotype to phenotype. Biochim Biophys Acta 1271: 135–140.

66. LimongelliA, SchaeferJ, JacksonS, InvernizziF, KirinoY, et al. (2004) Variable penetrance of a familial progressive necrotising encephalopathy due to a novel tRNA(Ile) homoplasmic mutation in the mitochondrial genome. J Med Genet 41: 342–349.

67. PerliE, GiordanoC, TuppenHA, MontopoliM, MontanariA, et al. (2012) Isoleucyl-tRNA synthetase levels modulate the penetrance of a homoplasmic m.4277T>C mitochondrial tRNA(Ile) mutation causing hypertrophic cardiomyopathy. Hum Mol Genet 21: 85–100.

68. FrancisciS, MontanariA, De LucaC, FrontaliL (2011) Peptides from aminoacyl-tRNA synthetases can cure the defects due to mutations in mt tRNA genes. Mitochondrion 11: 919–923.

69. The R Development Core Team (2011) R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing.

70. BromanKW, WuH, SenS, ChurchillGA (2003) R/qtl: QTL mapping in experimental crosses. Bioinformatics 19: 889–890.

71. CookR, ChristensenS, DealJ, CoburnR, DealM, et al. (2012) The generation of chromosomal deletions to provide extensive coverage and subdivision of the Drosophila melanogaster genome. Genome Biol 13: R21.

72. Drosophila 12 Genomes Consortium (2007) ClarkAG, EisenMB, SmithDR, BergmanCM, et al. (2007) Evolution of genes and genomes on the Drosophila phylogeny. Nature 450: 203–218.

73. VenkenKJT, CarlsonJW, SchulzeKL, PanH, HeY, et al. (2009) Versatile P[acman] BAC libraries for transgenesis studies in Drosophila melanogaster. Nat Methods 431–U446.

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Genetika Reprodukčná medicína

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