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Duplication Hotspots Are Associated with Late-Replicating Regions of the Genome


Duplications play a significant role in both extremes of the phenotypic spectrum of newly arising mutations: they can have severe deleterious effects (e.g. duplications underlie a variety of diseases) but can also be highly advantageous. The phenotypic potential of newly arisen duplications has stimulated wide interest in both the mutational and selective processes shaping these variants in the genome. Here we take advantage of the Drosophila simulansDrosophila melanogaster genetic system to further our understanding of both processes. Regarding mutational processes, the study of two closely related species allows investigation of the potential existence of shared duplication hotspots, and the similarities and differences between the two genomes can be used to dissect its underlying causes. Regarding selection, the difference in the effective population size between the two species can be leveraged to ask questions about the strength of selection acting on different classes of duplications. In this study, we conducted a survey of duplication polymorphisms in 14 different lines of D. simulans using tiling microarrays and combined it with an analogous survey for the D. melanogaster genome. By integrating the two datasets, we identified duplication hotspots conserved between the two species. However, unlike the duplication hotspots identified in mammalian genomes, Drosophila duplication hotspots are not associated with sequences of high sequence identity capable of mediating non-allelic homologous recombination. Instead, Drosophila duplication hotspots are associated with late-replicating regions of the genome, suggesting a link between DNA replication and duplication rates. We also found evidence supporting a higher effectiveness of selection on duplications in D. simulans than in D. melanogaster. This is also true for duplications segregating at high frequency, where we find evidence in D. simulans that a sizeable fraction of these mutations is being driven to fixation by positive selection.


Vyšlo v časopise: Duplication Hotspots Are Associated with Late-Replicating Regions of the Genome. PLoS Genet 7(11): e32767. doi:10.1371/journal.pgen.1002340
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002340

Souhrn

Duplications play a significant role in both extremes of the phenotypic spectrum of newly arising mutations: they can have severe deleterious effects (e.g. duplications underlie a variety of diseases) but can also be highly advantageous. The phenotypic potential of newly arisen duplications has stimulated wide interest in both the mutational and selective processes shaping these variants in the genome. Here we take advantage of the Drosophila simulansDrosophila melanogaster genetic system to further our understanding of both processes. Regarding mutational processes, the study of two closely related species allows investigation of the potential existence of shared duplication hotspots, and the similarities and differences between the two genomes can be used to dissect its underlying causes. Regarding selection, the difference in the effective population size between the two species can be leveraged to ask questions about the strength of selection acting on different classes of duplications. In this study, we conducted a survey of duplication polymorphisms in 14 different lines of D. simulans using tiling microarrays and combined it with an analogous survey for the D. melanogaster genome. By integrating the two datasets, we identified duplication hotspots conserved between the two species. However, unlike the duplication hotspots identified in mammalian genomes, Drosophila duplication hotspots are not associated with sequences of high sequence identity capable of mediating non-allelic homologous recombination. Instead, Drosophila duplication hotspots are associated with late-replicating regions of the genome, suggesting a link between DNA replication and duplication rates. We also found evidence supporting a higher effectiveness of selection on duplications in D. simulans than in D. melanogaster. This is also true for duplications segregating at high frequency, where we find evidence in D. simulans that a sizeable fraction of these mutations is being driven to fixation by positive selection.


Zdroje

1. SebatJLakshmiBTrogeJAlexanderJYoungJ 2004 Large-scale copy number polymorphism in the human genome. Science 305 525 528

2. IafrateAJFeukLRiveraMNListewnikMLDonahoePK 2004 Detection of large-scale variation in the human genome. Nat Genet 35 949 951

3. InoueKLupskiJR 2002 Molecular mechanisms for genomic disorders. Annu Rev Genomics Hum Genet 3 199 242

4. GuWZhangFLupskiJR 2008 Mechanisms for human genomic rearrangements. Pathogenetics 1 4

5. SebatJLakshmiBMalhotraDTrogeJLese-MartinC 2007 Strong association of de novo copy number mutations with autism. Science 316 445 449

6. XuBRoosJLLevySvan RensburgEJGogosJA 2008 Strong association of de novo copy number mutations with sporadic schizophrenia. Nat Genet 40 880 885

7. McCarrollSAHuettAKuballaPChilewskiSDLandryA 2008 Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn's disease. Nat Genet 40 1107 1112

8. de CidRRiveira-MunozEZeeuwenPLRobargeJLiaoW 2009 Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility factor for psoriasis. Nat Genet 41 211 215

9. WillerCJSpeliotesEKLoosRJLiSLindgrenCM 2009 Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet 41 25 34

10. PerryGHDominyNJClawKGLeeASFieglerH 2007 Diet and the evolution of human amylase gene copy number variation. Nat Genet 39 1256 1260

11. LongMBetránEThorntonKWangW 2003 The origin of new genes: glimpses from the young and old. Nat Rev Genet 4 865 875

12. TaylorJSRaesJ 2004 Duplication and divergence: the evolution of new genes and old ideas. Annu Rev Genet 38 615 643

13. KaessmannH 2010 Origins, evolution, and phenotypic impact of new genes. Genome Res 20 1313 1326

14. Cardoso-MoreiraMLongM 2011 The origin and evolution of new genes. Evolutionary genomics: statistical and computational methods Springer (Humana). In press

15. Rosengren PielbergGGolovkoASundströmECurikILennartssonJ 2008 A cis-acting regulatory mutation causes premature hair graying and susceptibility to melanoma in the horse. Nat Genet 40 1004 1009

16. WrightDBoijeHMeadowsJRBed'homBGourichonD 2009 Copy number variation in intron 1 of SOX5 causes the Pea-comb phenotype in chickens. PLoS Genet 5 e1000512 doi:10.1371/journal.pgen.1000512

17. ParkerHGVonHoldtBMQuignonPMarguliesEHShaoS 2009 An expressed fgf4 retrogene is associated with breed-defining chondrodysplasia in domestic dogs. Science 325 995 998

18. SankaranarayananKWassomJS 2005 Ionizing radiation and genetic risks XIV. Potential research directions in the post-genome era based on knowledge of repair of radiation-induced DNA double-strand breaks in mammalian somatic cells and the origin of deletions associated with human genomic disorders. Mutat Res 578 333 370

19. AguileraAGómez-GonzálezB 2008 Genome instability: a mechanistic view of its causes and consequences. Nat Rev Genet 9 204 217

20. LeeJACarvalhoCMLupskiJR 2007 A DNA replication mechanism for generating nonrecurrent rearrangements associated with genomic disorders. Cell 131 1236 1247

21. HastingsPJIraGLupskiJR 2009 A microhomology-mediated break-induced replication model for the origin of human copy number variation. PLoS Genet 5 e1000327 doi:10.1371/journal.pgen.1000327

22. HastingsPJLupskiJRRosenbergSMIraG 2009 Mechanisms of change in gene copy number. Nat Rev Genet 10 551 564

23. ChenJMChuzhanovaNStensonPDFérecCCooperDN 2005 Meta-analysis of gross insertions causing human genetic disease: novel mutational mechanisms and the role of replication slippage. Hum Mutat 25 207 221

24. ArltMFMulleJGSchaibleyVMRaglandRLDurkinSG 2009 Replication stress induces genome-wide copy number changes in human cells that resemble polymorphic and pathogenic variants. Am J Hum Genet 84 339 360

25. ChenJMCooperDNFérecCKehrer-SawatzkiHPatrinosGP 2010 Genomic rearrangements in inherited disease and cancer. Semin Cancer Biol 20 222 233

26. LupskiJR 2007 Genomic rearrangements and sporadic disease. Nat Genet 39 S43 47

27. TurnerDJMirettiMRajanDFieglerHCarterNP 2008 Germline rates of de novo meiotic deletions and duplications causing several genomic disorders. Nat Genet 40 90 95

28. PerryGHTchindaJMcGrathSDZhangJPickerSR 2006 Hotspots for copy number variation in chimpanzees and humans. Proc Natl Acad Sci U S A 103 8006 8011

29. FuWZhangFWangYGuXJinL 2010 Identification of copy number variation hotspots in human populations. Am J Hum Genet 87 494 504

30. PerryGHYangFMarques-BonetTMurphyCFitzgeraldT 2008 Copy number variation and evolution in humans and chimpanzees. Genome Res 18 1698 1710

31. EganCMSridharSWiglerMHallIM 2007 Recurrent DNA copy number variation in the laboratory mouse. Nat Genet 39 1384 1389

32. DopmanEBHartlDL 2007 A portrait of copy-number polymorphism in Drosophila melanogaster. Proc Natl Acad Sci U S A 104 19920 19925

33. Cardoso-MoreiraMLongM 2010 Mutational bias shaping fly copy number variation: implications for genome evolution. Trends Genet 26 243 247

34. CridlandJMThorntonKR 2010 Validation of rearrangement break points identified by paired-end sequencing in natural populations of Drosophila melanogaster. Genome Biol Evol 2 83 101

35. SharpAJHansenSSelzerRRChengZReganR 2006 Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome. Nat Genet 38 1038 1042

36. EmersonJJCardoso-MoreiraMBorevitzJOLongM 2008 Natural selection shapes genome-wide patterns of copy-number polymorphism in Drosophila melanogaster. Science 320 1629 1631

37. ConradDFPintoDRedonRFeukLGokcumenO 2010 Origins and functional impact of copy number variation in the human genome. Nature 464 704 712

38. GonzalezEKulkarniHBolivarHManganoASanchezR 2005 The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility. Science 307 1434 1440

39. SchmidtJMGoodRTAppletonBSherrardJRaymantGC 2010 Copy number variation and transposable elements feature in recent, ongoing adaptation at the Cyp6g1 locus. PLoS Genet 6 e1000998 doi:10.1371/journal.pgen.1000998

40. NguyenDQWebberCHehir-KwaJPfundtRVeltmanJ 2008 Reduced purifying selection prevails over positive selection in human copy number variant evolution. Genome Res 18 1711 1723

41. PollackJRSørlieTPerouCMReesCAJeffreySS 2002 Microarray analysis reveals a major direct role of DNA copy number alteration in the transcriptional program of human breast tumors. Proc Natl Acad Sci U S A 99 12963 12968

42. KuwadaY 1911 Meiosis in the pollen mother cells of Zea Mays L.. Bot Mag 25 163 181

43. InnanHKondrashovF 2010 The evolution of gene duplications: classifying and distinguishing between models. Nat Rev Genet 11 97 108

44. WalshB 2003 Population-genetic models of the fates of duplicate genes. Genetica 118 279 294

45. BegunDJHollowayAKStevensKHillierLWPohYP 2007 Population genomics: whole-genome analysis of polymorphism and divergence in Drosophila simulans. PLoS Biol 5 e310 doi:10.1371/journal.pbio.0050310

46. CapyPGibertP 2004 Drosophila melanogaster, Drosophila simulans: so similar yet so different. Genetica 120 5 16

47. AshburnerMLemeunierF 1976 Relationships within the melanogaster species subgroup of the genus Drosophila (Sophophora) i. inversion polymorphisms in Drosophila melanogaster and Drosophila simulans. Proc R Soc Lond B Biol Sci 193 137 157

48. AulardSMontiLChaminadeNLemeunierF 2004 Mitotic and polytene chromosomes: comparisons between Drosophila melanogaster and Drosophila simulans. Genetica 120 137 150

49. AndolfattoP 2001 Contrasting patterns of X-linked and autosomal nucleotide variation in Drosophila melanogaster and Drosophila simulans. Mol Biol Evol 18 279 290

50. Eyre-WalkerAKeightleyPDSmithNGGaffneyD 2002 Quantifying the slightly deleterious mutation model of molecular evolution. Mol Biol Evol 19 2142 2149

51. HaddrillPRBachtrogDAndolfattoP 2008 Positive and negative selection on noncoding DNA in Drosophila simulans. Mol Biol Evol 25 1825 1834

52. ZhouQZhangGZhangYXuSZhaoR 2008 On the origin of new genes in Drosophila. Genome Res 18 1446 1455

53. SchriderDRHahnMW 2010 Gene copy-number polymorphism in nature. Proc Biol Sci 277 3213 3221

54. BourguetDGuillemaudTChevillonCRaymondM 2004 Fitness costs of insecticide resistance in natural breeding sites of the mosquito Culex pipiens. Evolution 58 128 135

55. ClarkAGEisenMBSmithDRBergmanCM Drosophila 12 Genomes Consortium 2007 Evolution of genes and genomes on the Drosophila phylogeny. Nature 450 203 218

56. VicosoBCharlesworthB 2006 Evolution on the X chromosome: unusual patterns and processes. Nat Rev Genet 7 645 653

57. WallJDAndolfattoPPrzeworskiM 2002 Testing models of selection and demography in Drosophila simulans. Genetics 162 203 216

58. ClarkAG 1997 Neutral behavior of shared polymorphism. Proc Natl Acad Sci U S A 94 7730 7734

59. KreitmanM 1983 Nucleotide polymorphism at the alcohol dehydrogenase locus of Drosophila melanogaster. Nature 304 412 417

60. Fiston-LavierASAnxolabehereDQuesnevilleH 2007 A model of segmental duplication formation in Drosophila melanogaster. Genome Res 17 1458 1470

61. BergmanCMQuesnevilleHAnxolabéhèreDAshburnerM 2006 Recurrent insertion and duplication generate networks of transposable element sequences in the Drosophila melanogaster genome. Genome Biol 7 R112

62. SchwaigerMStadlerMBBellOKohlerHOakeleyEJ 2009 Chromatin state marks cell-type- and gender-specific replication of the Drosophila genome. Genes Dev 23 589 601

63. EatonMLPrinzJAMacAlpineHKTretyakovGKharchenkoPV 2011 Chromatin signatures of the Drosophila replication program. Genome Res 21 164 174

64. KoszulRCaburetSDujonBFischerG 2004 Eucaryotic genome evolution through the spontaneous duplication of large chromosomal segments. EMBO J 23 234 243

65. LairdCJaffeEKarpenGLambMNelsonR 1987 Fragile sites in human chromosomes as regions of late-replicating DNA. Trends Genet 3 274 281

66. Le BeauMMRassoolFVNeillyMEEspinosa R3rdGloverTW 1998 Replication of a common fragile site, FRA3B, occurs late in S phase and is delayed further upon induction: implications for the mechanism of fragile site induction. Hum Mol Genet 7 755 761

67. ArltMFDurkinSGRaglandRLGloverTW 2006 Common fragile sites as targets for chromosome rearrangements. DNA Repair (Amst) 5 1126 1136

68. BignellGRGreenmanCDDaviesHButlerAPEdkinsS 2010 Signatures of mutation and selection in the cancer genome. Nature 463 893 898

69. LetessierAMillotGAKoundrioukoffSLachagèsAMVogtN 2011 Cell-type-specific replication initiation programs set fragility of the FRA3B fragile site. Nature 470 120 123

70. ArltMFOzdemirACBirkelandSRLyons RHJrGloverTW 2011 Comparison of constitutional and replication stress-induced genome structural variation by SNP array and mate-pair sequencing. Genetics 187 675 683

71. McBrideCSArguelloJR 2007 Five Drosophila genomes reveal nonneutral evolution and the signature of host specialization in the chemoreceptor superfamily. Genetics 177 1395 1416

72. AguadéM 2009 Nucleotide and copy-number polymorphism at the odorant receptor genes Or22a and Or22b in Drosophila melanogaster. Mol Biol Evol 26 61 70

73. KimuraM 1983 The Neutral Theory of Molecular Evolution. Cambridge Cambridge Univ. Press

74. AkashiH 1995 Inferring weak selection from patterns of polymorphism and divergence at “silent” sites in Drosophila DNA. Genetics 139 1067 1076

75. MooreRCPuruggananMD 2003 The early stages of duplicate gene evolution. Proc Natl Acad Sci U S A 100 15682 15687

76. InnanH 2009 Population genetic models of duplicated genes. Genetica 137 19 37

77. SellaGPetrovDAPrzeworskiMAndolfattoP 2009 Pervasive natural selection in the Drosophila genome? PLoS Genet 5 e1000495 doi:10.1371/journal.pgen.1000495

78. ZhangZSchwartzSWagnerLMillerW 2000 A greedy algorithm for aligning DNA sequences. J Comput Biol 7 203 214

79. QuinlanARHallIM 2010 BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26 841 842

80. KentWJ 2002 BLAT - the BLAST-like alignment tool. Genome Res 12 656 664

81. LyneRSmithRRutherfordKWakelingMVarleyA 2007 FlyMine: an integrated database for Drosophila and Anopheles genomics. Genome Biol 8 R129

82. EdenENavonRSteinfeldILipsonDYakhiniZ 2009 GOrilla: A Tool For Discovery And Visualization of Enriched GO Terms in Ranked Gene Lists. BMC Bioinformatics 10 48

83. R Development Core Team 2008 R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing. (http://www.R-project.org/)

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Genetika Reprodukčná medicína

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