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Nonsense-Mediated Decay Enables Intron Gain in


Intron number varies considerably among genomes, but despite their fundamental importance, the mutational mechanisms and evolutionary processes underlying the expansion of intron number remain unknown. Here we show that Drosophila, in contrast to most eukaryotic lineages, is still undergoing a dramatic rate of intron gain. These novel introns carry significantly weaker splice sites that may impede their identification by the spliceosome. Novel introns are more likely to encode a premature termination codon (PTC), indicating that nonsense-mediated decay (NMD) functions as a backup for weak splicing of new introns. Our data suggest that new introns originate when genomic insertions with weak splice sites are hidden from selection by NMD. This mechanism reduces the sequence requirement imposed on novel introns and implies that the capacity of the spliceosome to recognize weak splice sites was a prerequisite for intron gain during eukaryotic evolution.


Vyšlo v časopise: Nonsense-Mediated Decay Enables Intron Gain in. PLoS Genet 6(1): e32767. doi:10.1371/journal.pgen.1000819
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1000819

Souhrn

Intron number varies considerably among genomes, but despite their fundamental importance, the mutational mechanisms and evolutionary processes underlying the expansion of intron number remain unknown. Here we show that Drosophila, in contrast to most eukaryotic lineages, is still undergoing a dramatic rate of intron gain. These novel introns carry significantly weaker splice sites that may impede their identification by the spliceosome. Novel introns are more likely to encode a premature termination codon (PTC), indicating that nonsense-mediated decay (NMD) functions as a backup for weak splicing of new introns. Our data suggest that new introns originate when genomic insertions with weak splice sites are hidden from selection by NMD. This mechanism reduces the sequence requirement imposed on novel introns and implies that the capacity of the spliceosome to recognize weak splice sites was a prerequisite for intron gain during eukaryotic evolution.


Zdroje

1. TarrioR

AyalaFJ

Rodriguez-TrellesF

2008 Alternative splicing: a missing piece in the puzzle of intron gain. Proc Natl Acad Sci U S A 105 7223 7228

2. Coulombe-HuntingtonJ

MajewskiJ

2007 Intron Loss and Gain in Drosophila. Molecular Biology and Evolution 24 2842 2850

3. IrimiaM

RukovJL

PennyD

VintherJ

Garcia-FernandezJ

2008 Origin of introns by ‘intronization’ of exonic sequences. Trends Genet 24 378 381

4. RaggH

KumarA

KosterK

BenteleC

WangY

2009 Multiple gains of spliceosomal introns in a superfamily of vertebrate protease inhibitor genes. BMC Evol Biol 9 208

5. Cavalier-SmithT

1991 Intron phylogeny: a new hypothesis. Trends Genet 7 145 148

6. ToorN

KeatingK

TaylorS

PyleA

2008 Crystal Structure of a Self-Spliced Group II Intron. Science 77 82

7. CataniaF

LynchM

2008 Where do introns come from? PLoS Biol 6 e283 doi:10.1371/journal.pbio.0060283

8. ZhangC

LiWH

KrainerAR

ZhangMQ

2008 RNA landscape of evolution for optimal exon and intron discrimination. Proc Natl Acad Sci U S A 105 5797 5802

9. WahlMC

WillCL

LuhrmannR

2009 The spliceosome: design principles of a dynamic RNP machine. Cell 136 701 718

10. Cavalier-SmithT

1985 Selfish DNA and the origin of introns. Nature 315 283 284

11. RoySW

IrimiaM

2009 Mystery of intron gain: new data and new models. Trends Genet 25 67 73

12. PavesiG

ZambelliF

CaggeseC

PesoleG

2008 Exalign: a new method for comparative analysis of exon-intron gene structures. Nucleic Acids Res 36 e47

13. GaoX

LynchM

2009 Ubiquitous internal gene duplication and intron creation in eukaryotes. Proc Natl Acad Sci U S A

14. Li

Tucker

Sung

Thomask

Lynch

2009 Extensive, Recent Intron Gains in Daphnia Population. Science 326 1260 1262

15. CataniaF

GaoX

ScofieldDG

2009 Endogenous mechanisms for the origins of spliceosomal introns. J Hered 100 591 596

16. SayaniS

JanisM

LeeCY

ToescaI

ChanfreauGF

2008 Widespread impact of nonsense-mediated mRNA decay on the yeast intronome. Mol Cell 31 360 370

17. HansenKD

LareauLF

BlanchetteM

GreenRE

MengQ

2009 Genome-wide identification of alternative splice forms down-regulated by nonsense-mediated mRNA decay in Drosophila. PLoS Genet 5 e1000525 doi:10.1371/journal.pgen.1000525

18. NielsenC

FriedmanB

BirrenB

BurgeC

GalaganJ

2004 Patterns of Intron Gain and Loss in Fungi. Plos Biol 2 e422 doi:10.1371/journal.pbio.0020422

19. RogozinIB

WolfYI

SorokinAV

MirkinBG

KooninEV

2003 Remarkable interkingdom conservation of intron positions and massive, lineage-specific intron loss and gain in eukaryotic evolution. Curr Biol 13 1512 1517

20. PalmerJD

LogsdonJMJr

1991 The recent origins of introns. Curr Opin Genet Dev 1 470 477

21. CrickF

1979 Split genes and RNA splicing. Science 204 264 271

22. RogersJH

1989 How were introns inserted into nuclear genes? Trends Genet 5 213 216

23. VenkateshB

NingY

BrennerS

1999 Late changes in spliceosomal introns define clades in vertebrate evolution. Proc Natl Acad Sci U S A 96 10267 10271

24. KnowlesDG

McLysaghtA

2006 High rate of recent intron gain and loss in simultaneously duplicated Arabidopsis genes. Mol Biol Evol 23 1548 1557

25. SharptonT

NeafseyD

GalaganJ

TaylorJ

2008 Mechanisms of intron gain and loss in Cryptococcus. Genome Biol 9 R24

26. FedorovA

RoyS

FedorovaL

GilbertW

2003 Mystery of intron gain. Genome Res 13 2236 2241

27. Hazkani-CovoE

CovoS

2008 Numt-mediated double-strand break repair mitigates deletions during primate genome evolution. PLoS Genet 4 e1000237 doi:10.1371/journal.pgen.1000237

28. TanayA

SiggiaED

2008 Sequence context affects the rate of short insertions and deletions in flies and primates. Genome Biol 9 R37

29. RocaX

SachidanandamR

KrainerAR

2005 Determinants of the inherent strength of human 5′ splice sites. Rna 11 683 698

30. FreundM

HicksMJ

KonermannC

OtteM

HertelKJ

2005 Extended base pair complementarity between U1 snRNA and the 5′ splice site does not inhibit splicing in higher eukaryotes, but rather increases 5′ splice site recognition. Nucleic Acids Res 33 5112 5119

31. DingW

LinL

RenF

ZouH

DuanZ

2009 Effects of splice sites on the intron retention in histamine H3 receptors from rats and mice. J Genet Genomics 36 475 482

32. JaillonO

BouhoucheK

GoutJ

AuryJ

NoelB

2008 Translational control of intron splicing in eukaryotes. Nature 451 359 362

33. BrognaS

WenJ

2009 Nonsense-mediated mRNA decay (NMD) mechanisms. Nat Struct Mol Biol 16 107 113

34. StalderL

MuhlemannO

2008 The meaning of nonsense. Trends Cell Biol 18 315 321

35. JeffaresD

MourierT

PennyD

2006 The biology of intron gain and loss. Trends in Genetics 22 16 22

36. LinH

ZhuW

SilvaJ

GuX

BuellC

2006 Intron gain and loss in segmentally duplicated genes in rice. Genome Biol 7 R41

37. ChenJQ

WuY

YangH

BergelsonJ

KreitmanM

2009 Variation in the ratio of nucleotide substitution and indel rates across genomes in mammals and bacteria. Mol Biol Evol 26 1523 1531

38. HahnM

HanM

HanS

2007 Gene Family Evolution across 12 Drosophila Genomes. PLoS Genet 3 e197 doi:10.1371/journal.pgen.0030197

39. BirneyE

ClampM

DurbinR

2004 GeneWise and Genomewise. Genome Res 14 988 995

40. CsurosM

HoleyJ

RogozinI

2007 In search of lost introns. Bioinformatics 23 i87 i96

41. RoySW

GilbertW

2005 Rates of intron loss and gain: implications for early eukaryotic evolution. Proc Natl Acad Sci U S A 102 5773 5778

42. StajichJE

DietrichFS

RoySW

2007 Comparative genomic analysis of fungal genomes reveals intron-rich ancestors. Genome Biol 8 R223

43. StephensRM

SchneiderTD

1992 Features of spliceosome evolution and function inferred from an analysis of the information at human splice sites. J Mol Biol 228 1124 1136

44. IrimiaM

RoySW

2008 Evolutionary convergence on highly-conserved 3′ intron structures in intron-poor eukaryotes and insights into the ancestral eukaryotic genome. PLoS Genet 4 e1000148 doi:10.1371/journal.pgen.1000148

45. HillerM

PlatzerM

2008 Widespread and subtle: alternative splicing at short-distance tandem sites. Trends in Genetics 24 246 255

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Genetika Reprodukčná medicína

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PLOS Genetics


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