Function and Evolution of DNA Methylation in
The parasitoid wasp Nasonia vitripennis is an emerging genetic model for functional analysis of DNA methylation. Here, we characterize genome-wide methylation at a base-pair resolution, and compare these results to gene expression across five developmental stages and to methylation patterns reported in other insects. An accurate assessment of DNA methylation across the genome is accomplished using bisulfite sequencing of adult females from a highly inbred line. One-third of genes show extensive methylation over the gene body, yet methylated DNA is not found in non-coding regions and rarely in transposons. Methylated genes occur in small clusters across the genome. Methylation demarcates exon-intron boundaries, with elevated levels over exons, primarily in the 5′ regions of genes. It is also elevated near the sites of translational initiation and termination, with reduced levels in 5′ and 3′ UTRs. Methylated genes have higher median expression levels and lower expression variation across development stages than non-methylated genes. There is no difference in frequency of differential splicing between methylated and non-methylated genes, and as yet no established role for methylation in regulating alternative splicing in Nasonia. Phylogenetic comparisons indicate that many genes maintain methylation status across long evolutionary time scales. Nasonia methylated genes are more likely to be conserved in insects, but even those that are not conserved show broader expression across development than comparable non-methylated genes. Finally, examination of duplicated genes shows that those paralogs that have lost methylation in the Nasonia lineage following gene duplication evolve more rapidly, show decreased median expression levels, and increased specialization in expression across development. Methylation of Nasonia genes signals constitutive transcription across developmental stages, whereas non-methylated genes show more dynamic developmental expression patterns. We speculate that loss of methylation may result in increased developmental specialization in evolution and acquisition of methylation may lead to broader constitutive expression.
Vyšlo v časopise:
Function and Evolution of DNA Methylation in. PLoS Genet 9(10): e32767. doi:10.1371/journal.pgen.1003872
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1003872
Souhrn
The parasitoid wasp Nasonia vitripennis is an emerging genetic model for functional analysis of DNA methylation. Here, we characterize genome-wide methylation at a base-pair resolution, and compare these results to gene expression across five developmental stages and to methylation patterns reported in other insects. An accurate assessment of DNA methylation across the genome is accomplished using bisulfite sequencing of adult females from a highly inbred line. One-third of genes show extensive methylation over the gene body, yet methylated DNA is not found in non-coding regions and rarely in transposons. Methylated genes occur in small clusters across the genome. Methylation demarcates exon-intron boundaries, with elevated levels over exons, primarily in the 5′ regions of genes. It is also elevated near the sites of translational initiation and termination, with reduced levels in 5′ and 3′ UTRs. Methylated genes have higher median expression levels and lower expression variation across development stages than non-methylated genes. There is no difference in frequency of differential splicing between methylated and non-methylated genes, and as yet no established role for methylation in regulating alternative splicing in Nasonia. Phylogenetic comparisons indicate that many genes maintain methylation status across long evolutionary time scales. Nasonia methylated genes are more likely to be conserved in insects, but even those that are not conserved show broader expression across development than comparable non-methylated genes. Finally, examination of duplicated genes shows that those paralogs that have lost methylation in the Nasonia lineage following gene duplication evolve more rapidly, show decreased median expression levels, and increased specialization in expression across development. Methylation of Nasonia genes signals constitutive transcription across developmental stages, whereas non-methylated genes show more dynamic developmental expression patterns. We speculate that loss of methylation may result in increased developmental specialization in evolution and acquisition of methylation may lead to broader constitutive expression.
Zdroje
1. HeXJ, ChenT, ZhuJK (2011) Regulation and function of DNA methylation in plants and animals. Cell Res 21: 442–465.
2. JonesPA (2012) Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet 13: 484–492.
3. KloseRJ, BirdAP (2006) Genomic DNA methylation: the mark and its mediators. Trends Biochem Sci 31: 89–97.
4. SuzukiMM, BirdA (2008) DNA methylation landscapes: provocative insights from epigenomics. Nat Rev Genet 9: 465–476.
5. BirdA (2002) DNA methylation patterns and epigenetic memory. Genes Dev 16: 6–21.
6. PaulsenM, Ferguson-SmithAC (2001) DNA methylation in genomic imprinting, development, and disease. J Pathol 195: 97–110.
7. HellmanA, ChessA (2007) Gene body-specific methylation on the active X chromosome. Science 315: 1141–1143.
8. NorrisDP, BrockdorffN, RastanS (1991) Methylation status of CpG-rich islands on active and inactive mouse X chromosomes. Mamm Genome 1: 78–83.
9. ListerR, MukamelEA, NeryJR, UrichM, PuddifootCA, et al. (2013) Global Epigenomic Reconfiguration During Mammalian Brain Development. Science 341 (6146) 1237905.
10. Gardiner-GardenM, FrommerM (1987) CpG islands in vertebrate genomes. J Mol Biol 196: 261–282.
11. AntequeraF, BirdA (1993) Number of CpG islands and genes in human and mouse. Proc Natl Acad Sci U S A 90: 11995–11999.
12. DeatonAM, BirdA (2011) CpG islands and the regulation of transcription. Genes Dev 25: 1010–1022.
13. JonesPA, TakaiD (2001) The role of DNA methylation in mammalian epigenetics. Science 293: 1068–1070.
14. ListerR, PelizzolaM, DowenRH, HawkinsRD, HonG, et al. (2009) Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 462: 315–322.
15. ZemachA, McDanielIE, SilvaP, ZilbermanD (2010) Genome-wide evolutionary analysis of eukaryotic DNA methylation. Science 328: 916–919.
16. GlastadKM, HuntBG, YiSV, GoodismanMA (2011) DNA methylation in insects: on the brink of the epigenomic era. Insect Mol Biol 20: 553–565.
17. GaveryMR, RobertsSB (2010) DNA methylation patterns provide insight into epigenetic regulation in the Pacific oyster (Crassostrea gigas). BMC Genomics 11: 483.
18. BonasioR, LiQ, LianJ, MuttiNS, JinL, et al. (2012) Genome-wide and Caste-Specific DNA Methylomes of the Ants Camponotus floridanus and Harpegnathos saltator. Curr Biol 22: 1755–1764.
19. LykoF, ForetS, KucharskiR, WolfS, FalckenhaynC, et al. (2010) The honey bee epigenomes: differential methylation of brain DNA in queens and workers. PLoS Biol 8: e1000506.
20. ParkJ, PengZ, ZengJ, ElangoN, ParkT, et al. (2011) Comparative analyses of DNA methylation and sequence evolution using Nasonia genomes. Mol Biol Evol 28: 3345–3354.
21. WurmY, WangJ, Riba-GrognuzO, CoronaM, NygaardS, et al. (2011) The genome of the fire ant Solenopsis invicta. Proc Natl Acad Sci U S A 108: 5679–5684.
22. XiangH, ZhuJ, ChenQ, DaiF, LiX, et al. (2010) Single base-resolution methylome of the silkworm reveals a sparse epigenomic map. Nat Biotechnol 28: 516–520.
23. GaoF, LiuX, WuXP, WangXL, GongD, et al. (2012) Differential DNA methylation in discrete developmental stages of the parasitic nematode Trichinella spiralis. Genome Biol 13: R100.
24. TweedieS, CharltonJ, ClarkV, BirdA (1997) Methylation of genomes and genes at the invertebrate-vertebrate boundary. Mol Cell Biol 17: 1469–1475.
25. BrachtJR, PerlmanDH, LandweberLF (2012) Cytosine methylation and hydroxymethylation mark DNA for elimination in Oxytricha trifallax. Genome Biol 13: R99.
26. WalshTK, BrissonJA, RobertsonHM, GordonK, Jaubert-PossamaiS, et al. (2010) A functional DNA methylation system in the pea aphid, Acyrthosiphon pisum. Insect Mol Biol 19 Suppl 2: 215–228.
27. SardaS, ZengJ, HuntBG, YiSV (2012) The Evolution of Invertebrate Gene Body Methylation. Mol Biol Evol 29: 1907–16.
28. ForetS, KucharskiR, PittelkowY, LockettGA, MaleszkaR (2009) Epigenetic regulation of the honey bee transcriptome: unravelling the nature of methylated genes. BMC Genomics 10: 472.
29. ElangoN, HuntBG, GoodismanMA, YiSV (2009) DNA methylation is widespread and associated with differential gene expression in castes of the honeybee, Apis mellifera. Proc Natl Acad Sci U S A 106: 11206–11211.
30. SimpsonVJ, JohnsonTE, HammenRF (1986) Caenorhabditis elegans DNA does not contain 5-methylcytosine at any time during development or aging. Nucleic Acids Res 14: 6711–6719.
31. RaddatzG, GuzzardoPM, OlovaN, FantappieMR, RamppM, et al. (2013) Dnmt2-dependent methylomes lack defined DNA methylation patterns. Proc Natl Acad Sci U S A 110: 8627–8631.
32. LykoF, RamsahoyeBH, JaenischR (2000) DNA methylation in Drosophila melanogaster. Nature 408: 538–540.
33. GowherH, LeismannO, JeltschA (2000) DNA of Drosophila melanogaster contains 5-methylcytosine. EMBO J 19: 6918–6923.
34. WerrenJH, RichardsS, DesjardinsCA, NiehuisO, GadauJ, et al. (2010) Functional and evolutionary insights from the genomes of three parasitoid Nasonia species. Science 327: 343–348.
35. SrinivasanDG, BrissonJA (2012) Aphids: a model for polyphenism and epigenetics. Genet Res Int 2012: 431531.
36. Insights into social insects from the genome of the honeybee Apis mellifera. Nature 443: 931–949.
37. SmithCR, SmithCD, RobertsonHM, HelmkampfM, ZiminA, et al. (2011) Draft genome of the red harvester ant Pogonomyrmex barbatus. Proc Natl Acad Sci U S A 108: 5667–5672.
38. HuntBG, GlastadKM, YiSV, GoodismanMA (2013) Patterning and regulatory associations of DNA methylation are mirrored by histone modifications in insects. Genome Biol Evol 5: 591–598.
39. FloresKB, WolschinF, AllenAN, CorneveauxJJ, HuentelmanM, et al. (2012) Genome-wide association between DNA methylation and alternative splicing in an invertebrate. BMC Genomics 13: 480.
40. BeukeboomL, DesplanC (2003) Nasonia. Curr Biol 13: R860.
41. WerrenJH, LoehlinDW (2009) The parasitoid wasp Nasonia: an emerging model system with haploid male genetics. Cold Spring Harb Protoc 2009: pdb emo134.
42. Munoz-TorresMC, ReeseJT, ChildersCP, BennettAK, SundaramJP, et al. (2011) Hymenoptera Genome Database: integrated community resources for insect species of the order Hymenoptera. Nucleic Acids Res 39: D658–662.
43. SazeH, TsuganeK, KannoT, NishimuraT (2012) DNA methylation in plants: relationship to small RNAs and histone modifications, and functions in transposon inactivation. Plant Cell Physiol 53: 766–784.
44. HartiganJA, HartiganPM (1985) The Dip Test of Unimodality. Annals of Statistics 13: 70–84.
45. HartiganPM (1985) Computation of the Dip Statistic to Test for Unimodality. Applied Statistics-Journal of the Royal Statistical Society Series C 34: 320–325.
46. WaterhouseRM, TegenfeldtF, LiJ, ZdobnovEM, KriventsevaEV (2013) OrthoDB: a hierarchical catalog of animal, fungal and bacterial orthologs. Nucleic Acids Res 41: D358–365.
47. AndersenPK, JensenTH (2010) A pause to splice. Mol Cell 40: 503–505.
48. MeyerKD, SaletoreY, ZumboP, ElementoO, MasonCE, et al. (2012) Comprehensive analysis of mRNA methylation reveals enrichment in 3′ UTRs and near stop codons. Cell 149: 1635–1646.
49. ZengJ, YiSV (2010) DNA methylation and genome evolution in honeybee: gene length, expression, functional enrichment covary with the evolutionary signature of DNA methylation. Genome Biol Evol 2: 770–780.
50. WolffeAP, MatzkeMA (1999) Epigenetics: regulation through repression. Science 286: 481–486.
51. WeberM, HellmannI, StadlerMB, RamosL, PaaboS, et al. (2007) Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome. Nat Genet 39: 457–466.
52. SimolaDF, WisslerL, DonahueG, WaterhouseRM, HelmkampfM, et al. (2013) Social insect genomes exhibit dramatic evolution in gene composition and regulation while preserving regulatory features linked to sociality. Genome Res 23: 1235–1247.
53. HerbBR, WolschinF, HansenKD, AryeeMJ, LangmeadB, et al. (2012) Reversible switching between epigenetic states in honeybee behavioral subcastes. Nat Neurosci 15: 1371–1373.
54. LoehlinDW, WerrenJH (2012) Evolution of shape by multiple regulatory changes to a growth gene. Science 335: 943–947.
55. NiehuisO, BuellesbachJ, GibsonJD, PothmannD, HannerC, et al. (2013) Behavioural and genetic analyses of Nasonia shed light on the evolution of sex pheromones. Nature 494: 345–348.
56. LiH, DurbinR (2009) Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25: 1754–1760.
57. TrapnellC, PachterL, SalzbergSL (2009) TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25: 1105–1111.
58. TrapnellC, WilliamsBA, PerteaG, MortazaviA, KwanG, et al. (2010) Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat Biotechnol 28: 511–515.
59. ThorvaldsdottirH, RobinsonJT, MesirovJP (2012) Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration. Brief Bioinform 14: 178–92.
60. RobinsonJT, ThorvaldsdottirH, WincklerW, GuttmanM, LanderES, et al. (2011) Integrative genomics viewer. Nat Biotechnol 29: 24–26.
61. GentlemanRC, CareyVJ, BatesDM, BolstadB, DettlingM, et al. (2004) Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 5: R80.
62. ConesaA, GotzS, Garcia-GomezJM, TerolJ, TalonM, et al. (2005) Blast2GO: a universal tool for annotation, visualization and analysis in functional genomics research. Bioinformatics 21: 3674–3676.
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2013 Číslo 10
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
Najčítanejšie v tomto čísle
- Dominant Mutations in Identify the Mlh1-Pms1 Endonuclease Active Site and an Exonuclease 1-Independent Mismatch Repair Pathway
- Eleven Candidate Susceptibility Genes for Common Familial Colorectal Cancer
- The Histone H3 K27 Methyltransferase KMT6 Regulates Development and Expression of Secondary Metabolite Gene Clusters
- The Integrator Complex Subunit 6 (Ints6) Confines the Dorsal Organizer in Vertebrate Embryogenesis