Toxic Y chromosome: Increased repeat expression and age-associated heterochromatin loss in male Drosophila with a young Y chromosome
Autoři:
Alison H. Nguyen aff001; Doris Bachtrog aff001
Působiště autorů:
Department of Integrative Biology, University of California Berkeley, Berkeley, California, United States of America
aff001
Vyšlo v časopise:
Toxic Y chromosome: Increased repeat expression and age-associated heterochromatin loss in male Drosophila with a young Y chromosome. PLoS Genet 17(4): e1009438. doi:10.1371/journal.pgen.1009438
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1009438
Souhrn
Sex-specific differences in lifespan are prevalent across the tree of life and influenced by heteromorphic sex chromosomes. In species with XY sex chromosomes, females often outlive males. Males and females can differ in their overall repeat content due to the repetitive Y chromosome, and repeats on the Y might lower survival of the heterogametic sex (toxic Y effect). Here, we take advantage of the well-assembled young Y chromosome of Drosophila miranda to study the sex-specific dynamics of chromatin structure and repeat expression during aging in male and female flies. Male D. miranda have about twice as much repetitive DNA compared to females, and live shorter than females. Heterochromatin is crucial for silencing of repetitive elements, yet old D. miranda flies lose H3K9me3 modifications in their pericentromere, with heterochromatin loss being more severe during aging in males than females. Satellite DNA becomes de-repressed more rapidly in old vs. young male flies relative to females. In contrast to what is observed in D. melanogaster, we find that transposable elements (TEs) are expressed at higher levels in male D. miranda throughout their life. We show that epigenetic silencing via heterochromatin formation is ineffective on the TE-rich neo-Y chromosome, presumably due to active transcription of a large number of neo-Y linked genes, resulting in up-regulation of Y-linked TEs already in young males. This is consistent with an interaction between the evolutionary age of the Y chromosome and the genomic effects of aging. Our data support growing evidence that “toxic Y chromosomes” can diminish male fitness and a reduction in heterochromatin can contribute to sex-specific aging.
Klíčová slova:
Aging – Autosomes – Drosophila melanogaster – Heterochromatin – Invertebrate genomics – Satellite DNA – Sex chromosomes – Y chromosomes
Zdroje
1. Tarka M, Guenther A, Niemelä PT, Nakagawa S, Noble DWA. Sex differences in life history, behavior, and physiology along a slow-fast continuum: a meta-analysis. Behav Ecol Sociobiol 2018; 72:132–13. doi: 10.1007/s00265-018-2534-2 30100667
2. Maklakov AA, Lummaa V. Evolution of sex differences in lifespan and aging: causes and constraints. Bioessays. 2013; 35:717–724. doi: 10.1002/bies.201300021 23733656
3. Xirocostas ZA, Everingham SE, Moles AT. The sex with the reduced sex chromosome dies earlier: a comparison across the tree of life. Biol Lett. 2020; 16:20190867. doi: 10.1098/rsbl.2019.0867 32126186
4. Pipoly I, Bókony V, Kirkpatrick M, Donald PF, Székely T, Liker A. The genetic sex-determination system predicts adult sex ratios in tetrapods. Nature. 2015; 527:91–94. doi: 10.1038/nature15380 26444239
5. Larson K, Yan S-J, Tsurumi A, Liu J, Zhou J, Gaur K, Guo D, Eickbush TH, Li WX. Heterochromatin formation promotes longevity and represses ribosomal RNA synthesis. PLoS Genet. 2012; 8:e1002473. doi: 10.1371/journal.pgen.1002473 22291607
6. Haithcock E, Dayani Y, Neufeld E, Zahand AJ, Feinstein N, Mattout A, Gruenbaum Y, Liu J. Age-related changes of nuclear architecture in Caenorhabditis elegans. Proc Natl Acad Sci USA 2005; 102:16690–16695. doi: 10.1073/pnas.0506955102 16269543
7. Marais GAB, Gaillard J-M, Vieira C, Plotton I, Sanlaville D, Gueyffier F, Lemaitre JF. Sex gap in aging and longevity: can sex chromosomes play a role? Biol Sex Differ. 2018; 9:33–14. doi: 10.1186/s13293-018-0181-y 30016998
8. Wood JG, Jones BC, Jiang N, Chang C, Hosier S, Wickremesinghe P, Garcia M, Hartnett DA, Burhenn L, Neretti N, Helfand SL. Chromatin-modifying genetic interventions suppress age-associated transposable element activation and extend life span in Drosophila. Proc Natl Acad Sci USA. 2016; 113:11277–11282. doi: 10.1073/pnas.1604621113 27621458
9. Wood JG, Hillenmeyer S, Lawrence C, Chang C, Hosier S, Lightfoot W, Mukherjee E, Jiang N, Schorl C, Brodsky AS, Neretti N, Helfand SL. Chromatin remodeling in the aging genome of Drosophila. Aging Cell. 2010; 9:971–978. doi: 10.1111/j.1474-9726.2010.00624.x 20961390
10. De Cecco M, Criscione SW, Peckham EJ, Hillenmeyer S, Hamm EA, Manivannan J, Peterson AL, Kreiling JA, Neretti N, Sedivy JM. Genomes of replicatively senescent cells undergo global epigenetic changes leading to gene silencing and activation of transposable elements. Aging Cell. 2013; 12:247–256. doi: 10.1111/acel.12047 23360310
11. Li W, Prazak L, Chatterjee N, Grüninger S, Krug L, Theodorou D, Dubnau J. Activation of transposable elements during aging and neuronal decline in Drosophila. Nat Neurosci. 2013; 16:529–531. doi: 10.1038/nn.3368 23563579
12. Brown EJ, Nguyen AH, Bachtrog D. The Y chromosome may contribute to sex-specific ageing in Drosophila. Nat Ecol Evol. 2020; 37:466–10.
13. Chang C-H, Larracuente AM. Heterochromatin-Enriched Assemblies Reveal the Sequence and Organization of the Drosophila melanogaster Y Chromosome. Genetics. 2019; 211:333–348. doi: 10.1534/genetics.118.301765 30420487
14. Mahajan S, Wei KH-C, Nalley MJ, Gibilisco L, Bachtrog D. De novo assembly of a young Drosophila Y chromosome using single-molecule sequencing and chromatin conformation capture. PLoS Biol 2018; 16:e2006348. doi: 10.1371/journal.pbio.2006348 30059545
15. Steinemann M, Steinemann S. Degenerating Y chromosome of Drosophila miranda: a trap for retrotransposons. Proc Natl Acad Sci USA. 1992; 89:7591–7595. doi: 10.1073/pnas.89.16.7591 1323846
16. Bachtrog D. Expression profile of a degenerating neo-y chromosome in Drosophila. Curr Biol. 2006; 16:1694–1699. doi: 10.1016/j.cub.2006.07.053 16950105
17. Bachtrog D, Hom E, Wong KM, Maside X, de Jong P. Genomic degradation of a young Y chromosome in Drosophila miranda. Genome Biol. 2008; 9:R30. doi: 10.1186/gb-2008-9-2-r30 18269752
18. Zhou Q, Bachtrog D. Sex-specific adaptation drives early sex chromosome evolution in Drosophila. Science. 2012; 337:341–345. doi: 10.1126/science.1225385 22822149
19. Ellison CE, Bachtrog D. Dosage compensation via transposable element mediated rewiring of a regulatory network. Science. 2013; 342:846–850. doi: 10.1126/science.1239552 24233721
20. Bachtrog D, Charlesworth B. Reduced adaptation of a non-recombining neo-Y chromosome. Nature. 2002; 416:323–326. doi: 10.1038/416323a 11907578
21. Bachtrog D. Accumulation of Spock and Worf, two novel non-LTR retrotransposons, on the neo-Y chromosome of Drosophila miranda. Mol Biol Evol. 2003; 20:173–181. doi: 10.1093/molbev/msg035 12598683
22. Bachtrog D, Mahajan S, Bracewell R. Massive gene amplification on a recently formed Drosophila Y chromosome. Nat Ecol Evol. 2019; 3:1587–1597. doi: 10.1038/s41559-019-1009-9 31666742
23. Zhou Q, Ellison CE, Kaiser VB, Alekseyenko AA, Gorchakov AA, Bachtrog D. The epigenome of evolving Drosophila neo-sex chromosomes: dosage compensation and heterochromatin formation. PLoS Biol. 2013; 11:e1001711. doi: 10.1371/journal.pbio.1001711 24265597
24. Bracewell R, Chatla K, Nalley MJ, Bachtrog D. Dynamic turnover of centromeres drives karyotype evolution in Drosophila. Elife. 2019; 8:923. doi: 10.7554/eLife.49002 31524597
25. Yoon JS, Gagen KP, Zhu DL. Longevity of 68 species of Drosophila. Ohio J Sci. 1990; 90:16–32.
26. Tower J, Arbeitman M. The genetics of gender and life span. J Biol. 2009; 8:38–3. doi: 10.1186/jbiol141 19439039
27. Brenman-Suttner DB, Yost RT, Frame AK, Robinson JW, Moehring AJ, Simon AF. Social behavior and aging: A fly model. Genes Brain Behav. 2020; 19:e12598. doi: 10.1111/gbb.12598 31286644
28. Li X-Y, Harrison MM, Villalta JE, Kaplan T, Eisen MB. Establishment of regions of genomic activity during the Drosophila maternal to zygotic transition. Elife. 2014; 3:e1003428. doi: 10.7554/eLife.03737 25313869
29. Sun L, Yu R, Dang W. Chromatin Architectural Changes during Cellular Senescence and Aging. Genes. 2018; 9:211. doi: 10.3390/genes9040211 29659513
30. Elgin SCR, Reuter G. Position-effect variegation, heterochromatin formation, and gene silencing in Drosophila. Cold Spring Harb Perspect Biol. 2013; 5:a017780–a017780. doi: 10.1101/cshperspect.a017780 23906716
31. Allshire RC, Madhani HD. Ten principles of heterochromatin formation and function. Nat Rev Mol Cell Biol. 2018; 19:229–244. doi: 10.1038/nrm.2017.119 29235574
32. Molaro A, Malik HS. Hide and seek: how chromatin-based pathways silence retroelements in the mammalian germline. Curr Opin Genet Dev. 2016; 37:51–58. doi: 10.1016/j.gde.2015.12.001 26821364
33. Jin Y, Tam OH, Paniagua E, Hammell M. TEtranscripts: a package for including transposable elements in differential expression analysis of RNA-seq datasets. Bioinformatics 2015; 31:3593–3599. doi: 10.1093/bioinformatics/btv422 26206304
34. Kuhn GCS. Satellite DNA transcripts have diverse biological roles in Drosophila. Heredity 2015; 115:1–2. doi: 10.1038/hdy.2015.12 25806543
35. Usakin L, Abad J, Vagin VV, de Pablos B, Villasante A, Gvozdev VA. Transcription of the 1.688 satellite DNA family is under the control of RNA interference machinery in Drosophila melanogaster ovaries. Genetics 2007; 176:1343–1349. doi: 10.1534/genetics.107.071720 17409066
36. Topp CN, Zhong CX, Dawe RK. Centromere-encoded RNAs are integral components of the maize kinetochore. Proc Natl Acad Sci USA. 2004; 101:15986–15991. doi: 10.1073/pnas.0407154101 15514020
37. Mills WK, Lee YCG, Kochendoerfer AM, Dunleavy EM, Karpen GH. RNA from a simple-tandem repeat is required for sperm maturation and male fertility in Drosophila melanogaster. Elife. 2019; 8:229. doi: 10.7554/eLife.48940 31687931
38. Wei KH-C, Lower SE, Caldas IV, Sless TJS, Barbash DA, Clark AG. Variable Rates of Simple Satellite Gains across the Drosophila Phylogeny. Mol Biol Evol. 2018; 35:925–941. doi: 10.1093/molbev/msy005 29361128
39. Riddle NC, Shaffer CD, Elgin SCR. A lot about a little dot—lessons learned from Drosophila melanogaster chromosome 4. Biochem Cell Biol. 2009; 87:229–241. doi: 10.1139/O08-119 19234537
40. Yasuhara JC, DeCrease CH, Wakimoto BT. Evolution of heterochromatic genes of Drosophila. Proc Natl Acad Sci USA. 2005; 102:10958–10963. doi: 10.1073/pnas.0503424102 16033869
41. Yasuhara JC, Wakimoto BT. Molecular landscape of modified histones in Drosophila heterochromatic genes and euchromatin-heterochromatin transition zones. PLoS Genet. 2008; 4:e16. doi: 10.1371/journal.pgen.0040016 18208336
42. Ivics Z, Izsvák Z. Repetitive elements and genome instability. Semin Cancer Biol. 2010; 20:197–199. doi: 10.1016/j.semcancer.2010.08.002 20851335
43. Bourque G, Burns KH, Gehring M, Gorbunova V, Seluanov A, Hammell M, Imbeault M, Izsvák Z, Levin HL, Macfarlan TS, Mager DL, Feschotte C. Ten things you should know about transposable elements. Genome Biol. 2018; 19:199. doi: 10.1186/s13059-018-1577-z 30454069
44. Werren JH. Selfish genetic elements, genetic conflict, and evolutionary innovation. Proc Natl Acad Sci USA 2011; 108 Suppl 2:10863–10870.
45. Hurst GD, Werren JH. The role of selfish genetic elements in eukaryotic evolution. Nat Rev Genet 2001; 2:597–606. doi: 10.1038/35084545 11483984
46. Charlesworth B, Langley CH. The evolution of self-regulated transposition of transposable elements. Genetics 1986; 112:359–383. 3000868
47. Cosby RL, Chang N-C, Feschotte C. Host-transposon interactions: conflict, cooperation, and cooption. Genes Dev. 2019; 33:1098–1116. doi: 10.1101/gad.327312.119 31481535
48. O’Sullivan RJ, Karlseder J. The great unravelling: chromatin as a modulator of the aging process. Trends Biochem Sci. 2012; 37:466–476. doi: 10.1016/j.tibs.2012.08.001 22959736
49. Bousios A, Nützmann H-W, Buck D, Michieletto D. Integrating transposable elements in the 3D genome. Mob DNA. 2020; 11:8–10. doi: 10.1186/s13100-020-0202-3 32042316
50. Charlesworth B, Charlesworth D. The degeneration of Y chromosomes. Philos Trans R Soc Lond, B, Biol Sci. 2000; 355:1563–1572. doi: 10.1098/rstb.2000.0717 11127901
51. Hill WG, Robertson A. The effect of linkage on limits to artificial selection. Genet Res. 1966; 8:269–294. 5980116
52. Bachtrog D Y-chromosome evolution: emerging insights into processes of Y-chromosome degeneration. Nat Rev Genet. 2013; 14:113–124. doi: 10.1038/nrg3366 23329112
53. Pimpinelli S, Berloco M, Fanti L, Dimitri P, Bonaccorsi S, Marchetti E, Caizzi R, Caggese C, Gatti M. Transposable elements are stable structural components of Drosophila melanogaster heterochromatin. Proc Natl Acad Sci USA. 1995; 92:3804–3808. doi: 10.1073/pnas.92.9.3804 7731987
54. Gatti M, Pimpinelli S. Functional elements in Drosophila melanogaster heterochromatin. Annu Rev Genet. 1992; 26:239–275. doi: 10.1146/annurev.ge.26.120192.001323 1482113
55. Wei KH-C, Gibilisco L, Bachtrog D. Epigenetic conflict on a degenerating Y chromosome increases mutational burden in Drosophila males. Nat Commun. 2020;11: 5537–9. doi: 10.1038/s41467-020-19134-9 33139741
56. Frost B, Hemberg M, Lewis J, Feany MB. Tau promotes neurodegeneration through global chromatin relaxation. Nat Neurosci. 2014;17: 357–366. doi: 10.1038/nn.3639 24464041
57. Van Meter M, Kashyap M, Rezazadeh S, Geneva AJ, Morello TD, Seluanov A, Gorbunova V. SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age. Nat Commun. 2014;5: 5011–10. doi: 10.1038/ncomms6011 25247314
58. De Cecco M, Ito T, Petrashen AP, Elias AE, Skvir NJ, Criscione SW, et al. L1 drives IFN in senescent cells and promotes age-associated inflammation. Nature. 2019;566: 73–78. doi: 10.1038/s41586-018-0784-9 30728521
59. Chen H, Zheng X, Zheng Y. Age-associated loss of lamin-B leads to systemic inflammation and gut hyperplasia. Cell. 2014;159: 829–843. doi: 10.1016/j.cell.2014.10.028 25417159
60. Brind’Amour J, Liu S, Hudson M, Chen C, Karimi MM, Lorincz MC. An ultra-low-input native ChIP-seq protocol for genome-wide profiling of rare cell populations. Nat Commun. 2015; 6:6033. doi: 10.1038/ncomms7033 25607992
61. Hoskins RA, Carlson JW, Wan KH, Park S, Mendez I, Galle SE, et al. The Release 6 reference sequence of the Drosophila melanogaster genome. Genome Res. 2015; 25:445–458. doi: 10.1101/gr.185579.114 25589440
62. Langmead B, Salzberg SL. Fast gapped-read alignment with Bowtie 2. Nat Methods. 2012; 9:357–359. doi: 10.1038/nmeth.1923 22388286
63. Brown EJ, Nguyen AH, Bachtrog D. The Drosophila Y chromosome affects heterochromatin integrity genome-wide. Mol. Biol. Evol. 2020; 37: 2808–2824. doi: 10.1093/molbev/msaa082 32211857
64. Quinlan AR, Hall IM. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics. 2010; 26:841–842. doi: 10.1093/bioinformatics/btq033 20110278
65. Bonhoure N, Bounova G, Bernasconi D, Praz V, Lammers F, Canella D, Willis IM, Herr W, Hernandez N, Delorenzi M. Quantifying ChIP-seq data: a spiking method providing an internal reference for sample-to-sample normalization. Genome Res. 2014; 24:1157–1168. doi: 10.1101/gr.168260.113 24709819
66. Kim D, Langmead B, Salzberg SL. HISAT: a fast spliced aligner with low memory requirements. Nat Methods. 2015; 12:357–360. doi: 10.1038/nmeth.3317 25751142
67. Liao Y, Smyth GK, Shi W. featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics. 2014; 30:923–930. doi: 10.1093/bioinformatics/btt656 24227677
68. Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014; 15:550–21. doi: 10.1186/s13059-014-0550-8 25516281
69. Goubert C, Modolo L, Vieira C, ValienteMoro C, Mavingui P, Boulesteix M. De novo assembly and annotation of the Asian tiger mosquito (Aedes albopictus) repeatome with dnaPipeTE from raw genomic reads and comparative analysis with the yellow fever mosquito (Aedes aegypti). Genome Biol Evol. 2015; 7: 1192–1205. doi: 10.1093/gbe/evv050 25767248
70. Hill T, Betancourt AJ. Extensive exchange of transposable elements in the Drosophila pseudoobscura group. Mob DNA 2018; 9:20. doi: 10.1186/s13100-018-0123-6 29946370
71. Fanti L, Perrini B, Piacentini L, Berloco M, Marchetti E, Palumbo G, et al. The trithorax group and Pc group proteins are differentially involved in heterochromatin formation in Drosophila. Chromosoma. 2008; Springer-Verlag;;117: 25–39. doi: 10.1007/s00412-007-0123-7 17823810
72. Kaplan EL, Meier P. Nonparametric Estimation from Incomplete Observations. Journal of the American Statistical Association. 1958; 53:457–481.
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