The y chromosome may contribute to sex-specific ageing in drosophila

ABSTRACT Heterochromatin suppresses repetitive DNA, and a loss of heterochromatin has been observed in aged cells of several species, including humans and _Drosophila_. Males often contain

substantially more heterochromatic DNA than females, due to the presence of a large, repeat-rich Y chromosome, and male flies generally have a shorter average lifespan than females. Here we

show that repetitive DNA becomes de-repressed more rapidly in old male flies relative to females, and repeats on the Y chromosome are disproportionally mis-expressed during ageing. This is

associated with a loss of heterochromatin at repetitive elements during ageing in male flies, and a general loss of repressive chromatin in aged males away from pericentromeric regions and

the Y. By generating flies with different sex chromosome karyotypes (XXY females and X0 and XYY males), we show that repeat de-repression and average lifespan is correlated with the number

of Y chromosomes. This suggests that sex-specific chromatin differences may contribute to sex-specific ageing in flies. Access through your institution Buy or subscribe This is a preview of

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TO SEX-SPECIFIC DIFFERENCES IN LONGEVITY Article Open access 12 June 2023 EPIGENETIC CONFLICT ON A DEGENERATING Y CHROMOSOME INCREASES MUTATIONAL BURDEN IN DROSOPHILA MALES Article Open

access 02 November 2020 TRANSCRIPTIONAL AND MUTATIONAL SIGNATURES OF THE _DROSOPHILA_ AGEING GERMLINE Article 12 January 2023 DATA AVAILABILITY All RNA-seq and ChIP–seq reads are deposited

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Assoc._ 53, 457–481 (1958). Article  Google Scholar  Download references ACKNOWLEDGEMENTS D.B. was funded by NIH grants (nos. R01GM076007, GM101255 and R01AG057029). AUTHOR INFORMATION

AUTHORS AND AFFILIATIONS * Department of Integrative Biology, University of California Berkeley, Berkeley, CA, USA Emily J. Brown, Alison H. Nguyen & Doris Bachtrog Authors * Emily J.

Brown View author publications You can also search for this author inPubMed Google Scholar * Alison H. Nguyen View author publications You can also search for this author inPubMed Google

Scholar * Doris Bachtrog View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS D.B. and E.J.B. conceived the study and wrote the paper. E.J.B.

and A.H.N. collected and analysed the data. CORRESPONDING AUTHOR Correspondence to Doris Bachtrog. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing interests.

ADDITIONAL INFORMATION PUBLISHER’S NOTE Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EXTENDED DATA EXTENDED DATA

FIG. 1 SURVIVORSHIP CURVES OF ADDITIONAL _D. MELANOGASTER_ STRAINS. Shown are Kaplan-Meier survivorship curves for line 2549 males and females ((C(1;Y),y1cv1v1B/0 & C(1)RM,y1v1/0) and

Oregon-R wild-type males and females. EXTENDED DATA FIG. 2 GENOME-WIDE ENRICHMENT OF H3K9ME2 FOR REPLICATE YOUNG AND OLD _D. MELANOGASTER_ MALES AND FEMALES ALONG THE DIFFERENT CHROMOSOME

ARMS. Pearson correlation coefficients for replicate H3K9me2 datasets for old males and females, and boxplots of normalized enrichment values for the replicates. Genome-wide plots were

generated using biological replicate data as in Fig. 1b,d. EXTENDED DATA FIG. 3 LOSS AND GAIN OF HETEROCHROMATIN DURING AGEING. Shown are chromosomal locations of 50 kb windows that gain

(red) or lose (blue) at least 1.5-fold H3K9me2 signal during ageing for males and females. Pericentromeric regions are indicated by the red portion of the line beneath each chromosome.

SUPPLEMENTARY INFORMATION SUPPLEMENTARY INFORMATION Supplementary Figs. 1–19 and Tables 1 and 2. REPORTING SUMMARY SUPPLEMENTARY TABLE 3 AND 4 Gene expression changes during ageing in (A) XX

females, (B) XY males, (C) X0 males, (D) XXY females and (E) XYY males. Enriched GO categories of genes that significantly changed expression during ageing in (A) XX females, (B) XY males,

(C) X0 males, (D) XXY females and (E) XYY males. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Brown, E.J., Nguyen, A.H. & Bachtrog, D. The Y

chromosome may contribute to sex-specific ageing in _Drosophila_. _Nat Ecol Evol_ 4, 853–862 (2020). https://doi.org/10.1038/s41559-020-1179-5 Download citation * Received: 16 September 2019

* Accepted: 16 March 2020 * Published: 20 April 2020 * Issue Date: June 2020 * DOI: https://doi.org/10.1038/s41559-020-1179-5 SHARE THIS ARTICLE Anyone you share the following link with

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