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.
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All RNA-seq and ChIP–seq reads are deposited at NCBI under BioProject ID PRJNA594556.
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D.B. was funded by NIH grants (nos. R01GM076007, GM101255 and R01AG057029).
The authors declare no competing interests.
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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.
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 Figs. 1–19 and Tables 1 and 2.
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.
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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
Trends in Genetics (2020)