Department of Integrative Biology, University of California Berkeley, Berkeley, CA, USA.
Nat Ecol Evol. 2020 Jun;4(6):853-862. doi: 10.1038/s41559-020-1179-5. Epub 2020 Apr 20.
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.
异染色质抑制重复 DNA,在包括人类和果蝇在内的几种物种的衰老细胞中,已经观察到异染色质的丢失。由于存在一个大的、富含重复序列的 Y 染色体,雄性通常比雌性含有更多的异染色质 DNA,而雄性苍蝇的平均寿命通常比雌性短。在这里,我们发现与雌性相比,雄性衰老过程中重复 DNA 的去抑制速度更快,并且 Y 染色体上的重复序列在衰老过程中不成比例地错误表达。这与雄性苍蝇衰老过程中重复元件的异染色质丢失以及远离着丝粒区域和 Y 的老年雄性中一般抑制染色质的丢失有关。通过产生具有不同性染色体核型的苍蝇(XXY 雌性和 X0 和 XYY 雄性),我们发现重复序列的去抑制和平均寿命与 Y 染色体的数量相关。这表明性别特异性染色质差异可能导致苍蝇的性别特异性衰老。