Life Sciences Institute, University of Michigan, Ann Arbor, United States.
Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, United States.
Elife. 2018 Feb 13;7:e32421. doi: 10.7554/eLife.32421.
rDNA loci, composed of hundreds of tandemly duplicated arrays of rRNA genes, are known to be among the most unstable genetic elements due to their repetitive nature. rDNA instability underlies aging (replicative senescence) in yeast cells, however, its contribution to the aging of multicellular organisms is poorly understood. In this study, we investigate the dynamics of rDNA loci during aging in the male germline stem cell (GSC) lineage, and show that rDNA copy number decreases during aging. Our study further reveals that this age-dependent decrease in rDNA copy number is heritable from generation to generation, yet GSCs in young animals that inherited reduced rDNA copy number are capable of recovering normal rDNA copy number. Based on these findings, we propose that rDNA loci are dynamic genetic elements, where rDNA copy number changes dynamically yet is maintained through a recovery mechanism in the germline.
rDNA 基因座由数百个串联重复的 rRNA 基因组成,由于其重复性质,已知是最不稳定的遗传元件之一。rDNA 的不稳定性是酵母细胞衰老(复制性衰老)的基础,然而,其对多细胞生物衰老的贡献尚不清楚。在这项研究中,我们研究了雄性生殖干细胞(GSC)谱系中 rDNA 基因座在衰老过程中的动态变化,并表明 rDNA 拷贝数随着衰老而减少。我们的研究进一步表明,这种 rDNA 拷贝数随年龄的下降是可以遗传的,但从一代到下一代,遗传了 rDNA 拷贝数减少的年轻动物的 GSCs 能够恢复正常的 rDNA 拷贝数。基于这些发现,我们提出 rDNA 基因座是动态遗传元件,rDNA 拷贝数随时间动态变化,但通过生殖系中的恢复机制得以维持。