Carefully maintained and precisely inherited chromosomal DNA provides long-term genetic stability, but eukaryotic cells facing environmental challenges can benefit from the accumulation of less stable DNA species. Circular DNA molecules lacking centromeres segregate randomly or asymmetrically during cell division, following non-Mendelian inheritance patterns that result in high copy number instability and massive heterogeneity across populations. Such circular DNA species, variously known as extrachromosomal circular DNA (eccDNA), microDNA, double minutes or extrachromosomal DNA (ecDNA), are becoming recognised as a major source of the genetic variation exploited by cancer cells and pathogenic eukaryotes to acquire drug resistance. In budding yeast, circular DNA molecules derived from the ribosomal DNA (ERCs) have been long known to accumulate with age, but it is now clear that aged yeast also accumulate other high-copy protein-coding circular DNAs acquired through both random and environmentally-stimulated recombination processes. Here, we argue that accumulation of circular DNA provides a reservoir of heterogeneous genetic material that can allow rapid adaptation of aged cells to environmental insults, but avoids the negative fitness impacts on normal growth of unsolicited gene amplification in the young population.

中文翻译：

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衰老细胞中环状DNA积累的适应潜力。

精心维护并精确遗传的染色体DNA可提供长期的遗传稳定性，但是面临环境挑战的真核细胞可受益于不稳定的DNA种类的积累。缺乏着丝粒的环状DNA分子在细胞分裂过程中随机或不对称地分离，遵循非孟德尔遗传模式，导致种群间高拷贝数不稳定和大量异质性。这类环状DNA种类，也称为染色体外环状DNA（eccDNA），微小DNA，双分钟或染色体外DNA（ecDNA），已被公认为是癌细胞和致病性真核生物利用遗传变异获得耐药性的主要来源。在发芽酵母中 众所周知，随着年龄的增长，源自核糖体DNA（ERC）的环状DNA分子会积累，但现在很清楚，老化的酵母还会积累通过随机和环境刺激的重组过程获得的其他高拷贝蛋白质编码环状DNA。在这里，我们认为环状DNA的积累提​​供了异质遗传物质的储备，可以使衰老的细胞快速适应环境的侵害，但避免了对年轻人群中不请自来的基因扩增的正常生长的不利适应性影响。