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复制性衰老与酿酒酵母中外源环状 DNA 遗传异质性的丧失有关。

Replicative aging is associated with loss of genetic heterogeneity from extrachromosomal circular DNA in Saccharomyces cerevisiae.

机构信息

Ecology and Evolution, Department of Biology, University of Copenhagen, Copenhagen DK-2100, Denmark.

Department of Biology, Institute of Biochemistry, ETH Zürich, Zurich CH-8093, Switzerland.

出版信息

Nucleic Acids Res. 2020 Aug 20;48(14):7883-7898. doi: 10.1093/nar/gkaa545.

DOI:10.1093/nar/gkaa545
PMID:32609810
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7430651/
Abstract

Circular DNA can arise from all parts of eukaryotic chromosomes. In yeast, circular ribosomal DNA (rDNA) accumulates dramatically as cells age, however little is known about the accumulation of other chromosome-derived circles or the contribution of such circles to genetic variation in aged cells. We profiled circular DNA in Saccharomyces cerevisiae populations sampled when young and after extensive aging. Young cells possessed highly diverse circular DNA populations but 94% of the circular DNA were lost after ∼15 divisions, whereas rDNA circles underwent massive accumulation to >95% of circular DNA. Circles present in both young and old cells were characterized by replication origins including circles from unique regions of the genome and repetitive regions: rDNA and telomeric Y' regions. We further observed that circles can have flexible inheritance patterns: [HXT6/7circle] normally segregates to mother cells but in low glucose is present in up to 50% of cells, the majority of which must have inherited this circle from their mother. Interestingly, [HXT6/7circle] cells are eventually replaced by cells carrying stable chromosomal HXT6 HXT6/7 HXT7 amplifications, suggesting circular DNAs are intermediates in chromosomal amplifications. In conclusion, the heterogeneity of circular DNA offers flexibility in adaptation, but this heterogeneity is remarkably diminished with age.

摘要

环状 DNA 可以从真核染色体的所有部位产生。在酵母中，环状核糖体 DNA（rDNA）随着细胞衰老而大量积累，但对于其他源自染色体的环状 DNA 的积累或这些环状 DNA 对衰老细胞遗传变异的贡献知之甚少。我们对处于年轻状态和广泛衰老后的酿酒酵母群体中的环状 DNA 进行了分析。年轻细胞具有高度多样化的环状 DNA 群体，但在大约 15 次分裂后，有 94%的环状 DNA 丢失，而 rDNA 环则大量积累到超过 95%的环状 DNA。在年轻和年老细胞中都存在的环的特征是复制起点，包括来自基因组独特区域和重复区域的环：rDNA 和端粒 Y'区域。我们进一步观察到，环可以具有灵活的遗传模式：[HXT6/7circle]通常分配给母细胞，但在低葡萄糖条件下，多达 50%的细胞中存在[HXT6/7circle]，其中大多数细胞必须从其母细胞继承这个环。有趣的是，[HXT6/7circle]细胞最终被携带稳定染色体 HXT6 HXT6/7 HXT7 扩增的细胞所取代，这表明环状 DNA 是染色体扩增的中间产物。总之，环状 DNA 的异质性为适应提供了灵活性，但这种异质性随着年龄的增长而显著降低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bdb/7430651/d1f5ff81caab/gkaa545fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bdb/7430651/ae4b20a55fb3/gkaa545fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bdb/7430651/ec84f38a38d4/gkaa545fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bdb/7430651/42ddbfe20b46/gkaa545fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bdb/7430651/ec3788ef2774/gkaa545fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bdb/7430651/d2d2e3690a16/gkaa545fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bdb/7430651/744728837ffa/gkaa545fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bdb/7430651/d1f5ff81caab/gkaa545fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bdb/7430651/ae4b20a55fb3/gkaa545fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bdb/7430651/ec84f38a38d4/gkaa545fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bdb/7430651/42ddbfe20b46/gkaa545fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bdb/7430651/ec3788ef2774/gkaa545fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bdb/7430651/d2d2e3690a16/gkaa545fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bdb/7430651/744728837ffa/gkaa545fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bdb/7430651/d1f5ff81caab/gkaa545fig7.jpg

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