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生殖系基因组——生物的青春源泉?

Germline genomes--a biological fountain of youth?

作者信息

Walter Christi A, Walter Ronald B, McCarrey John R

机构信息

The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA.

出版信息

Sci Aging Knowledge Environ. 2003 Feb 26;2003(8):PE4. doi: 10.1126/sageke.2003.8.pe4.

Abstract

The fusion of male- and female-derived gametes initiates the phenomenal process of producing a highly complex mammalian organism. Successful reproduction is so important that mammals invoke a battery of protective mechanisms for the germ cell lineages that function to maximize genetic integrity while still allowing genetic diversity and adaptation. Protective mechanisms likely include, but are not limited to, robust DNA repair to safeguard genetic integrity and apoptosis to remove cells with intolerable levels of DNA damage. Analyses of spontaneous mutant frequencies are generally consistent with germline DNA being stringently maintained relative to somatic tissues. Despite the rigorous protection afforded germ cells, genetic integrity is observed to decline with increased maternal and paternal age. It is not yet clear whether cells in the germ line truly age or whether other processes decline or become dysfunctional with age. For example, in a younger animal, the differentiation and/or utilization of germ cells with lower genetic integrity might be disallowed, whereas in an older animal, such cells might slip past these quality-control mechanisms.

摘要

雄源和雌源配子的融合启动了产生高度复杂哺乳动物有机体这一非凡过程。成功繁殖至关重要,以至于哺乳动物为生殖细胞谱系调用了一系列保护机制,这些机制的作用是在最大化遗传完整性的同时仍允许遗传多样性和适应性。保护机制可能包括但不限于强大的DNA修复以维护遗传完整性,以及细胞凋亡以清除具有无法忍受水平DNA损伤的细胞。自发突变频率的分析总体上与生殖系DNA相对于体细胞组织被严格维持一致。尽管生殖细胞受到了严格保护,但随着母本和父本年龄的增加,遗传完整性仍会下降。目前尚不清楚生殖系中的细胞是否真的会衰老,或者是否其他过程会随着年龄增长而衰退或功能失调。例如,在较年轻的动物中,可能不允许具有较低遗传完整性的生殖细胞进行分化和/或利用,而在较年长的动物中,此类细胞可能会逃过这些质量控制机制。

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