Selective benefits of damage partitioning in unicellular systems and its effects on aging
Selective benefits of damage partitioning in unicellular systems and its effects on aging
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DOI：
10.1073/pnas.0804550105
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发表时间：
2008-12-02
影响因子：
11.1
通讯作者：
Nystrom, T.
中科院分区：
文献类型：
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作者：
Erjavec, N.;Cvijovic, M.;Nystrom, T.
单细胞生物的细胞质分裂有时需要细胞之间的分工，导致谱系特异性衰老。为了研究不对称细胞分裂的潜在好处，我们创建了一个数学模型来模拟具有不同程度损伤分离和大小不对称的分裂系统的鲁棒性和适应度。该模型表明，不对称分裂（大小方向）或显示损伤分离的系统可以在进入克隆衰老之前承受更高程度的损伤。当考虑种群适应度时，一个产生不同大小后代的系统，如出芽酵母，预计只有在高伤害繁殖率下才能从伤害保留中受益。相比之下，无论损伤传播速率如何，具有相同大小后代的系统的适应性都可以通过损伤分离得到增强，这表明损伤分离可能也为二元裂变分裂的系统提供了进化优势。事实上，通过使用裂糖酵母作为模型，我们实验证明在细胞质分裂过程中受损的蛋白质是不均匀分裂的，并且受损的兄弟姐妹遭受了较长的世代时间和加速老化。与酿酒酵母一样，S. pombe中的这种损伤保留依赖于Sir2p和细胞骨架，这表明这是一种进化保守的机制。我们认为，兄弟姐妹特异性老化可能是损伤分离的强选择优势的结果，这可能在自然界中比以前预期的更常见。
Cytokinesis in unicellular organisms sometimes entails a division of labor between cells leading to lineage-specific aging. To investigate the potential benefits of asymmetrical cytokinesis, we created a mathematical model to simulate the robustness and fitness of dividing systems displaying different degrees of damage segregation and size asymmetries. The model suggests that systems dividing asymmetrically (size-wise) or displaying damage segregation can withstand higher degrees of damage before entering clonal senescence. When considering population fitness, a system producing different-sized progeny like budding yeast is predicted to benefit from damage retention only at high damage propagation rates. In contrast, the fitness of a system of equal-sized progeny is enhanced by damage segregation regardless of damage propagation rates, suggesting that damage partitioning may also provide an evolutionary advantage in systems dividing by binary fission. Indeed, by using Schizosaccharomyces pombe as a model, we experimentally demonstrate that damaged proteins are unevenly partitioned during cytokinesis and the damage-enriched sibling suffers from a prolonged generation time and accelerated aging. This damage retention in S. pombe is, like in Saccharomyces cerevisiae, Sir2p- and cytoskeleton-dependent, suggesting this to be an evolutionarily conserved mechanism. We suggest that sibling-specific aging may be a result of the strong selective advantage of damage segregation, which may be more common in nature than previously anticipated.