Selective benefits of damage partitioning in unicellular systems and its effects on aging

• Published in: Proceedings of the National Academy of Sciences - PNAS 2008-12, Vol.105 (48), p.18764-18769
• Main Authors: Erjavec, N, Cvijovic, M, Klipp, E, Nyström, T
• Format: Article
• Language: English
• Subjects: Aging; Animals; Asymmetry; Biological Sciences; Cell cycle; cell polarity; Cell separation; Cells; Cellular senescence; Cellular Senescence - physiology; Cytokines; Cytokinesis; Cytokinesis - physiology; Cytoskeleton; Daughter cells; Division of labor; Evolution; fibroblasts; fission yeast; Fitness; Germ cells; growth; life-span; Mathematical models; Models, Theoretical; Mother cells; Progenitor cells; Progeny; proteins; Saccharomyces cerevisiae; Schizosaccharomyces - cytology; Schizosaccharomyces - physiology; Schizosaccharomyces pombe; Schizosaccharomyces pombe Proteins - genetics; Schizosaccharomyces pombe Proteins - metabolism; segregation; Senescence; Siblings; Social Sciences Interdisciplinary; Tvärvetenskapliga studier; Yeast; yeast schizosaccharomyces-pombe; Yeasts
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.0804550105

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.