Redundancy, antiredundancy, and the robustness of genomes
Redundancy, antiredundancy, and the robustness of genomes
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DOI：
10.1073/pnas.032668599
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发表时间：
2002-02-05
影响因子：
11.1
通讯作者：
Plotkin, JB
中科院分区：
文献类型：
--
作者：
Krakauer, DC;Plotkin, JB
导致表型不可检测或微小变化的基因突变被认为揭示了多余的功能。冗余在经历低突变率和小种群规模的高等生物的表型中很常见。在高突变率和大种群的生物体中，或在多细胞生物体中快速分裂的细胞中，冗余不太常见。在这些情况下，人们甚至观察到相反的趋势：对突变高度敏感，我们称之为反冗余。本文分析了冗余和反冗余的演化动力学。假设冗余的代价，我们发现大种群将进化出消除突变的反冗余机制，从而增强野生型基因组的稳健性；而小种群将进化冗余，以确保所有个体都有很高的生存机会。我们认为，反冗余对于发育的稳健性和冗余一样重要，是确保复杂多细胞生物体组织水平稳定性的基本机制。我们认为，在癌症、线粒体疾病和病毒感染方面，反冗余值得更多地关注。
Genetic mutations that lead to undetectable or minimal changes in phenotypes are said to reveal redundant functions. Redundancy is common among phenotypes of higher organisms that experience low mutation rates and small population sizes. Redundancy is less common among organisms with high mutation rates and large populations, or among the rapidly dividing cells of multicellular organisms. In these cases, one even observes the opposite tendency: a hypersensitivity to mutation, which we refer to as antiredundancy. In this paper we analyze the evolutionary dynamics of redundancy and antiredundancy. Assuming a cost of redundancy, we find that large populations will evolve antiredundant mechanisms for removing mutants and thereby bolster the robustness of wild-type genomes; whereas small populations will evolve redundancy to ensure that all individuals have a high chance of survival. We propose that antiredundancy is as important for developmental robustness as redundancy, and is an essential mechanism for ensuring tissue-level stability in complex multicellular organisms. We suggest that antiredundancy deserves greater attention in relation to cancer, mitochondrial disease, and virus infection.