The Cellular, Developmental and Population-Genetic Determinants of Mutation-Rate Evolution
The Cellular, Developmental and Population-Genetic Determinants of Mutation-Rate Evolution
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DOI：
10.1534/genetics.108.090456
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发表时间：
2008-10-01
期刊：
影响因子：
3.3
通讯作者：
Lynch, Michael
中科院分区：
文献类型：
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作者：
Lynch, Michael
虽然这个问题已经受到相当多的理论研究，但关于驱动不同系统发育谱系突变率的机制仍有许多悬而未决的问题。最值得注意的是，经验证据表明，多细胞物种的突变率高于单细胞真核生物和原核生物，即使是在每细胞分裂的基础上，尽管需要避免体细胞损伤和种系突变的积累。本文认为，由于细胞和群体遗传环境相关的原因，多细胞性阻碍了对弱突变等位基因的选择，从而放大了对体细胞突变（癌症）的脆弱性，并增加了因种系突变积累而灭绝的风险。此外，与普遍看法相反，不需要用保真成本来解释观察到的突变率的下限，而可能仅仅是由于在有限的种群中，选择无法推进非常弱的有利的抗突变等位基因。
Although the matter has been subject to considerable theoretical study, there are numerous open questions regarding the mechanisms driving the mutation rate in various phylogenetic lineages. Most notably, empirical evidence indicates that mutation rates are elevated in multicellular species relative to unicellular eukaryotes and prokaryotes, even on a per-cell division basis, despite the need for the avoidance of somatic damage and the accumulation of germline mutations. Here it is Suggested that multicellularity discourages selection against weak mutator alleles for reasons associated with both the cellular and the population-genetic environments, thereby magnifying the vulnerability to somatic Mutations (cancer) and increasing the risk of extinction from the accumulation of germline mutations. Moreover, contrary to common belief, a cost of fidelity need not be invoked to explain the lower bound to observed mutation rates, which instead may simply be set by the inability of selection to advance very weakly advantageous antimutator alleles in finite populations.