Institute of Integrative Biology, ETH Zurich, Zurich, Switzerland.
Swiss Institute of Bioinformatics, Lausanne, Switzerland.
Mol Biol Evol. 2023 Aug 3;40(8). doi: 10.1093/molbev/msad179.
The notion that mutations are random relative to their fitness effects is central to the Neo-Darwinian view of evolution. However, a recent interpretation of the patterns of mutation accumulation in the genome of Arabidopsis thaliana has challenged this notion, arguing for the presence of a targeted DNA repair mechanism that causes a nonrandom association of mutation rates and fitness effects. Specifically, this mechanism was suggested to cause a reduction in the rates of mutations on essential genes, thus lowering the rates of deleterious mutations. Central to this argument were attempts to rule out selection at the population level. Here, we offer an alternative and parsimonious interpretation of the patterns of mutation accumulation previously attributed to mutation bias, showing how they can instead or additionally be caused by developmental selection, that is selection occurring at the cellular level during the development of a multicellular organism. Thus, the depletion of deleterious mutations in A. thaliana may indeed be the result of a selective process, rather than a bias in mutation. More broadly, our work highlights the importance of considering development in the interpretation of population-genetic analyses of multicellular organisms, and it emphasizes that efforts to identify mechanisms involved in mutational biases should explicitly account for developmental selection.
突变相对于其适应度效应的随机性是新达尔文主义进化观的核心。然而，最近对拟南芥基因组中突变积累模式的解释挑战了这一观点，认为存在一种靶向 DNA 修复机制，导致突变率和适应度效应之间存在非随机关联。具体来说，该机制被认为导致必需基因上突变率降低，从而降低有害突变的速率。该论点的核心是试图排除群体水平的选择。在这里，我们对以前归因于突变偏向的突变积累模式提出了另一种简单的解释，展示了它们如何可以替代或另外由发育选择引起，即在多细胞生物发育过程中发生在细胞水平的选择。因此，拟南芥中有害突变的耗尽确实可能是选择过程的结果，而不是突变偏向的结果。更广泛地说，我们的工作强调了在解释多细胞生物的群体遗传学分析时考虑发育的重要性，并且强调了识别突变偏向相关机制的努力应明确考虑发育选择。
