Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, MI, USA.
Nat Commun. 2021 Jun 30;12(1):4044. doi: 10.1038/s41467-021-24364-6.
What determines the rate (μ) and molecular spectrum of mutation is a fundamental question. The prevailing hypothesis asserts that natural selection against deleterious mutations has pushed μ to the minimum achievable in the presence of genetic drift, or the drift barrier. Here we show that, contrasting this hypothesis, μ substantially exceeds the drift barrier in diverse organisms. Random mutation accumulation (MA) in yeast frequently reduces μ, and deleting the newly discovered mutator gene PSP2 nearly halves μ. These results, along with a comparison between the MA and natural yeast strains, demonstrate that μ is maintained above the drift barrier by stabilizing selection. Similar comparisons show that the mutation spectrum such as the universal AT mutational bias is not intrinsic but has been selectively preserved. These findings blur the separation of mutation from selection as distinct evolutionary forces but open the door to alleviating mutagenesis in various organisms by genome editing.
是什么决定了突变的速率(μ)和分子谱是一个基本问题。流行的假说认为,对有害突变的自然选择将μ推到了遗传漂变或漂变屏障下可达到的最小值。在这里,我们表明,与这一假说相反,μ在多种生物中大大超过了漂变屏障。酵母中的随机突变积累(MA)经常降低μ,而删除新发现的诱变基因 PSP2 几乎将 μ 减半。这些结果,以及 MA 和天然酵母菌株之间的比较,表明稳定选择将 μ维持在漂变屏障之上。类似的比较表明,突变谱,如普遍的 AT 突变偏向,不是内在的,而是被选择性地保留下来的。这些发现模糊了突变与选择作为不同进化力量的分离,但为通过基因组编辑减轻各种生物体中的诱变开辟了道路。