The rate and molecular spectrum of mutation are selectively maintained in yeast.

The rate and molecular spectrum of mutation are selectively maintained in yeast.
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DOI:
10.1038/s41467-021-24364-6
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发表时间:
2021-06-30
影响因子:
16.6
通讯作者:
Zhang J
Zhang J
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Liu H;Zhang J

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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,针对有害突变的自然选择已经将μ推到了存在遗传漂变或漂变障碍时可达到的最小值。在这里,我们表明,与这一假设相反,μ在不同的生物体中大大超过了漂移障碍。酵母中的随机突变积累(MA)经常会降低μ,而删除新发现的增变基因PSP2几乎会使μ减半。这些结果,沿着MA和天然酵母菌株之间的比较,证明μ通过稳定选择保持在漂移屏障之上。类似的比较表明,突变谱,如通用AT突变的偏见是不是内在的,但已被选择性地保存。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的诱变打开了大门。自然选择如何塑造突变的速率和分子谱是有争议的。酵母突变积累实验鉴定了促进诱变的基因,并显示稳定选择将突变率维持在漂移屏障以上。选择也保留了突变谱。
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. How natural selection shapes the rate and molecular spectrum of mutations is debated. Yeast mutation accumulation experiments identify a gene promoting mutagenesis and show stabilizing selection maintaining the mutation rate above the drift barrier. Selection also preserves the mutation spectrum.
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