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Mutability of mononucleotide repeats, not oxidative stress, explains the discrepancy between laboratory-accumulated mutations and the natural allele-frequency spectrum in C. elegans
Genome Research ( IF 6.2 ) Pub Date : 2021-09-01 , DOI: 10.1101/gr.275372.121
Moein Rajaei 1 , Ayush Shekhar Saxena 1 , Lindsay M Johnson 1 , Michael C Snyder 1 , Timothy A Crombie 1, 2 , Robyn E Tanny 2 , Erik C Andersen 2 , Joanna Joyner-Matos 3 , Charles F Baer 1, 4
Affiliation  

Important clues about natural selection can be gleaned from discrepancies between the properties of segregating genetic variants and of mutations accumulated experimentally under minimal selection, provided the mutational process is the same in the laboratory as in nature. The base-substitution spectrum differs between C. elegans laboratory mutation accumulation (MA) experiments and the standing site-frequency spectrum, which has been argued to be in part owing to increased oxidative stress in the laboratory environment. Using genome sequence data from C. elegans MA lines carrying a mutation (mev-1) that increases the cellular titer of reactive oxygen species (ROS), leading to increased oxidative stress, we find the base-substitution spectrum is similar between mev-1, its wild-type progenitor (N2), and another set of MA lines derived from a different wild strain (PB306). Conversely, the rate of short insertions is greater in mev-1, consistent with studies in other organisms in which environmental stress increased the rate of insertion–deletion mutations. Further, the mutational properties of mononucleotide repeats in all strains are different from those of nonmononucleotide sequence, both for indels and base-substitutions, and whereas the nonmononucleotide spectra are fairly similar between MA lines and wild isolates, the mononucleotide spectra are very different, with a greater frequency of A:T → T:A transversions and an increased proportion of ±1-bp indels. The discrepancy in mutational spectra between laboratory MA experiments and natural variation is likely owing to a consistent (but unknown) effect of the laboratory environment that manifests itself via different modes of mutability and/or repair at mononucleotide loci.

中文翻译:

单核苷酸重复的可变性,而不是氧化应激,解释了实验室积累的突变与秀丽隐杆线虫的自然等位基因频谱之间的差异

关于自然选择的重要线索可以从分离遗传变异的性质和在最小选择下实验积累的突变之间的差异中收集,前提是实验室中的突变过程与自然界中的突变过程相同。秀丽隐杆线虫实验室突变积累 (MA) 实验和常设位点频谱之间的碱基取代谱不同,这被认为部分是由于实验室环境中氧化应激的增加。使用来自携带突变 ( mev - 1 ) 的秀丽隐杆线虫MA 系的基因组序列数据) 增加活性氧 (ROS) 的细胞滴度,导致氧化应激增加,我们发现mev - 1、其野生型祖细胞 (N2) 和另一组衍生的 MA 系之间的碱基取代谱相似来自不同的野生菌株(PB306)。相反,短插入率在mev - 1中更大,与其他生物体的研究一致,在这些生物体中,环境压力会增加插入-缺失突变率。此外,所有菌株中单核苷酸重复序列的突变特性与非单核苷酸序列的突变特性不同,无论是插入缺失还是碱基替换,虽然 MA 系和野生分离株之间的非单核苷酸谱非常相似,但单核苷酸谱却非常不同,与A:T → T:A 颠换的频率更高,±1-bp 插入缺失的比例增加。实验室 MA 实验和自然变异之间突变谱的差异可能是由于实验室环境的一致(但未知)影响,其通过不同模式的可变性和/或单核苷酸位点的修复表现出来。
更新日期:2021-09-01
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