Inferring the distribution of fitness effects of spontaneous mutations in Chlamydomonas reinhardtii
Inferring the distribution of fitness effects of spontaneous mutations in Chlamydomonas reinhardtii
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DOI：
10.1371/journal.pbio.3000192
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发表时间：
2019-06-01
期刊：
影响因子：
9.8
通讯作者：
Keightley, Peter D.
中科院分区：
文献类型：
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作者：
Bondel, Katharina B.;Kraemer, Susanne A.;Keightley, Peter D.
自发突变是新遗传变异的来源，因此是进化过程的核心。在分子进化和数量遗传学中，遗传变异的性质关键取决于突变对适应性和其他数量性状的影响的分布。自发突变积累（MA）实验一直是研究突变总体发生率和累积效应的主要方法，但不允许直接研究单个突变的表型效应。在这里，我们将绿藻莱茵衣藻的 MA 系与其未突变的祖先菌株杂交，创建单倍体重组系，每个重组系平均携带大量组合中累积突变的 50%。借助 MA 系的基因组序列，我们推断了突变的基因型，测定了它们的生长率作为适应性的衡量标准，并使用贝叶斯混合模型推断了适应性效应 (DFE) 的分布。我们推断 DFE 是高度峰态的（L 形）。在绝对适应度影响超过 1% 的突变中，大约六分之一的突变会增加实验室环境中的适应度。推断出的有害突变的影响分布与近中性进化的强大作用是一致的。具体来说，这种分布预测数量性状的核苷酸变异和遗传变异将对有效种群规模的变化不敏感。
Spontaneous mutations are the source of new genetic variation and are thus central to the evolutionary process. In molecular evolution and quantitative genetics, the nature of genetic variation depends critically on the distribution of effects of mutations on fitness and other quantitative traits. Spontaneous mutation accumulation (MA) experiments have been the principal approach for investigating the overall rate of occurrence and cumulative effect of mutations but have not allowed the phenotypic effects of individual mutations to be studied directly. Here, we crossed MA lines of the green alga Chlamydomonas reinhardtii with its unmutated ancestral strain to create haploid recombinant lines, each carrying an average of 50% of the accumulated mutations in a large number of combinations. With the aid of the genome sequences of the MA lines, we inferred the genotypes of the mutations, assayed their growth rate as a measure of fitness, and inferred the distribution of fitness effects (DFE) using a Bayesian mixture model. We infer that the DFE is highly leptokurtic (L-shaped). Of mutations with absolute fitness effects exceeding 1%, about one-sixth increase fitness in the laboratory environment. The inferred distribution of effects for deleterious mutations is consistent with a strong role for nearly neutral evolution. Specifically, such a distribution predicts that nucleotide variation and genetic variation for quantitative traits will be insensitive to change in the effective population size.