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Direct estimation of per nucleotide and genomic deleterious mutation rates in Drosophila

机译：直接估计果蝇中每个核苷酸和基因组有害突变率

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摘要

Spontaneous mutations are the source of genetic variation required for evolutionary change, and are therefore important for many aspects of evolutionary biology. For example, the divergence between taxa at neutrally evolving sites in the genome is proportional to the per nucleotide mutation rate, u (ref. 1), and this can be used to date speciation events by assuming a molecular clock. The overall rate of occurrence of deleterious mutations in the genome each generation (U) appears in theories of nucleotide divergence and polymorphism(2), the evolution of sex and recombination(3), and the evolutionary consequences of inbreeding(2). However, estimates of U based on changes in allozymes(4) or DNA sequences(5) and fitness traits are discordant(6-8). Here we directly estimate u in Drosophila melanogaster by scanning 20 million bases of DNA from three sets of mutation accumulation lines by using denaturing high-performance liquid chromatography(9). From 37 mutation events that we detected, we obtained a mean estimate for u of 8.4 x 10(-9) per generation. Moreover, we detected significant heterogeneity in u among the three mutation-accumulation-line genotypes. By multiplying u by an estimate of the fraction of mutations that are deleterious in natural populations of Drosophila(10), we estimate that U is 1.2 per diploid genome. This high rate suggests that selection against deleterious mutations may have a key role in explaining patterns of genetic variation in the genome, and help to maintain recombination and sexual reproduction.
机译：自发突变是进化变化所需的遗传变异的来源，因此对于进化生物学的许多方面都非常重要。例如，在基因组中性进化位点的分类单元之间的差异与每个核苷酸突变率u（ref。1）成正比，可以通过假设分子时钟来将其用于物种形成事件。每代（U）的基因组中有害突变的总体发生率出现在核苷酸发散和多态性（2），性别和重组的进化（3）以及近交的进化后果（2）的理论中。但是，基于同工酶（4）或DNA序列（5）和适应性状的变化对U的估计是不一致的（6-8）。在这里我们通过变性高效液相色谱法从三组突变积累系中扫描2000万个DNA碱基来直接估计果蝇中的u（9）。从我们检测到的37个突变事件中，我们获得了每代u的平均估计值8.4 x 10（-9）。此外，我们在三种突变积累线基因型之间的u中检测到显着的异质性。通过将u乘以果蝇自然种群中有害突变的分数的估计值，我们估计每个二倍体基因组U为1.2。如此高的比率表明，针对有害突变的选择可能在解释基因组中遗传变异的模式中起关键作用，并有助于维持重组和有性繁殖。

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