Ribosomal DNA genes (rDNA) encode the major ribosomal RNAs (rRNA) and in eukaryotic genomes are typically present as one or more arrays of tandem repeats. Species have characteristic rDNA copy numbers, ranging from tens to thousands of copies, with the number thought to be redundant for rRNA production. However, the tandem rDNA repeats are prone to recombination-mediated changes in copy number, resulting in substantial intra-species copy number variation. There is growing evidence that these copy number differences can have phenotypic consequences. However, we lack a comprehensive understanding of what determines rDNA copy number, how it evolves, and what the consequences are, in part because of difficulties in quantifying copy number. Here, we developed a genomic sequence read approach that estimates rDNA copy number from the modal coverage of the rDNA and whole genome to help overcome limitations in quantifying copy number with existing mean coverage-based approaches. We validated our method using strains of the yeast Saccharomyces cerevisiae with previously-determined rDNA copy numbers, and then applied our pipeline to investigate rDNA copy number in a global sample of 788 yeast isolates. We found that wild yeast have a mean copy number of 92, consistent with what is reported for other fungi but much lower than in laboratory strains. We show that different populations have different rDNA copy numbers. These differences can partially be explained by phylogeny, but other factors such as environment are also likely to contribute to population differences in copy number. Our results demonstrate the utility of the modal coverage method, and highlight the high level of rDNA copy number variation within and between populations.

中文翻译：

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确定核糖体DNA拷贝数的新方法显示了酿酒酵母种群之间的差异

核糖体DNA基因（rDNA）编码主要的核糖体RNA（rRNA），在真核生物基因组中通常以一个或多个串联重复序列的形式存在。物种具有特征性的rDNA拷贝数，范围从几十个到数千个拷贝，该数目被认为对于生产rRNA是多余的。但是，串联rDNA重复序列易于重组介导的拷贝数变化，导致种内拷贝数大量变化。越来越多的证据表明，这些拷贝数差异会产生表型后果。但是，我们对rDNA拷贝数的决定因素，它的进化方式和后果缺乏全面的了解，部分原因是难以量化拷贝数。这里，我们开发了一种基因组序列读取方法，可从rDNA和整个基因组的模态覆盖范围估算rDNA拷贝数，以克服现有的基于均数覆盖的方法在量化拷贝数方面的局限性。我们使用先前确定的rDNA拷贝数的酿酒酵母菌株验证了我们的方法，然后应用我们的管道研究了788个酵母菌的全球样本中的rDNA拷贝数。我们发现野生酵母的平均拷贝数为92，与其他真菌报道的一致，但远低于实验室菌株。我们显示不同的人群具有不同的rDNA拷贝数。这些差异可以通过系统发生学部分地解释，但是其他因素（例如环境）也可能导致拷贝数上的种群差异。