WHOLE-GENOME SEQUENCING OF A LABORATORY-EVOLVED YEAST STRAIN

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 背景技术背景：微生物种群的实验进化提供了一个独特的机会，研究进化适应控制选择压力。然而，直到最近，在全基因组范围内确定适应的精确遗传变化一直很困难。新的DNA测序技术现在可以快速确定微生物的亲本和进化菌株的基因组。结果：我们对实验室进化的酿酒酵母菌株及其祖先的>93.5%的基因组进行了测序，深度> 28倍。单核苷酸多态性和拷贝数扩增都被发现，与以前用于分析这些基因组的基于阵列的方法相比有特定的收获。应用分割算法来量化结构变化，我们确定了5x基因扩增的近似基因组边界。这些边界引导断点序列的恢复，这提供了对复杂基因组重排的性质的见解。结论：这项研究表明，全基因组测序可以提供一种快速的方法来揭示进化适应的遗传基础，并进一步应用于实验室选择和诱变筛选的研究。此外，我们还展示了单端短读测序数据如何提供有关结构重排的详细信息，并生成有关基因组可塑性基础的基因组特征和过程的预测。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. BACKGROUND: Experimental evolution of microbial populations provides a unique opportunity to study evolutionary adaptation in response to controlled selective pressures. However, until recently it has been difficult to identify the precise genetic changes underlying adaptation at a genome-wide scale. New DNA sequencing technologies now allow the genome of parental and evolved strains of microorganisms to be rapidly determined. RESULTS: We sequenced >93.5% of the genome of a laboratory-evolved strain of the yeast Saccharomyces cerevisiae and its ancestor at >28x depth. Both single nucleotide polymorphisms and copy number amplifications were found, with specific gains over array-based methodologies previously used to analyze these genomes. Applying a segmentation algorithm to quantify structural changes, we determined the approximate genomic boundaries of a 5x gene amplification. These boundaries guided the recovery of breakpoint sequences, which provide insights into the nature of a complex genomic rearrangement. CONCLUSIONS: This study suggests that whole-genome sequencing can provide a rapid approach to uncover the genetic basis of evolutionary adaptations, with further applications in the study of laboratory selections and mutagenesis screens. In addition, we show how single-end, short read sequencing data can provide detailed information about structural rearrangements, and generate predictions about the genomic features and processes that underlie genome plasticity.