Saccharomyces cerevisiae strain:YJM311 Genome sequencing and assembly. Saccharomyces cerevisiae strain:YJM311

The budding yeast Saccharomyces cerevisiae has been extensively characterized for many decades and is a critical resource for the study of numerous facets of eukaryotic biology. Recently, whole genome sequence analysis of over 1000 natural isolates of S. cerevisiae has provided critical insights into the evolutionary landscape of this species by revealing a population structure comprised of numerous genomically diverse lineages. These survey-level analyses have been largely devoid of structural genomic information, mainly because short read sequencing is not suitable for detailed characterization of genomic architecture. Consequently, we still lack a complete perspective of the genomic variation the exists within the species. Single molecule long read sequencing technologies, such as Oxford Nanopore and PacBio, provide sequencing-based approaches with which to rigorously define the structure of a genome, and have empowered yeast geneticists to explore this poorly described realm of eukaryotic genomics. Here, we present the comprehensive genomic structural analysis of a wild diploid isolate of S. cerevisiae, YJM311. We used long read sequence analysis to construct a haplotype-phased, telomere-to-telomere length assembly of the YJM311 genome and characterized the structural variations (SVs) therein. We discovered that the genome of YJM311 contains significant intragenomic structural variation, some of which imparts notable consequences to the genomic stability and developmental biology of the strain. Collectively, we outline a new methodology for creating accurate haplotype-phased genome assemblies and highlight how such genomic analyses can define the structural architectures of S. cerevisiae isolates. It is our hope that continued structural characterization of S. cerevisiae genomes, such as we have reported here for YJM311, will comprehensively advance our understanding of eukaryotic genome structure-function relationships, structural genomic diversity, and evolution.

酿酒酵母（Saccharomyces cerevisiae）作为经典模式生物已被广泛研究数十年，是探究真核生物生物学诸多维度的关键实验资源。近期，针对超过1000株酿酒酵母自然分离株的全基因组序列分析，揭示了该物种由多个基因组异质性谱系构成的群体结构，为其进化图谱提供了关键性洞见。此类概览级分析大多缺失结构基因组学数据，核心原因在于短读长测序技术难以实现基因组结构的精细表征。故此，我们至今仍未能完整认知该物种内部存在的基因组变异全貌。单分子长读长测序技术（single molecule long read sequencing technologies），如牛津纳米孔（Oxford Nanopore）与PacBio，为精准解析基因组结构提供了可行的测序研究手段，也助力酵母遗传学家探索真核基因组学中这一尚未被充分阐释的研究领域。本研究针对一株野生二倍体酿酒酵母分离株YJM311，开展了全面的基因组结构分析。我们借助长读长测序分析，构建了YJM311基因组的单倍型分型（haplotype-phased）、端粒到端粒（telomere-to-telomere）长度的组装结果，并对其中的结构变异（structural variations, SVs）进行了系统表征。研究发现，YJM311的基因组存在显著的基因组内结构变异，其中部分变异对该菌株的基因组稳定性与发育生物学特征具有显著影响。综上，我们提出了一套构建精准单倍型分型基因组组装的全新方法，并阐释了此类基因组分析如何精准界定酿酒酵母分离株的结构架构。我们期望，如同本研究针对YJM311所开展的结构表征工作一般，对酿酒酵母基因组的持续结构解析，将全面推进我们对真核生物基因组结构-功能关系、结构基因组多样性以及物种进化的认知。