Loss of heterozygosity drives adaptation in hybrid yeast

CGH arrays for Smukowski Heil, et al MBE 2017. Hybridization is often considered maladaptive, but sometimes hybrids can invade new ecological niches and adapt to novel or stressful environments better than their parents. The genomic changes that occur following hybridization that facilitate genome resolution and/or adaptation are not well understood. Here, we address these questions using experimental evolution of de novo interspecific hybrid yeast Saccharomyces cerevisiae x Saccharomyces uvarum and their parentals. We evolved these strains in nutrient limited conditions for hundreds of generations and sequenced the resulting cultures to identify genomic changes. Analysis of 16 hybrid clones and 16 parental clones identified numerous point mutations, copy number changes, and loss of heterozygosity events, including species biased amplification of nutrient transporters. We focused on a particularly interesting example, in which we saw repeated loss of heterozygosity at the high affinity phosphate transporter gene PHO84 in both intra- and interspecific hybrids. Using allele replacement methods, we tested the fitness of different alleles in hybrid and S. cerevisiae strain backgrounds and found that the loss of heterozygosity is indeed the result of selection on one allele over the other in both S. cerevisiae and the hybrids. This is an example where hybrid genome resolution is driven by positive selection on existing heterozygosity, and demonstrates that even infrequent outcrossing may have lasting impacts on adaptation. Each CGH array is a comparison of the DNA content of an evolved yeast population vs the matched ancestor.

本数据集为Smukowski Heil等人2017年发表于《分子生物学与进化》（Molecular Biology and Evolution，MBE）的研究所用的比较基因组杂交芯片（Comparative Genomic Hybridization, CGH）。杂交常被视作适应不良的过程，但部分杂交子代可开拓全新生态位，且相较于亲本更能适应新颖或胁迫环境。目前学界对杂交后发生的、可促进基因组解析与适应性演化的基因组变化机制尚缺乏充分认知。本研究通过对从头构建的酿酒酵母（Saccharomyces cerevisiae）×乌瓦酵母（Saccharomyces uvarum）种间杂交菌株及其亲本开展实验演化，对上述问题展开探讨。我们将这些菌株置于营养限制条件下传代培养数百代，随后对最终培养物进行测序以鉴定基因组变异。通过对16株杂交克隆与16株亲本克隆的分析，共检出大量点突变、拷贝数变异及杂合性丢失事件，其中涵盖营养转运蛋白的物种偏好性扩增。我们重点聚焦于一个极具研究价值的现象：在种内与种间杂交后代中，均反复观测到高亲和力磷酸盐转运蛋白基因PHO84位点的杂合性丢失。借助等位基因替换技术，我们在杂交背景与酿酒酵母菌株背景中检测了不同等位基因的适合度，结果证实，无论是在酿酒酵母还是杂交菌株中，该位点的杂合性丢失均源于对其中一个等位基因的正向选择。本研究表明，杂交基因组的解析可由对现存杂合性的正向选择所驱动，同时证实即便是低频远缘杂交，也可能对适应性演化产生持久影响。每一块CGH芯片均用于对比演化酵母种群与其对应祖先的DNA含量。