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.本数据集采用的比较基因组杂交（Comparative Genomic Hybridization, CGH）芯片源自Smukowski Heil等人2017年发表于《Molecular Biology and Evolution》（简称MBE）的研究。杂交通常被认为是适应不良的，但有时杂种可侵入新的生态位，并比亲本更能适应全新或胁迫环境。杂交后发生的、有助于基因组整合与/或适应性演化的基因组变化，其内在机制尚未得到充分解析。本研究以全新构建的种间杂交酵母——酿酒酵母（Saccharomyces cerevisiae）×乌瓦鲁姆酵母（Saccharomyces uvarum）——及其亲本菌株为实验对象，通过实验演化手段探究上述问题。我们将这些菌株置于营养限制条件下演化数百代，并对最终获得的培养物进行测序，以鉴定基因组层面的变化。通过对16株杂种克隆与16株亲本克隆的分析，我们鉴定出大量点突变、拷贝数变异以及杂合性丢失事件，其中包括营养转运蛋白的物种偏好性扩增。我们重点关注了一个极具研究价值的案例：在种内与种间杂种中，均观察到高亲和性磷酸转运蛋白基因PHO84位点反复发生杂合性丢失。我们通过等位基因替换技术，分别在杂种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：在酿酒酵母与杂种中，杂合性丢失均源于对其中一种等位基因的正向选择。本研究为“杂种基因组整合由基于现存杂合性的正向选择所驱动”提供了实例，并证实即便是罕见的远缘杂交，也可能对适应性演化产生持久影响。