Scott Amber L, Richmond Phillip A, Dowell Robin D, Selmecki Anna M
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO.
BioFrontiers Institute, University of Colorado, Boulder, CO.
Mol Biol Evol. 2017 Oct 1;34(10):2690-2703. doi: 10.1093/molbev/msx205.
Polyploidization events have occurred during the evolution of many fungi, plant, and animal species and are thought to contribute to speciation and tumorigenesis, however little is known about how ploidy level contributes to adaptation at the molecular level. Here we integrate whole genome sequencing, RNA expression analysis, and relative fitness of ∼100 evolved clones at three ploidy levels. Independent haploid, diploid, and tetraploid populations were grown in a low carbon environment for 250 generations. We demonstrate that the key adaptive mutation in the evolved clones is predicted by a gene expression signature of just five genes. All of the adaptive mutations identified encompass a narrow set of genes, however the tetraploid clones gain a broader spectrum of adaptive mutations than haploid or diploid clones. While many of the adaptive mutations occur in genes that encode proteins with known roles in glucose sensing and transport, we discover mutations in genes with no canonical role in carbon utilization (IPT1 and MOT3), as well as identify novel dominant mutations in glucose signal transducers thought to only accumulate recessive mutations in carbon limited environments (MTH1 and RGT1). We conclude that polyploid cells explore more genotypic and phenotypic space than lower ploidy cells. Our study provides strong evidence for the beneficial role of polyploidization events that occur during the evolution of many species and during tumorigenesis.
多倍体化事件在许多真菌、植物和动物物种的进化过程中均有发生，并且被认为对物种形成和肿瘤发生有促进作用，然而，关于倍性水平如何在分子层面上促进适应性，人们却知之甚少。在此，我们整合了全基因组测序、RNA表达分析以及大约100个在三种倍性水平下进化的克隆的相对适应性。独立的单倍体、二倍体和四倍体群体在低碳环境中生长了250代。我们证明，进化克隆中的关键适应性突变可由仅五个基因的基因表达特征预测。所有鉴定出的适应性突变都包含在一组范围狭窄的基因中，然而，四倍体克隆获得的适应性突变谱比单倍体或二倍体克隆更广泛。虽然许多适应性突变发生在编码在葡萄糖感知和转运中具有已知作用的蛋白质的基因中，但我们在碳利用方面没有典型作用的基因（IPT1和MOT3）中发现了突变，并且在葡萄糖信号转导因子中鉴定出了新的显性突变，这些信号转导因子被认为在碳限制环境中只会积累隐性突变（MTH1和RGT1）。我们得出结论，多倍体细胞比低倍体细胞探索了更多的基因型和表型空间。我们的研究为许多物种进化过程中以及肿瘤发生过程中发生的多倍体化事件的有益作用提供了有力证据。
