Department of Genetics, Stanford University, Stanford, CA, USA.
Department of Biology, Stanford University, Stanford, CA, USA.
BMC Ecol Evol. 2021 Sep 29;21(1):185. doi: 10.1186/s12862-021-01915-5.
Natural selection can act on multiple genes in the same pathway, leading to polygenic adaptation. For example, adaptive changes were found to down-regulate six genes involved in ergosterol biosynthesis-an essential pathway targeted by many antifungal drugs-in some strains of the yeast Saccharomyces cerevisiae. However, the impact of this polygenic adaptation on metabolite levels was unknown. Here, we performed targeted mass spectrometry to measure the levels of eight metabolites in this pathway in 74 yeast strains from a genetic cross.
Through quantitative trait locus (QTL) mapping we identified 19 loci affecting ergosterol pathway metabolite levels, many of which overlap loci that also impact gene expression within the pathway. We then used the recently developed v-test, which identified selection acting upon three metabolite levels within the pathway, none of which were predictable from the gene expression adaptation.
These data showed that effects of selection on metabolite levels were complex and not predictable from gene expression data. This suggests that a deeper understanding of metabolism is necessary before we can understand the impacts of even relatively straightforward gene expression adaptations on metabolic pathways.
自然选择可以在同一途径中的多个基因上起作用，从而导致多基因适应。例如，在一些酵母 Saccharomyces cerevisiae 菌株中，发现适应性变化下调了涉及麦角固醇生物合成的六个基因，这是许多抗真菌药物的关键途径。然而，这种多基因适应对代谢物水平的影响尚不清楚。在这里，我们通过靶向质谱法测量了遗传杂交产生的 74 株酵母菌株中该途径的八种代谢物的水平。
通过数量性状位点 (QTL) 映射，我们鉴定出了 19 个影响麦角固醇途径代谢物水平的基因座，其中许多基因座与该途径中基因表达的基因座重叠。然后，我们使用了最近开发的 v 检验，该检验鉴定出了该途径中三个代谢物水平的选择作用，其中没有一个可从基因表达适应中预测。
这些数据表明，选择对代谢物水平的影响是复杂的，不能从基因表达数据中预测。这表明，在我们能够理解即使是相对简单的基因表达适应对代谢途径的影响之前，我们需要更深入地了解代谢。
