Ho Ping-Wei, Piampongsant Supinya, Gallone Brigida, Del Cortona Andrea, Peeters Pieter-Jan, Reijbroek Frank, Verbaet Jules, Herrera Beatriz, Cortebeeck Jeroen, Nolmans Robbe, Saels Veerle, Steensels Jan, Jarosz Daniel F, Verstrepen Kevin J
VIB-KU Leuven Center for Microbiology, Leuven, Belgium.
CMPG Laboratory of Genetics and Genomics, Department M2S, KU Leuven, Leuven, Belgium.
Biotechnol Biofuels. 2021 Nov 2;14(1):211. doi: 10.1186/s13068-021-02059-w.
The brewer's yeast Saccharomyces cerevisiae is exploited in several industrial processes, ranging from food and beverage fermentation to the production of biofuels, pharmaceuticals and complex chemicals. The large genetic and phenotypic diversity within this species offers a formidable natural resource to obtain superior strains, hybrids, and variants. However, most industrially relevant traits in S. cerevisiae strains are controlled by multiple genetic loci. Over the past years, several studies have identified some of these QTLs. However, because these studies only focus on a limited set of traits and often use different techniques and starting strains, a global view of industrially relevant QTLs is still missing.
Here, we combined the power of 1125 fully sequenced inbred segregants with high-throughput phenotyping methods to identify as many as 678 QTLs across 18 different traits relevant to industrial fermentation processes, including production of ethanol, glycerol, isobutanol, acetic acid, sulfur dioxide, flavor-active esters, as well as resistance to ethanol, acetic acid, sulfite and high osmolarity. We identified and confirmed several variants that are associated with multiple different traits, indicating that many QTLs are pleiotropic. Moreover, we show that both rare and common variants, as well as variants located in coding and non-coding regions all contribute to the phenotypic variation.
Our findings represent an important step in our understanding of the genetic underpinnings of industrially relevant yeast traits and open new routes to study complex genetics and genetic interactions as well as to engineer novel, superior industrial yeasts. Moreover, the major role of rare variants suggests that there is a plethora of different combinations of mutations that can be explored in genome editing.
酿酒酵母在多个工业过程中都有应用，从食品和饮料发酵到生物燃料、药品和复杂化学品的生产。该物种内巨大的遗传和表型多样性为获得优良菌株、杂种和变体提供了丰富的自然资源。然而，酿酒酵母菌株中大多数与工业相关的性状是由多个基因位点控制的。在过去几年中，多项研究已经鉴定出了其中一些数量性状基因座（QTL）。然而，由于这些研究仅关注有限的一组性状，并且经常使用不同的技术和起始菌株，因此仍然缺乏对与工业相关的QTL的全局认识。
在这里，我们将1125个完全测序的近交分离株的优势与高通量表型分析方法相结合，以鉴定出与工业发酵过程相关的18种不同性状的多达678个QTL，包括乙醇、甘油、异丁醇、乙酸、二氧化硫、风味活性酯的生产，以及对乙醇、乙酸、亚硫酸盐和高渗透压的抗性。我们鉴定并确认了几个与多种不同性状相关的变体，这表明许多QTL具有多效性。此外，我们表明罕见和常见变体以及位于编码区和非编码区的变体都对表型变异有贡献。
我们的发现代表了我们在理解与工业相关的酵母性状的遗传基础方面迈出的重要一步，并为研究复杂遗传学和遗传相互作用以及改造新型优良工业酵母开辟了新途径。此外，罕见变体的主要作用表明，在基因组编辑中可以探索大量不同的突变组合。
