Data_Sheet_1_Comparative Genomic and Transcriptomic Analysis Reveals Specific Features of Gene Regulation in Kluyveromyces marxianus.DOCX

Kluyveromyces marxianus is a promising host for producing bioethanol and heterologous proteins. It displays many superior traits to a conventional industrial yeast species, Saccharomyces cerevisiae, including fast growth, thermotolerance and the capacity to assimilate a wider variety of sugars. However, little is known about the mechanisms underlying the fast-growing feature of K. marxianus. In this study, we performed a comparative genomic analysis between K. marxianus and other Saccharomycetaceae species. Genes involved in flocculation, iron transport, and biotin biosynthesis have particularly high copies in K. marxianus. In addition, 60 K. marxianus specific genes were identified, 45% of which were upregulated during cultivation in rich medium and these genes may participate in glucose transport and mitochondrion related functions. Furthermore, the transcriptomic analysis revealed that under aerobic condition, normalized levels of genes participating in TCA cycles, respiration chain and ATP biosynthesis in the lag phase were higher in K. marxianus than those in S. cerevisiae. Levels of highly copied genes, genes involved in the respiratory chain and mitochondrion assembly, were upregulated in K. marxianus, but not in S. cerevisiae, in later time points during cultivation compared with those in the lag phase. Notably, during the fast-growing phase, genes involved in the respiratory chain, ATP synthesis and glucose transport were co-upregulated in K. marxianus. A few shared motifs in upstream sequences of relevant genes might result in the co-upregulation. Specific features in the co-regulations of gene expressions might contribute to the fast-growing phenotype of K. marxianus. Our study underscores the importance of genome-wide rewiring of the transcriptional network during evolution.

克鲁维酵母（Kluyveromyces marxianus）作为一种具有潜力的生物乙醇和异源蛋白生产宿主，展现出诸多优于传统工业酵母物种酿酒酵母（Saccharomyces cerevisiae）的优异特性，诸如快速生长、耐热性以及对更广泛糖类的同化能力。然而，关于K. marxianus快速生长机制的认知尚显不足。在本研究中，我们对K. marxianus与其它酿酒酵母科物种进行了比较基因组分析。在K. marxianus中，参与絮凝、铁转运和生物素生物合成的基因拷贝数尤为突出。此外，共鉴定出60个K. marxianus特异性基因，其中45%在富营养培养基培养过程中表达上调，这些基因可能参与葡萄糖转运和线粒体相关功能。进一步地，转录组分析揭示，在需氧条件下，K. marxianus在延滞期的三羧酸循环、呼吸链和ATP生物合成的基因标准化水平高于酿酒酵母。与延滞期相比，在培养后期，K. marxianus中高度拷贝基因、参与呼吸链和线粒体组装的基因水平上调，而在酿酒酵母中则未观察到此现象。值得注意的是，在快速生长阶段，K. marxianus中参与呼吸链、ATP合成和葡萄糖转运的基因协同上调。相关基因上游序列中的一些共有基序可能导致这种协同上调。基因表达共调控的特定特征可能有助于K. marxianus快速生长表型的形成。本研究强调了在进化过程中转录网络全局重排的重要性。