Evolution of Yeast Respiro-Fermentative Lifestyle and the Underlying Mechanisms Behind Aerobic Fermentation

Abstract: Under aerobic conditions, most yeasts such as Kluyveromyces lactis, prefer the respiratory pathway and some, such as Saccharomyces cerevisiae prefer less energy efficient fermentative pathway for their energy metabolism. These two metabolic strategies are also known as Crabtree negative and Crabtree positive respectively, and the evolution of the latter has lately been explained by the “make-accumulate-consume” life strategy. Scientists have for more than a century tried to elucidate the mechanism behind the physiology and the evolution of the peculiar respiro-fermentation trait. During the last decades, comparative genomics approaches have enabled the reconstruction of the evolutionary history of yeast, and several evolutionary events have been identified and postulated to have contributed to the development of the respiro-fermentative lifestyle in the Saccharomyces lineage. However, many of these inspiring studies have been verified with reference species only. Therefore, as parts of my thesis I conducted large-scale physiology studies of more than 40 yeast species and their central carbon metabolism under controlled conditions, in bioreactors. This was done in order to map the evolution of aerobic fermentation in yeast belonging to the Saccharomyces lineage that span over 200 million years of yeast evolution. This evolutionary blueprint, which most likely will be an invaluable information source of primary data for future in silico studies on the evolution of Crabtree effect, has already verified the importance of evolutionary events, such as promoter rewiring, chromatin relaxation, whole genome duplication, gene duplication and lateral gene-transfers. I further propose a mechanism that provides an explanation for the origin of the respiro-fermentative lifestyle in yeast, and how this was subsequently, through a multistep process developed into the Crabtree effect as we know it in the modern yeasts today, such as S. cerevisiae and its sister species.