title: The meiotic-mitotic initiation switch in budding yeast maintains its function robustly against sensitive parameter perturbations.
abstract: Experiments show that the meiotic-mitotic initiation switch in budding yeast functions robustly during the early hours of meiosis initiation. In this study, we explain these experimental observations first by understanding how this switching occurs during the early hours of meiosis by studying the temporal variation of this switch at the gene expression level. Then, we investigate the effects on this meiotic-mitotic switching from the perturbations of the most sensitive parameters in budding yeast meiosis initiation network. We use a mathematical model of meiosis initiation in budding yeast for this task and find the most sensitive group of parameters that influence the expressions of meiosis and mitosis initiators at all stages of the meiotic-mitotic switch. The results indicate that the transition region of the switch, where a double negative feedback loop between meiosis (Ime2) and mitosis (Cdk1/Cln3) initiators plays a major role, shows lower robustness. Feedback loops are frequently observed serving as a major robust adaption mechanism in many biological networks. Consequences of this less robust region appear in the transition region of the resulting switches. Most importantly, despite the differences observed in the transition region, we find that the meiotic-mitotic switch robustly maintains its main function of transition from meiosis to mitosis when the nutrients are re-supplied, against the perturbations in the sensitive parameters.
authors.affiliation: Centre for Advanced Computational Solutions (C-fACS), Department of Molecular Biosciences, Lincoln University, Christchurch, New Zealand.
authors.forename: C T
authors.initials: CT
authors.lastname: Wannige
authors.affiliation: Centre for Advanced Computational Solutions (C-fACS), Department of Molecular Biosciences, Lincoln University, Christchurch, New Zealand. Electronic address: don.kulasiri@lincoln.ac.nz.
authors.forename: D
authors.initials: D
authors.lastname: Kulasiri
authors.affiliation: Centre for Advanced Computational Solutions (C-fACS), Department of Molecular Biosciences, Lincoln University, Christchurch, New Zealand.
authors.forename: S
authors.initials: S
authors.lastname: Samarasinghe
mesh_terms: D008540:Meiosis; D008938:Mitosis; D008962:Models, Theoretical; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000502:physiology*
keywords: Bistability; Local and global sensitivity analyses; Meiosis; Mitosis; Robustness