Abstract
Signaling pathways enable cells to sense and respond to their environment. Many cellular signaling strategies are conserved from fungi to humans, yet their activity and phenotypic consequences can vary extensively among individuals within a species. A systematic assessment of the impact of naturally occurring genetic variation on signaling pathways remains to be conducted. In S. cerevisiae, both response and resistance to stressors that activate signaling pathways differ between diverse isolates. Here, we present a quantitative trait locus (QTL) mapping approach that enables us to identify genetic variants underlying such phenotypic differences across the genetic and phenotypic diversity of S. cerevisiae. Using a Round-robin cross between twelve diverse strains, we identified QTL that influence phenotypes critically dependent on MAPK signaling cascades. Genetic variants under these QTL fall within MAPK signaling networks themselves as well as other interconnected signaling pathways. Finally, we demonstrate how the mapping results from multiple strain background can be leveraged to narrow the search space of causal genetic variants.
Highlights
Cellular survival is dependent on the ability to sense and respond to changing environmental conditions
Insults to the cell wall are sensed by the cell-wall integrity (CWI) pathway, which is anchored by the Mitogen-activated protein kinase (MAPK) Slt2, homolog of the mammalian MAPK7 [7]
We have developed an approach to facilitate the mapping of genetic variants that underlie these phenotypic differences in a set of wild strain
Summary
Cellular survival is dependent on the ability to sense and respond to changing environmental conditions. Insults to the cell wall are sensed by the cell-wall integrity (CWI) pathway, which is anchored by the MAPK Slt, homolog of the mammalian MAPK7 [7] While these pathways have been scrutinized in great detail, it remains largely unknown how they are affected by genetic variation among different yeast isolates. While genes of the core MAPK cascades are highly conserved across species, upstream regulatory components, such as stress sensors, and downstream targets, such as transcription factors, exhibit high levels of divergence [11,12]. It is unknown how genetic differences in such elements of the MAPK pathways contribute to the phenotypic differences between isolates of the same species. We sought to examine how sequence variation among yeast isolates results in quantitative differences in MAPK-dependent phenotypes
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
