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Experimental evolution of Saccharomyces cerevisiae for caffeine tolerance alters multidrug resistance and target of rapamycin signaling pathways

2024; Genetics Society of America; Volume: 14; Issue: 9 Linguagem: Inglês

10.1093/g3journal/jkae148

2160-1836

Renee C. Geck, Naomi G. Moresi, L. Anderson, Isabel Addepalli, Deepti Aggarwal, Prisha Agnihotri, Ahlaam A Ali, Clara J. Amorosi, Abhinav Anand, Ashna Atukuri, Thang Awi, Insiya Basrai, Hitha Bathala, Soham M. Bhide, Benjamin B Cantor, Jocelyn Cervantes, Tridib Chakraborty, James Champlin, Ameen Chbihi, Felicia Chen, Hayley Chenfang, Reagan Choi, Sebastian Chokka, Julian D'Souza, Vivek Dandu, Arkesh Das, M.D. HEND TAMIM MARIAM DAWOUD, Victoria Dong, Riya Dutta, Graeme Edoff, Cecelia Fan, Rena Foo, Liam T Glanville, Cristian Golat, Suhavi Grewal, Faye Guan, Aarya Gurav, Aranav Gupta, Krish Gupta, S. M. Gupta, Osman Hameed, Rhea Hede-Sakhardande, Nushaba Hossain, Youssef Ibrahim, Jemi Isaac, Udayvir Jalf, Medha Jasti, Amar Jazvin, Okichy Johnny, Vidhi Kamat, Venya Kandula, Lekhana Katuri, Keabe E Kebede, Om Khuperkar, Emily Kim, Rishi Konduru, Salimah Kyaw, Daniel J. Lee, Tian Syun Lin, Karen Luo, Jwan Magsoosi, Mlahat Mahmood, Ronald Brent F Marzan, Noyonima Masud, Jessica H. Mathew, Ava Miciuda, Trevor Morey, Anagha Nair, N. Natarajan, Aahil Abdul Nazeer, Usoatua Levei P Noa, Shashank Pagadala, Hamin Paik, Javier Pinilla Palomino, Kush Parikh, N L Phadke, Michelle V Phan, Britta Pingree, Neal Podhuturi, Arya Prasad, Sonia Puri, Sanjini Rajkumar, Ananya Ramanan, Elliot M Russell, Zachary L Saad, M. Gaytán, Francis L Salazar, Anjali Sanil, Neespruha Shah, Mustafa Sharba, Prihensha Sharma, Sophia Showman, Soyeon Showman, Heejin Shyn, Aryan Singh, Saakshi Sovani, Shreya Srugaram, Rachel Stroia, Sanjana Sunilkumar, Nihil Suthy, Asma Syed, Ruthesh Thavamani, Nitya Upadhye, R. Varghese, Annie Wang, Cynthia Wang, Ruizhe Wang, Miya A Watson, Theresa Wei, Myra L Woody, Nancy Yao, Tyler Yee, Chiann-Ling C Yeh, Jungbin Yoon, Jiaying Zhou, Tianhui Zhu, Noah Fredstrom, Sandra Pennington, Scarlett Counihan, Owen Burris, Marisol Jimenez Garcia, Dennis Godin, Rebecca Brewer, Timothy R. Renz, M. Bryce Taylor, Maitreya J. Dunham,

Fungal and yeast genetics research

Caffeine is a natural compound that inhibits the major cellular signaling regulator target of rapamycin (TOR), leading to widespread effects including growth inhibition. Saccharomyces cerevisiae yeast can adapt to tolerate high concentrations of caffeine in coffee and cacao fermentations and in experimental systems. While many factors affecting caffeine tolerance and TOR signaling have been identified, further characterization of their interactions and regulation remain to be studied. We used experimental evolution of S. cerevisiae to study the genetic contributions to caffeine tolerance in yeast, through a collaboration between high school students evolving yeast populations coupled with further research exploration in university labs. We identified multiple evolved yeast populations with mutations in PDR1 and PDR5, which contribute to multidrug resistance, and showed that gain-of-function mutations in multidrug resistance family transcription factors Pdr1, Pdr3, and Yrr1 differentially contribute to caffeine tolerance. We also identified loss-of-function mutations in TOR effectors Sit4, Sky1, and Tip41 and showed that these mutations contribute to caffeine tolerance. These findings support the importance of both the multidrug resistance family and TOR signaling in caffeine tolerance and can inform future exploration of networks affected by caffeine and other TOR inhibitors in model systems and industrial applications.