內共生，表現型穩定性和物種演化的一般原理和分子機制

1) 利用基因體分析來瞭解草履蟲和小球藻內共生的關係

為什麼一個生物可以活在另一個生物體內而不會引起問題呢？內共生 是驅動真核細胞演化的主要力量之一（粒線體與葉綠體是最有名的例 子），在當今自然界中也隨處可見內共生的例子。然而，共生體如何在 宿主細胞中建立內共生的過機制至今仍不清楚。我們使用兩種纖毛蟲 （草履蟲和四膜蟲）以及小球藻，來研究內共生的早期發生過程。纖毛 蟲是一類古老而多樣的原生生物，在細胞生物學上具有許多與眾不同又 有趣的特徵。小球藻則是在生物科技工業中常被應用的材料，例如生質 能源的生產。利用纖毛蟲和小球藻，不但讓我們能夠研究內共生建立的 遺傳機制，也可以進一步探索其他細胞生物學以及生物科技工業相關的 問題。

2) 表現型穩定性的演化與分子機制

為什麼細胞可以在各種環境和遺傳背景下都保持一致的性能呢？儘管受 到外在環境和內在遺傳突變的干擾，都能保持穩定表現型的能力是生命 系統的基本屬性。長期以來，科學家一直相信細胞中含有主緩衝系統， 該系統可以在一般狀況下維持穩定的表現型，並在壓力下對其進行調 節。緩衝系統對於穩定環境和遺傳擾動下的細胞生理和發育過程至關重 要。此外，緩衝系統還可以調整演化的速度節奏，因為它們能夠緩和這 些變動，或幫助一個群體累積在天擇競爭下必要的遺傳變異。雖然遺傳和非遺傳緩衝效應的概念，已得到普遍的認可， 但是潛在的分子機制並不清楚。我們實驗室中將結合實驗演化和基因體組分析，用系統生物學方法探討這個問題。

• Education
• Achievements & Honors
• Selected publications
• Lab members

• PDF, 2000-2006, Dept. Dept. Mol. & Cell Biol., Harvard Univ., USA
• Ph.D., 1999, Dept. Mol. Cell, & Dev. Biol., Yale Univ., USA
• MS, 1990, Dept. Life Sciences, Natl. Tsing-Hua Univ.
• BS, 1988, Dept. Chemical Engineering, Natl. Tsing-Hua Univ.

• 2022, Ministry of Education Annual Academic Award (教育部學術獎)
• 2021, Ministry of Science and Technology Outstanding Research Award (科技部傑出研究獎)
• 2018, Outstanding Scholar Award, Foundation for the Advancement of Outstanding Scholarship (傑出人才發展基金會傑出人才講座)
• 2013, National Science Council Outstanding Research Award (國科會傑出研究獎)
• 2009, Academia Sinica Research Award for Junior Investigators in Taiwan, 2009 (中研院年輕學者著作獎)
• 2007, International Human Frontier Science Program (HFSP) Young Investigators’ Award (國際人類前沿科學計畫年輕研究學者獎)

1. Lee, H.-Y., Chou, J.-Y., Cheong, L., Chang, N.-H., Yang, S.-Y. and Leu, J.-Y. (2008) “Incompatibility of nuclear and mitochondrial genomes causes hybrid sterility between two yeast species.” Cell 135: 1065-1073.
2. Chou, J.-Y., Hung Y.-S., Lin, K.-H., Lee, H.-Y. and Leu, J.-Y.* “Multiple molecular mechanisms cause reproductive isolation between three yeast species.” PLoS Biology 8(7): e1000432 (2010).
3. Hsieh, Y.-Y., Hung, P.-H., Leu, J.-Y.* “Hsp90 regulates non-genetic variation in response to environmental stress.” Molecular Cell 50: 82-92 (2013).
4. Siegal, M.L.* and Leu, J.-Y.* “On the nature and evolutionary impact of phenotypic robustness mechanisms.” Annual Review of Ecology, Evolution, and Systematics 45: 495-517 (2014).
5. McDonald, M.J.*, Yu, Y.-H., Guo, J.-F., Chong, S.-Y., Kao, C.-F. and Leu, J.-Y.* “Mutation at a distance caused by homopolymeric guanine repeats in Saccharomyces cerevisiae.” Science Advances 2: e1501033 (2016).
6. You, S.-T., Jhou, Y.-T., Kao, C.-F. and Leu, J.-Y.* “Experimental evolution reveals a general role for the methyltransferase Hmt1 in noise buffering.” PLoS Biology 17(10): e3000433 (2019).
7. Leu, J.-Y., Chang, S.-L., Chao, J.-C., Woods, L.C. and McDonald, M.J.* “Sex alters molecular evolution in diploid experimental populations of S. cerevisiae.” Nature Ecology Evolution 4(3): 453-460 (2020).
8. Amine, A.A.A., Liao, C.-W., Hsu, P.-C., Opoc, F.J.G. and Leu, J.-Y.*, “Experimental evolution improves mitochondrial genome quality control in Saccharomyces cerevisiae and extends its replicative lifespan.” Current Biology 31(16): 3663-3670 (2021).
9. Swamy, K.B.S., Lee, H.-Y., Ladra, C., Liu, C.-F.J., Chao, J.-C., Chen, Y.-Y. and Leu, J.-Y.* “Proteotoxicity caused by perturbed protein complexes underlies hybrid incompatibility in yeast.” Nature Communications 13: 4394 (2022).
10. Lai, H.-Y., Yu, Y.-H., Jhou, Y.-T., Liao, C.-W. and Leu, J.-Y.* “Multiple intermolecular interactions facilitate rapid evolution of essential genes.” Nature Ecol. Evol. 7(5): 745-755 (2023).