Evolutionary Epigenetics lab

population genetics, chromatin biology, transposable elements

About us

The Lee lab is part of the Ecology and Evolutionary Biology at the University of California, Irvine.

Genetic variation is the ultimate determinant of the myriad diversity of life and our health. We study the molecular and cellular mechanisms shaping genetic variation and genome evolution. We currently focus on the evolution of a widespread genomic parasite, “transposable elements” (TEs), who can copy themselves and move to new genomic locations. TEs are important contributors to phenotypic variation, including disease states, in natural populations. We study the intimate evolutionary relationships between TEs and host genomes through investigating TEs’ functional impacts and population dynamics. We use Drosophila (fruit flies hovering over fruits!!) as a model system, and combine population genomics, epigenomics, bioinformatics, and cell biology.

In addition to TEs, we study the evolution of non-repetitive sequences, in particular protein-coding genes. We investigate how internal cellular and molecular processes, such as 3D organization of the genome and the antagonistic interaction between hosts and genetic parasites, determine genetic variation and shape genome evolution.

Epigenetic effects of transposable elements along linear chromosomes

Organisms have evolved ways to “mark” TE sequences with repressive epigenetic marks, which reduce the ability of TEs to move and to multiply. However, these repressive epigenetic marks at TEs inadvertently “spread” to neighboring genes along the linear chromosome. We found that this phenomenon (“epigenetic effects of TEs”) is prevalent across Drosophila genomes (as well as in other animal and plant species!), interferes with gene function, and impairs hosts’ fitness. In other words, TEs are deleterious because of host silencing mechanisms evolved to reduce TEs’ harmful effects. We are investigating why organisms failed to curb these harmful side effects and studying the associated functional consequences on the evolution of both host genomes and TEs.

Epigenetic effects of transposable elements in 3D nuclear space

In addition to exerting epigenetic effects along the linear chromosomes, we found that epigenetically silenced TEs can have epigenetic effects in 3D nuclear space. TEs interact with distant “dark matter” of the genome (“heterochromatin”) through “liquid-liquid phase separation” (just like the separation of oil and vinegar in salad dressing!). These 3D epigenetic effects of TEs can mislocalize genomic regions in 3D nuclear space, changing the overall genome organization. We are investigating how TE-mediated nuclear reposition of various genomic regions influence cellular functions, and how this influence genome evolution.

Population genomics of transposable elements

While TEs have been found in virtually all eukaryotic genomes surveyed, there is substantial variation in their abundance, composition, and genomic positions within and between species. For instance, TEs occupy less than 1% of the honeybee genome, but ~45% of the human genome and more than 85% of some plant genomes. Using comparative population genomics and theoretical modeling, we are investigating the evolutionary forces driving this remarkable difference in TEs’ evolutionary dynamics between species.

Evolutionary genomics of coding sequences

We have a continuing interest in understanding the evolution of protein-coding genes. Our previous work demonstrates that not only external environmental factors, but also internal genetic processes influence genetic variation. We are investigating how cellular epigenetic environment influences key evolutionary forces that determine genetic variation and genome evolution, including mutation and recombination.

Current Members

Grace Yuh Chwen Lee - PI

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    • Grace received her Ph.D. from UC Davis with Charles Langley on population genetics. She did postdocs with Manyuan Long at the University of Chicago on evolutionary genetics and with Gary Karpen at the Lawrence Berkeley National Lab on epigenetics and chromosome biology. Grace joined the faculty at the UC Irvine as an Assistant Professor of Ecology and Evolutionary Biology in July 2019.

    Grace has been a big fan of transposable elements, and she loves the beauty of tiny fruit flies. When not playing with flies or computers, Grace is usually going for a walk with Purin (named after this character), a 15-year young Yorkie rescue (senior dogs rock!!). She is also an avid classical music lover and enjoys reading about food.

    Yuheng Huang - postdoc

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    Yuheng did his Ph.D. at U. Toronto with Aneil Agrawal, where he used experimental fly populations to study the effects of varying environments on genetic variation, adaptability, and transcriptomic plasticity. He did a postdoc at UW-Madison with John Pool, where he studied the genomic and transcriptomic basis of adaptation to cold environments in natural fly populations. Currently, Yuheng is studying the interplay between epigenetics and the evolution of gene regulation.
    Fruit fly is Yuheng's favorite model organism. Its easiness to keep in the lab, short generation time, and a wide range of genetic resources allow him to experimentally study interesting evolutionary genetic questions. Outside the lab, Yuheng enjoys reading, jogging, and playing table tennis.

    Imtiyaz Hariyani - PhD student

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    Imtiyaz is a second-year PhD student in the EEB department. His interests lie in the transcriptome, and he is particularly intrigued by transposable elements. Prior to joining UCI, Imtiyaz completed his undergraduate degree in Biology at NYU Abu Dhabi and later worked as a bioinformatician with Stephane Boissinot at NYUAD. In his free time, Imtiyaz enjoys being out in nature and taking walks along the coast. He is also a huge cricket fan and is excited about a new cricket stadium being built in Irvine, CA! Imtiyaz enjoys reading and chatting about life, religion, and philosophy, so feel free to connect with him at any time!

    Zita Gao - Junior Specialist

    Coming soon!

    Jennifer McIntyre - undergraduate researcher

    Majoring in Biology, Jenny is a third year student at Scripps College. She is intrigued by epigenetics and is excited about the interdisciplinary nature of bioinformatics. In her free time, she enjoys doing crafts, listening to music, and spending time with her friends and family (and her cat Tigger!). Jenny was recently awarded an undergrad travel award and poster presentation award from the Genetics Society of America for her work on the enviornmental impacts on transposable elements.

    Leila H. Lin - undergraduate researcher

    Leila is a junior majoring in Biological Sciences at UC Irvine and is aiming to pursue research as a career. She has always been curious about the inner mechanisms of the world and loves to try and explain everything she observes. The introduction of CRISPR and previous experience with Drosophila in genetics research has greatly influenced her interest in anything related to the human genome. Outside of STEM subjects, she loves art, photography and really wants to try ceramics. Leila was recently awarded the Excellence in Research Award and Howard Schneiderman Prize from UCI Biological Sciences for her work on the evolution of heterochromatin genes.

    Nicole Quinteros - undergraduate student

    Nicole is a third year Biological Sciences Major at UC Irvine, hoping to pursue a career in medicine or research. The research of her past professors has peaked her interest in epigenomics and evolutionary biology. She enjoys exploring how the fields work together and affect the fitness of various species. Outside of the lab, she enjoys working as an EMT, painting, doing word searches, and attempting to bake.

    Marquel G. Huston - undergraduate researcher

    Marquel graduated from UC Irvine in 2022 with a degree in Biological Sciences, and a minor in Medical Anthropology. She is pursuing a career in the medial field, and aims to improve the healthcare industry while simultaneously focusing on the wellbeing of others. She was extremely intrigued by selfish DNA after she had taken professor Lee’s class and thus wanted to continue to learn and explore by doing research. She was very interested by the link between transposable elements and various human diseases. Outside of school and work Marquel enjoys hanging out with her friends at Disneyland and spending time with her cats - Ida Claire, Dublin, and Bernadette.

    Joana Romero - undergraduate student

    Joana is a fourth year biological sciences major at UC Irvine. In the future, she hopes to be a part of a research and development department under a biotech company. Joana has always been interested in epigenetics and genetic engineering. Apart from her pursuit for scientific knowledge, she is also fond of music and literature and is working on improving her cooking skills.

    Kayla Ly - undergraduate student

    coming soon!

    David Kim - high school student

    David is currently a sophomore attending Portola High School. He is greatly interested in biology and is intrigued by the interrelation of multiple scientific fields. David is very excited about his first upcoming presentation on the evolution of mammalian DNA repair genes at a student research conference hosted by Sigma Xi! In his free time, David enjoys playing sports, learning new skills, and spending time with his friends and family.

    Alumni

    Harsh Shukla (MCSB rotation student) - Harsh is now at J.J. Emerson lab and remains in close collaboration with us.
    Lauren Huang (UCLA undergraduate student) - Lauren is applying for medschool to fulfill her passion of helping others.
    Andy Nguyen (UC LEADS summer student) - Andy is now a grad student at UPenn.
    Jasmine Osei-Enin (Junior specialist) - Jasmine is pursuing her passion for science policy.
    Kha Bao (Bio 199 undergraduate student; UROP awardee)
    Nikitha Vancheeswaran (Bio 199 undergraduate student)
    Maya Louis (Bio 199 undergraduate student)

    YOU?

Join the lab

We are actively looking for enthusiastic postdocs and students to join us!
Postdocs - If you are looking for a postdoc and find that our research interests align, please send Grace your CV, name of three references, and a one-page (max) description of your research experience and interests and you as a person.

Graduate students - For prospective graduate students, we are part of the graduate program of the Department of Ecology and Evolutionary Biology, the Mathematical, Computational, and Systems Biology (MCSB) Gateway program, and the Genetics, Epigenetics, and Genomics (GEG) graduate program. If you are interested in joinning the lab as a graduate student, please send Grace your CV and reserach interest, so we can discuss which graduate program may be the best to apply to.

Undergraduate students - We welcome dedicated and motivated undergraduate students to join us. Please send Grace a short description of why you would like to join the lab, your backgroud in science (biology/math/computer science etc), and you generally as a person.



Publications

publication at UC Irvine
  • Huang, Y.H., H.G. Shukla and Y.C.G. Lee. (2022)
    Host chromatin environment shapes the evolutionary dynamics of transposable elements.
    in press in eLife. preprint atlink
  • Y.C.G. Lee. (2022)
    Synergistic epistasis of the deleterious effects of transposable elements.
    Genetics 220(2), iyab211. Issue Highlight link
  • Choi, J.C. and Y.C.G. Lee. (2020)
    Double-edged sword: the evolutionary consequences of the epigenetic silencing of transposable elements.
    PLoS Genetics 16(7): e1008872. Cover story link
publication before UC Irvine
  • Lee, Y.C.G., Y. Ogiyama, D. Acevedo, N.C. Martins, B.J. Beliveau, C.T. Wu, G. Cavalli, and G.H. Karpen. (2020)
    Pericentromeric heterochromatin is hierarchically organized and spatially contacts H3K9me2/3 islands located in euchromatic genome.
    PLoS Genetics 16(3): e1008673. link
  • Mills, W.K., Y.C.G. Lee, A.M. Kochendoerfer, E.M. Dunleavy, and G.H. Karpen. (2019)
    RNA transcribed from heterochromatic simple-tandem repeats are required for male fertility and histone-protamine exchange in Drosophila melanogaster.
    eLife 8:e48940. link
  • Lee, Y.C.G., I.M. Ventura, G.R. Rice, D.Y. Chen, and M. Long. (2019)
    Rapid evolution of gained essential developmental functions of a young gene via interactions with other essential genes.
    Molecular Biology and Evolution 36 (10), 2212-2226. link
  • Lee, Y.C.G. and M.T. Levine. (2017)
    Germline genome protection on an evolutionary treadmill.
    Developmental Cell 43(1): 1-3. link
  • Lee, Y.C.G. and G.H. Karpen. (2017)
    Pervasive epigenetic effects of euchromatic transposable elements that shape their own evolution.
    eLife 6:e25762. recommended by F1000 link
  • Lee, Y.C.G., Q. Yang, W. Chi, W. Du, S.A. Turkson, C. Kemkemer, Z.Z. Zheng, X. Zhuang, and M. Long. (2017)
    Genetic architecture of adult foraging behavior that is essential for the survival of Drosophila melanogaster.
    Genome Biology and Evolution 9 (5): 1357-1369. link
  • Turissini, D.A., A.A. Comeault, G. Liu, Y.C.G. Lee, and D.R. Matute. (2017)
    Drosophila hybrids have troubles finding food. Evolution 71-4:960-973. link
  • Lee, Y.C.G., C. Leek, and M.T. Levine. (2017)
    Recurrent innovation at genes required for telomere integrity in Drosophila. Molecular Biology and Evolution 34 (2): 467-482. link
  • Lee, Y.C.G. (2015)
    The role of piRNA-mediated epigenetic silencing in the population dynamics of transposable elements in Drosophila melanogaster. PLoS Genetics 11(6): e1005269. link
  • Lee, Y.C.G., C.H. Langley and D.J. Begun (2014)
    Differential strengths of positive selection revealed by hitchhiking effects at small physical scales in Drosophila melanogaster. Molecular Biology and Evolution 31(4): 804-816. link
  • Lee, Y.C.G.* and H.H. Chang* (2013)
    The evolution and functional significance of nested gene structures in Drosophila melanogaster. Genome Biology and Evolution 5(10):1978-1985. link
  • Lee, Y.C.G. and C.H. Langley (2012)
    Long-term and short-term evolutionary impacts of transposable elements on Drosophila. Genetics 192(4):1411-32. Issue Highlight. link
  • Langley, C.H., K. Steven, C.M. Cardeno, Y.C.G. Lee, D.R. Schrider, J.E. Pool, S.A. Langley, C. Suarez, R. Detig-Corbet, B. Kolaczkowski, S. Fang, P.M. Nista, A.K. Holloway, A.D. Kern, C.N. Dewey, Y.S. Song, M.W. Hahn and D.J. Begun (2012)
    Genomic variation in natural populations of Drosophila melanogaster. Genetics 192(2):533-98. Issue Highlight. link
  • Levine, M.T., C. McCoy, D. Vermaak, Y.C.G. Lee, M.A. Hiatt, F.A. Matsen and H.S. Malik (2012)
    Phylogenomic analysis reveals dynamic evolutionary history of the Drosophila heterochromatin protein 1 (HP1) gene family. PLoS Genetics 8(6): e1002729. link
  • Lee, Y.C.G.* and J.A. Reinhardt* (2012)
    Widespread polymorphism in the positions of stop codons in Drosophila melanogaster. Genome Biology and Evolution 4(4):533-49. link
  • Lee, Y.C.G. and C.H. Langley (2010)
    Transposable elements in natural populations of Drosophila melanogaster. Philosophical Transactions of the Royal Society B 365: 1219-1228. link
*equal contribution

Contact

5323 McGaugh Hall, UC Irvine
(949) 824-0615