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 14-year young Yorkie rescue (senior dogs rock!!). She is also an avid classical music lover and enjoys going to concerts (during pandemic, here is her solution).

    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.

    Nicolas Burghgraeve - postdoc (starting March 2021)

    Nicolas did his Ph.D. at Université de Lille in France with Vincent Castric. He studied the evolution of the self-incompatibility locus in the plant genus Arabidopsis, focusing on the dominance relationship between alleles and the evolutionary consequences of balancing selection. He has now jumped into the wonderful world of fruit flies and appreciates all the great possibilities offered by this tiny model organism to study evolutionary genetics.

    Nicolas likes cultural events (e.g., museum’s new exhibitions, live concerts) and sport/outside activities (he especially likes hiking and traveling). He also enjoys cooking (always curious to try new recipes), reading a book, and playing games with his friends.

    Harsh Shukla - MCSB rotation student

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    Harsh completed his bachelor in computer science from Nirma University, India. Getting interested in biology during his final undergrad project, he went on to pursue his masters in Bioinformatics at IBAB, Bangalore. For his master's thesis, he worked on improving the human reference genome by leveraging population-level information. After completing his masters, Harsh worked on Conservation Genomics in Dr.Uma Ramakrishnan's lab at NCBS, Bangalore, for a year.

    Harsh joined the MCSB program in Fall 2019 at UCI. He is primarily interested in the field of evolutionary and population genomics, and has come to love the model organism fruit fly. Currently, he is working on the evolutionary impacts of TEs' epigenetic effects and is developing a pipeline that estimates TE frequency spectra in natural populations. Outside the lab, Harsh loves to travel and backpack. He adores reading; biking/cycling is his go-to stress buster.

    Maya Louis - undergraduate student

    Maya is a senior at UC Irvine, pursuing a major in Biological Sciences and a minor in Sociology. She is intrigued by epigenetics and how it regulates the genomes of different species. Outside of academics, Maya enjoys listening to music, reading old romance novels, walking on the beach, and trying new foods with friends.

    Lauren Huang - undergraduate student

    Lauren is currently in her third year at UCLA, majoring in Human Biology and Society and minoring in Applied Developmental Psychology. She worked as an undergraduate researcher for the Human Connectome Project led by Dr. Susan Bookheimer, where she helped accumulate a compilation of neural data on the human brain. She is interested in studying epigenetic effects on Drosophila species and how that can be applied to the human population. Lauren enjoys exploring new places to eat, traveling (when there isn't a pandemic going on), and learning new languages.

    Jennifer McIntyre - undergraduate student

    Majoring in Biology, Jennifer is a first 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.

    Leila H. Lin - undergraduate student

    Leila is a freshman 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.

    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.

    Andy Nguyen - UC LEADS summer student (UCLA, summer 2020)

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Join the lab

Open position: Junior/Assistant Specialist in Evolutionary Epigenomics Lab

We are 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 and a one-page description of your research interest and career goal.

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

  • 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
  • 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