Evolutionary Epigenetics lab

population genetics, genomics, chromatin biology, transposable elements

About us

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

We study the molecular and cellular mechanisms shaping genome variation, which is the ultimate determinant of the myriad diversity of life and our health. Our current work focuses on a substantial component of most eukaryotic genomes, "transposable elements" (TEs), which copy themselves and move to new genomic locations. We aim to understand how these widespread and variable "genomic parasites" shape the evolution of genomes through altering chromatin landscapes. To achieve this, we use Drosophila (fruit flies hovering over fruits!!) as a model system, and integrate population genomics, epigenomics, computational biology, and cell biology.

In addition to TEs, we investgiate the variation of chromatin landscapes within and between species and identify the functional causes and evolutionary consequences of such variation.

Epigenetic effects of transposable elements along linear chromosomes

Various eukaryotes have evolved ways to “mark” TE sequences with repressive epigenetic marks, which reduce the ability of TEs to move and to multiply. However, we and others discovered that these repressive epigenetic marks at TEs inadvertently “spread” to neighboring genes along the linear chromosome in insects, plants, and mammals. Our recent results further revealed that this phenomenon (“epigenetic effects of TEs”) is prevalent across the Drosophila genomes, interferes with gene function, and impairs organismal 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 eukaryotic 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. By combining functional genomics and cytology, we discovered that 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 spatial interactions can mislocalize genomic regions in 3D nuclear space, altering genome organization. We are investigating how TE-mediated nuclear reposition of various genomic regions influences cellular functions, and how this shapes 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 using both comparative functional genomics and theoretical modeling.

Roles of chromatin landscape in shaping genome evolution

Chromatin modifications (either at DNA or at histones wrapped by DNA) could influence fundamental cellular processes, including transcription, DNA repair, and, of course, regulations of our favorite genetic elements, TEs. Our recent studies reveal that the chromatin landscape is quite variable between even closely related species. We are investigating how such variation contributes to differing cellular processes and thus genome evolution. We also aim to unearth how and why the chromatin landscapes differ between species at the first place.

Current Members

Grace Yuh Chwen Lee - PI

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    • Grace received her B.S. in Life Sciences from National Taiwan University and 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 is an Assistant Professor of Ecology and Evolutionary Biology and Center for Complex Biological Systems and at UC Irvine. 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 16-year young Yorkie rescue (senior dogs rock!!). She is also an avid classical music lover, and enjoys reading about food and (re)watching works by Studio Ghibli. She hopes to learn Japanese one day.

    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.

    Zita Gao - graduate student

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    Zita is a first year graduate student in EEB. She received her B.S from UC Davis with a major in Genetics and Genomics and a minor in Ecology, Evolution and Biodiversity. Before joining UCI, she did undergraduate research with Joanna Chiu at UCD, where she studied circadian rhythm and insecticide resistance in Drosophila. Inspired by prior research and bioinformatics experiences, she is interested in how the non-coding region of the genome, particularly transposable elements, play roles in evolution and genome landscape across different species. Outside of lab, she enjoys swimming, exploring waterfalls and building legos.

    Harsh Shukla - graduate student (with Emerson lab)

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    ZHarsh completed his bachelors 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. Harsh has come to love the model organism fruit fly. Currently he is working on the project that is looking at how TEs may rewire the Drosophila 3D genomes by developing new methods. Outside the lab, Harsh loves to travel and backpack. He adores reading; biking/cycling is his go to stress buster.

    Leila H. Lin - lab manager

    Leila is a recent graduate from the 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. Leila was awarded the Excellence in Research Award and Howard Schneiderman Prize from UCI Biological Sciences for her work on the evolution of heterochromatin genes. She also received the Victoria Finnerty Award and a poster award from the Genetics Society of America. Outside of STEM subjects, she loves art, photography and really wants to try ceramics.

    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. Jenny was recently awarded an undergrad travel award and a poster presentation award from the Genetics Society of America for her work on the enviornmental impacts on transposable elements. In her free time, she enjoys doing crafts, listening to music, and spending time with her friends and family (and her cat Tigger!).

    Kayla Ly - undergraduate student

    Kayla is a third year Human Biology major at UC Irvine. She hopes to one day pursue a career in optometry. After careful consideration of various research labs, Evolutionary Epigenetics lab's work on transposable elements piqued her interest the most and did not disappoint! As of now, she is most interested in the effect transposable elements might have on recombination in DNA. Kayla was recently awarded both the Distinguished Research Fellowship and Summer Research Fellowship from UCI to perform genetic mapping on factors influencing transposable elements. Outside of school and work, Kayla spends her time reading and managing her studygram account.

    Hannah Lee - undergraduate student

    Hannah is first year biological science major with an interest in minoring in anthropology. She is extremely intrigued with TEs (especially because not much is known about them!) and is curious about their effects on fertility and diseases. Hannah is awarded a Summer Research Fellowship from UCI to investigate genetic factors shaping transposable elements. Outside of the lab she enjoys playing violin or spending time with her cat Mijah.

    Alumni

    David Kim (high school student) - David is attending Harvard University this upcoming summer!
    Nicole Quinteros (Bio 199 undergraduate student; UROP awardee) - Nicole is pursuing her goal of being a PA.
    Joana Romero (Bio 199 undergraduate student; UROP awardee) - Joana is now a lab tech in a toxicology lab.
    Marquel G. Huston (Bio 199 undergraduate student) - Marquel is attending PA school.
    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

publications at UC Irvine publications 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. 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