# How transposable elements drive genome evolution through epigenetic mechanisms

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA-IRVINE · 2023 · $14,477

## Abstract

PROJECT SUMMARY
Transposable elements (TEs) are genomic parasites that can negatively impact host viability and fertility. They
have been identified as the causes of inherited human disorders and cancers. Despite their detrimental effects,
TEs are prevalent across eukaryotic genomes and exhibit dramatic variation in abundance and genomic
positions within and between species. For instance, the proportion of vertebrate genomes occupied by TEs
ranges from only 6% in pufferfish to 65% in salamander. Over 45% of the human genome harbors TEs, and
any two people differ by at least a thousand TE insertions. However, it remains unclear what evolutionary
forces drive TE variation and how that influences functions and, thereby, host health. Most studies of the
harmful effects of TEs have centered on TE-mediated physical disruption of DNA and changes in DNA
sequences. While such genetic disturbances have important consequences, this paradigm overlooks the
detrimental epigenetic effects mediated by TEs, including biochemical modifications of chromatin and
reorganization of three-dimensional (3D) genome structures. My recent pioneering studies revealed, on a
genome-wide scale, that epigenetically silenced TEs can perturb the function of neighboring genes through cis
spreading of silencing marks (cis epigenetic effects of TEs) and alter 3D genome organization (3D epigenetic
effects of TEs). These exciting observations offer a possibility to answer long-unresolved questions about why
there are between-species differences in TE content and how these differences affect genome function and
evolution—the overarching goals of my research program. My laboratory uses Drosophila as a primary model
and integrates evolutionary genomics and cell biology to decipher the functional and evolutionary significance
of TE variation. One major goal of my research program is to determine how TE variation influences genome
evolution through my newly discovered 3D epigenetic effects of TEs. My research group will use integrative
genomic analysis at multiple levels (DNA, RNA, epigenetics, and 3D genome structures) to investigate our
hypothesis that the 3D epigenetic effects mediated by TEs can produce varying 3D genome organization. We
further predict that this TE-mediated variation in 3D genome structures can shape genome evolution by
affecting fundamental genetic processes. In addition, my laboratory seeks to identify the molecular and
evolutionary mechanisms contributing to between-species differences in TE content. We will use Drosophila
genetics and transgenics to identify host genetic factors that modulate the epigenetic effects of TEs in cis and
in 3D nuclear space. Furthermore, we will combine comparative evolutionary genomics and experimental
evolution to investigate our hypothesis that between-species variation in these host genetic factors contributes
to varying epigenetic effects of TEs and ultimately drives the evolution of divergent TE content across
Drosophila species. ...

## Key facts

- **NIH application ID:** 10796187
- **Project number:** 3R35GM142494-02S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Grace Yuh Chwen Lee
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $14,477
- **Award type:** 3
- **Project period:** 2021-09-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10796187

## Citation

> US National Institutes of Health, RePORTER application 10796187, How transposable elements drive genome evolution through epigenetic mechanisms (3R35GM142494-02S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10796187. Licensed CC0.

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