# Genomic and physiological impact of transposable elements

> **NIH NIH R35** · CORNELL UNIVERSITY · 2020 · $507,738

## Abstract

PROJECT SUMMARY
Transposable elements (TEs) make up more than half of the human genome, and their transposition and
rearrangement have been directly implicated in causing more than 100 genetic diseases. Because of
these mutagenic properties, TEs are important drivers of genetic variation between and within species.
TE activity accounts for most of the DNA that is unique to each mammal species, and is responsible for
as much as 30% of structural genomic variation within the human population. However how this
enormous source of genetic variation impacts the evolution and physiology of species remains poorly
understood. This project is designed to yield transformative insights into the biological significance of TEs
in evolution and disease. The central hypothesis tested in this proposal is that prefabricated regulatory
and coding activities ancestrally encoded by TEs have been co-opted repeatedly during vertebrate
evolution to promote the emergence of new cellular functions. At the regulatory level, we will deploy
innovative computational and experimental approaches to test the hypothesis that polymorphic and
lineage-specific TEs make a substantial contribution to transcriptomic and cis-regulatory variation within
humans and across a diverse set of mammal species, including primates, rodents and bats, with an
emphasis on the origin and turnover of long noncoding RNA repertoires. Furthermore, we will investigate
the role of TEs in the regulatory evolution of a major component of the innate immune system, the
interferon response. Experimental manipulations in cell lines, including genome editing and functional
assays, will be used to validate the functional significance of TE-derived regulatory sequences. At the
protein-coding level, we will combine evolutionary sequence analysis and functional assays to
characterize several TE-derived genes co-opted for cellular function in the human genome. Notably we
will test the hypothesis that envelope proteins derived from endogenous retroviruses are capable of
protecting cells from retroviral infection. We will also investigate several domesticated transposases
involved in brain function and development. Together the outcomes of this proposal are anticipated to
shift the perception of TEs from inert molecular fossils to active contributors to the evolutionary plasticity
of vertebrate genomes. In addition, our studies are bound to reveal crucial new insights into the role of
mobile genetic elements in promoting disease states, including cancer, autoimmunity, and
neurodevelopmental disorders.

## Key facts

- **NIH application ID:** 9989172
- **Project number:** 5R35GM122550-04
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Cedric Feschotte
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $507,738
- **Award type:** 5
- **Project period:** 2017-09-08 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989172

## Citation

> US National Institutes of Health, RePORTER application 9989172, Genomic and physiological impact of transposable elements (5R35GM122550-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9989172. Licensed CC0.

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