# Causes of excess expression of tandem duplicate genes

> **NIH NIH R15** · WILLIAMS COLLEGE · 2020 · $401,846

## Abstract

PROJECT SUMMARY
Tandem duplicate genes are a core part of human genome structure. At the same time,
variations in gene copy number occur frequently in humans, leading to diseases such as autism,
schizophrenia, and bleeding disorders, as well as variation in individual traits. Despite this
growing relevance, biologists have a limited understanding of the direct effects of tandem gene
duplication.
A simple prediction is that a tandem duplication of an entire gene would double gene
expression. Instead, recent studies have found that young tandem duplicate genes are more
than twice as active as single copy genes, producing an excess of RNA and protein over the
expected 2-fold level. The tandem structure of the gene is responsible for the excess, not the
change in copy number, suggesting that gene proximity and/or specific regulatory sequences
may be responsible. Population-level studies indicate that such large changes in gene
expression from tandem duplicates are often highly detrimental. However, despite the obvious
relevance for cellular and organismal function, it is not clear how this excess occurs and if it is
dependent on a specific aspect of gene structure.
The purpose of this proposal is to identify genetic factors that cause excess expression from
tandem duplicate genes. Aim 1 will test the hypothesis that divergence between duplicate gene
copies does not eliminate excess expression. Aim 2 will test the hypothesis that the excess
expression of tandem duplicates is distance-dependent, as predicted by a computer simulation
of gene transcription. Aim 3 will test the hypothesis that the excess expression is mediated by
insulator sequences, genetic factors with roles in other kinds of neighbor interactions. To pursue
these aims, a team primarily composed of undergraduate students will apply innovative gene-
construction techniques and precise quantitative expression assays in Drosophila flies to
provide new insight into how tandem genes work.

## Key facts

- **NIH application ID:** 10114381
- **Project number:** 1R15GM140429-01
- **Recipient organization:** WILLIAMS COLLEGE
- **Principal Investigator:** David Walker Loehlin
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $401,846
- **Award type:** 1
- **Project period:** 2020-09-15 → 2024-09-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10114381

## Citation

> US National Institutes of Health, RePORTER application 10114381, Causes of excess expression of tandem duplicate genes (1R15GM140429-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10114381. Licensed CC0.

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