# Gene duplication and divergence:  the bigger picture

> **NIH NIH R01** · UNIVERSITY OF COLORADO · 2020 · $349,046

## Abstract

Gene duplication and divergence has driven evolutionary innovation in all domains of life. We have learned
a great deal from previous bioinformatic, genetic and biochemical investigations that focused on mutations in
duplicated genes. However, these approaches miss an important biological reality – the context in which a newly
duplicated gene is evolving. Mutations elsewhere in the genome that improve fitness in the face of an
evolutionary challenge may be just as important as mutations in the gene undergoing divergence. Such
mutations may rewire metabolic or regulatory networks in ways that boost fitness in the short run, but may
sacrifice a previously well-evolved function in the process. We term these “expedient” mutations. Expedient
mutations and mutations in duplicated genes are inextricably intertwined as organisms evolve new genes.
 We will investigate the role of expedient mutations during evolution of a new protein using a model system
in which that novel protein is required for growth. ∆argC E. coli cannot synthesize arginine. A point mutation
allows E383A ProA (ProA*) to catalyze both its native reaction and the ArgC reaction, albeit poorly. We evolved
∆argC proA* E. coli on glucose + proline (conditions in which there is selection only for improved arginine
synthesis). Growth rate is improved by amplification of proA*, a mutation that improves the ability of ProA* to
catalyze the ArgC reaction, as well as expedient mutations that enhance arginine synthesis by other
mechanisms. We will use our ∆argC proA* model system to address three aspects of gene duplication and
divergence certain to have played a major role in expanding the capabilities of organisms, shaping their
genomes, and determining which lineages win and which lose when environmental conditions change.
 In Aim 1, we will determine which expedient mutations that arose during evolution of the ∆argC proA* strain
on glucose + proline are detrimental after an efficient replacement for ArgC has evolved, and how they can be
repaired. In Aim 2, we will investigate how expedient mutations enhance fitness in the more complex situation
when both the original and novel functions of ProA* are required. Finally, in Aim 3, we will address how genome
content, gene context and sequence differences between orthologs affect the process of evolution of a
replacement for ArgC in four different bacterial species.
 This work will answer important questions about how new genes have evolved throughout the history of life
and in the present due to new selective pressures imposed by anthropogenic pharmaceuticals and pesticides.
We will gain a better understanding of the interplay between mutations in a new gene encoding a weak-link
enzyme and mutations in the rest of the genome. We will establish what kinds of collateral damage are caused
by expedient mutations, and how those expedient mutations are themselves accommodated. Finally, we will
gain insight into how differences in microbial genomes affec...

## Key facts

- **NIH application ID:** 9990831
- **Project number:** 5R01GM134044-02
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** SHELLEY D. COPLEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $349,046
- **Award type:** 5
- **Project period:** 2019-08-12 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9990831

## Citation

> US National Institutes of Health, RePORTER application 9990831, Gene duplication and divergence:  the bigger picture (5R01GM134044-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9990831. Licensed CC0.

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