# Evolution of gene regulation through overlapping regulatory mechanisms

> **NIH NIH R01** · CORNELL UNIVERSITY · 2020 · $328,026

## Abstract

PROJECT SUMMARY
 It is increasingly clear that the evolution of gene regulation plays an important role in
determining morphological, behavioral and physiological diversity between and within species.
Understanding the evolutionary mode of gene regulation is critical for expanding fundamental
knowledge about living systems. Although it is well known that gene regulation is an intricate
process that can occur at multiple levels, the question remains to as to how gene regulation has
evolved at these levels leading to the same regulatory consequences. It is also important to
illustrate whether and how phenotypically robust regulation of the same orthologous genes in
different species can be achieved using different mechanisms. The latter issue is particularly
pivotal in addressing how robustness in gene regulation evolved in nature.
 Yeasts provide unique model systems to study the evolution of gene regulation because
of the advanced knowledge on their biology and exceptionally powerful genetics and genomics
tools. With ample glucose and sufficient oxygen, most eukaryotic organisms catabolize glucose
via mitochondrial respiration. In contrast, baker's yeast, Saccharomyces cerevisiae, and its
close relatives, have evolved to conduct fermentation even in the presence of oxygen (aerobic
fermentation) after whole genome duplication (WGD). Regulation of mitochondrial functions
plays a critical role in aerobic fermentation. Hundreds of nuclear genes that function in
mitochondria have evolved to be repressed by glucose only in the post-WGD yeast species
through several regulatory mechanisms. Our aim is to use yeasts as models to elucidate how
these novel gene regulatory mechanisms evolved. To continue our previous contribution on
functional redundancy and evolution, we will further establish a novel conceptual framework for
gene regulation evolution that can be readily tested in other research systems, i.e. the same
orthologous genes could achieve robust regulation in different species by evolutionary drift
among functionally overlapping mechanisms.
 New knowledge that can be learned uniquely from the proposed studies will lead to a
much broader appreciation for the importance of gene regulatory evolution. This research can
also reveal new insights into regulatory changes of mitochondrial functions in cancers, due to
the metabolic similarity between yeasts and tumor cells. We believe that even though this
application is specific to an inherent phenomenon in yeast, it asks general questions about the
evolution of gene regulation, and thus will have a significant impact on evolutionary and medical
research.

## Key facts

- **NIH application ID:** 9989863
- **Project number:** 5R01GM117190-04
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Zhenglong Gu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $328,026
- **Award type:** 5
- **Project period:** 2017-09-15 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989863

## Citation

> US National Institutes of Health, RePORTER application 9989863, Evolution of gene regulation through overlapping regulatory mechanisms (5R01GM117190-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9989863. Licensed CC0.

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