# The gene regulatory basis of the genotype-phenotype map

> **NIH NIH R35** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $236,409

## Abstract

PROJECT SUMMARY
This research program seeks to reveal how morphological traits are genetically encoded during development
and modified during evolution. Gene regulatory networks are key to generating the physical features of an
organism, as they govern the spatial and temporal expression of each gene during its development. It is now
well accepted that phenotypic differences between species and within populations, including the human
population, are often caused by changes to regulatory networks which alter expression levels or timing.
Despite much progress in this field, our understanding of network function and evolution is lacking in several
major areas: (1) how do new traits emerge from changes to networks? (2) how do networks influence the
behavior of cells in developing tissues? (3) how do mutations that affect gene regulation permeate networks
and populations to cause traits? This research will leverage the highly tractable Drosophila melanogaster
model to answer these questions.
The first theme of this program will address a gene regulatory network controlling a rapidly evolving three-
dimensional anatomical structure in Drosophila. The network which patterns this structure will be dissected to
determine how individual components became integrated into the network. In parallel, the proposed studies will
trace the connections between these networks and the cellular processes that drive morphogenesis. Finally,
genetic changes which alter the three-dimensional shape of these structures will be identified. Performing
these studies will provide an unprecedented view of how gene regulatory networks are assembled and
modified to generate physical differences in tissue structure and produce elaborate morphologies.
The second theme comprises studies on Drosophila pigmentation traits that differ among populations and
between species. Most traits involve multiple loci, and much of this polygenic variation will be derived from
standing variants that persist in populations without phenotypic consequences. The accumulation of multiple
genetic changes will be traced and connected to a putatively adaptive pigmentation trait in Drosophila
melanogaster. The pigmentation trait under study is controlled by Hox transcription factors, which are highly
conserved body-patterning genes shared between flies and humans. This project will examine Hox gene
function and evolution in populations and between species to determine how the gene regulatory network for
this trait arose and diversified. This work will provide a deep molecular understanding of how phenotypes are
generated, informing the nature of these processes in less tractable systems, including humans.

## Key facts

- **NIH application ID:** 10206337
- **Project number:** 1R35GM141967-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Mark J Rebeiz
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $236,409
- **Award type:** 1
- **Project period:** 2021-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10206337

## Citation

> US National Institutes of Health, RePORTER application 10206337, The gene regulatory basis of the genotype-phenotype map (1R35GM141967-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10206337. Licensed CC0.

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