# Functional Analysis of the Anti-Müllerian Hormone as a Convergently Acquired Master Sex Determination Gene

> **NIH NIH R01** · UNIVERSITY OF GEORGIA · 2024 · $311,238

## Abstract

PROJECT SUMMARY
Development of separate sexes is a fundamental process throughout vertebrates. In many species, male and
female differentiation is triggered early during embryogenesis by a master sex determination (MSD) gene that
resides on the Y chromosome. Although sex differentiation is a remarkably conserved process among
vertebrates, the MSD gene that initiates the process is incredibly variable. It remains unclear how a diverse
assortment of MSD genes integrates with the canonical vertebrate sex differentiation network. A clear
understanding of the genetic regulation of sex determination and differentiation is essential because disruptions
in this process can lead to several disorders of sexual development. Our long-term goals are to use the diverse
types of sex chromosomes among closely related species of stickleback fish to determine how anti-Müllerian
hormone (Amh) has been repeatedly co-opted into a role as an MSD gene. Work in my lab has established
stickleback fish as a premier vertebrate model system to understand how sex chromosomes and sex
determination evolves. We have identified the independent acquisition of a Y-linked Amh (Amhy) in two species
of stickleback fish that evolved through separate duplications and translocations. Our central hypothesis is that
sex-linked copies of Amh (Amhy) can elicit a similar transcriptional response in the sex differentiation network
across species. This occurs once duplicates have independently gained regulatory elements necessary for
expression during early primordial gonad development. In this proposal we will use an innovative combination of
functional genetics and comparative genomics to explore our hypothesis through three aims: (1) Determine if
Amhy is necessary and sufficient for male development in threespine and brook stickleback fish, (2) Identify how
Amhy is regulated during the time of sex determination, and (3) Characterize how the downstream sex
differentiation regulatory network responds to the acquisition of Amhy as an MSD gene. This project will have a
significant impact on the field as it will reveal the genetic mechanisms responsible for the observed plasticity in
sex determination across vertebrates. This work will also lead to broader insights into the common function of
Amh across vertebrates as a whole and will provide key genomic resources that will further enable stickleback
fish as a leading vertebrate model system to understand how sex chromosomes evolve.

## Key facts

- **NIH application ID:** 10809729
- **Project number:** 5R01GM147312-02
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Michael Andrew White
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $311,238
- **Award type:** 5
- **Project period:** 2023-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10809729

## Citation

> US National Institutes of Health, RePORTER application 10809729, Functional Analysis of the Anti-Müllerian Hormone as a Convergently Acquired Master Sex Determination Gene (5R01GM147312-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10809729. Licensed CC0.

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