# EDGE CMT: Genomic characterization of mammalian adaptation to frugivory

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $368,385

## Abstract

PROJECT SUMMARY
Overview:
A comprehensive molecular understanding of how mammals ascertain complex traits to adapt to specific
environments remains largely unknown. Here, we will take advantage of comparative and functional genomics
to systematically dissect dietary adaptation in mammals using frugivory as a model. Mammals evolved from a
common dietary ancestor to have an extremely broad range of diets. Amongst these, frugivorous adaptation is
of particular significance, as fruit-eating arose in multiple lineages within primate and bat orders. Frugivorous
adaptation is also of general interest as diets rich in sugar increase risk for diabetes and metabolic disease in
many mammals, including humans. Conversely, frugivorous primates and bats can eat large quantities of
fruit/sugar without apparent disease consequences. Supported by recent advances in genome availability and
genomic technologies, we plan to take a systematic approach to uncover frugivorous molecular factors by: 1)
carrying out comparative genomic analyses of primates and bats to identify sequences that were specifically
accelerated in frugivorous species combined with a wide-range of genomic techniques, including RNA-seq,
ATAC-seq, ChIP-seq and combined single-cell RNA-seq and ATAC-seq on metabolically pertinent insect and
fruit bat tissues; and 2) functionally validate frugivory-associated sequences using cell-based gene assays,
massively parallel reporter assays (MPRAs) and swapping these sequences into mice. Our work will
comprehensively identify the molecular components leading to frugivory and functionally characterize the
genes, regulatory elements and pathways involved in this complex trait.
Intellectual Merit:
As bats and primates encompass broad dietary ranges, and the evolutionary distances within each order are
sufficiently small, they offer ideal models for comparison within each group and between groups to analyze the
genetic determinants of dietary specializations. In addition, the use of mouse genetic engineering can allow for
functional validation of genetic candidates. We plan to not only identify protein changes that lead to phenotypic
differences but also gene regulatory elements that have been shown to be important drivers of morphological
change and the evolution of new traits. We have all the needed reagents in place to carry out this project,
including necessary bat and primate genomes as well as tissues from both insectivorous and frugivorous bats,
fasted and treated or untreated with fruit, and phenotypically relevant bat and primate cell lines for MPRA.
Importantly, we have all the needed expertise in our lab, routinely carrying out comparative and functional
genomic assays, MPRAs and mouse engineering. With our resources and proficiency, we are in the apt
position to advance understanding of the complex trait that is frugivory and ultimately genotype-phenotype
relationships.
Broader Impacts:
This research will improve genotype-phenotype predictions with re...

## Key facts

- **NIH application ID:** 10439977
- **Project number:** 1R01HG012396-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Nadav Ahituv
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $368,385
- **Award type:** 1
- **Project period:** 2022-01-14 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10439977

## Citation

> US National Institutes of Health, RePORTER application 10439977, EDGE CMT: Genomic characterization of mammalian adaptation to frugivory (1R01HG012396-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10439977. Licensed CC0.

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