# A Unique Natural Model for Studying the Mechanisms Underlying Social Behavior

> **NIH NIH R01** · EMORY UNIVERSITY · 2020 · $263,782

## Abstract

SUMMARY
The genetic basis of social behavior is complex and involves many genes spread throughout the genome. As a
result, it has been difficult to link specific genes to social behavior in humans. Increasing accessibility to
genomic resources has now made it feasible to draw such connections in novel animal models. Well-chosen
models make possible an experimental, mechanistic strategy that begins at the level of gene variation and
works up through layers of biological organization, connecting each level to the one below, to explain the effect
of genetic variation on behavioral phenotype. The proposed research will leverage a large body of previous
work, conducted by the PI and collaborators, in a natural animal model uniquely suited for connecting genes
and social behavior. In the white-throated sparrow (Zonotrichia albicollis), a common North American songbird,
an inversion on chromosome 2 (ZAL2m) has significantly altered social strategies. Limited gene flow between
the ZAL2 and ZAL2m haplotypes has driven genetic differentiation of the rearranged region. As a direct result,
ZAL2m individuals of both sexes employ a life history strategy different from that of their ZAL2 counterparts –
they are more aggressive and less parental. The long-term goal is to use this inversion as a target to show how
a small genetic change can have large downstream effects on complex behavioral phenotypes. The PI and
collaborators have already identified a limited number of genes located inside the inversion that meet the
following criteria: (1) expression differs between birds with and without the inversion, (2) the genes show high
allele-specific expression in heterozygotes, and (3) expression is tightly correlated with vocal aggression.
These genes include a neuropeptide previously implicated in aggression, a serotonin receptor, and a
glutamate receptor. The objective of the proposed renewal application is to systematically evaluate the causal
effects of variation in these genes on aggressive phenotypes, working up through multiple levels of biological
organization from genotype to phenotype. First, the team will precisely identify the genetic variation responsible
for differential expression of these genes. Second, they will use bottom-up and targeted proteomics to show
the impact of genetic differentiation on the expression of protein isoforms in the brain. Finally, they will
manipulate production of the relevant proteins to test their roles in aggressive behavioral phenotypes. A major
strength of the research strategy is that the team will combine discovery-based, genome-wide approaches with
hypothesis-driven, targeted approaches, using the former to inform the latter. The project is innovative because
it takes advantage of a unique, powerful model organism that can be studied in its natural habitat. The
significance of this work is that it will move beyond genotype-phenotype associations to test for causal
connections between gene variants and social behavior...

## Key facts

- **NIH application ID:** 9858416
- **Project number:** 5R01MH082833-08
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** DONNA L MANEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $263,782
- **Award type:** 5
- **Project period:** 2010-04-15 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9858416

## Citation

> US National Institutes of Health, RePORTER application 9858416, A Unique Natural Model for Studying the Mechanisms Underlying Social Behavior (5R01MH082833-08). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9858416. Licensed CC0.

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