Summary: Blocking expression of the ER-alpha gene in white-throated sparrows reduces their aggression.
Source: Emory Health Sciences
New research reveals how variation in a single gene within a supergene alters behavior in a wild songbird, determining whether the white-throated sparrow exhibits higher or lower levels of aggression. The study, led by neuroscientists at Emory University, appears in the Proceedings of the National Academy of Sciences (PNAS).
The team focused on estrogen receptor alpha (ER-alpha, encoded by ESR1), a gene embedded within a larger cluster of more than 1,000 genes known as a supergene. Supergenes form when a section of a chromosome is flipped and locked by inversions, causing the genes inside to be inherited as a unit. By isolating ER-alpha, the researchers were able to trace how changes in a single gene contribute to distinct behavioral phenotypes in a vertebrate.
“Evolution has introduced small sequence changes to this gene in the white-throated sparrow, and we demonstrated that those changes affect both how the gene is expressed in the brain and how the bird behaves,” says Jennifer Merritt, an Emory doctoral student and first author on the paper.
Merritt conducted the work in the laboratory of Donna Maney, senior author and professor of psychology at Emory. White-throated sparrows are widespread across much of North America and display two clear morphs: a white-striped form with bold black, white, and yellow markings, and a tan-striped form with more subdued tan and gray plumage. These morphs differ not only in appearance but also in reproductive strategy and social behavior.
All white-striped individuals carry at least one copy of the rearranged chromosome that contains the supergene; these birds are generally more aggressive and less parental than tan-striped birds that lack the rearrangement. Because supergenes keep many genes linked together, it is difficult to determine which specific gene—or genes—drive behavioral differences. The Maney lab leveraged their extensive knowledge of the species’ natural history and prior molecular findings to pinpoint ER-alpha as a candidate.
Earlier work from the Maney group showed that white-striped sparrows express ER-alpha at higher levels than tan-striped birds, and that higher expression correlates with increased aggression. In the current study the researchers connected genetic variation in ER-alpha to expression in the brain and then to measurable behavior in both wild and captive birds.
In field observations, the researchers measured aggressive territorial behavior by recording song rate and the frequency of physical charges at perceived intruders. Birds favoring the supergene version of ER-alpha sang more frequently and defended their territories more vigorously than birds expressing the standard allele.
To test causality, the team carried out experiments in the lab. They used a targeted intervention to reduce expression of ER-alpha in white-striped birds and then measured changes in aggression. When ER-alpha expression was blocked, the formerly more aggressive white-striped sparrows showed a marked reduction in territorial aggression and behaved more like tan-striped birds.
“This is, to our knowledge, the first experimental demonstration that variation in a single gene within a supergene can drive changes in a social behavior in a wild vertebrate,” Merritt explains. She uses a river analogy to clarify the challenge: many linked genes are like tributaries feeding a river (the behavior), and their work identifies which tributary—ER-alpha—contributes significantly to flow changes.
The Maney laboratory continues to investigate other neuroendocrine genes captured by the chromosomal rearrangement, aiming to map how multiple regulatory elements and gene interactions shape social behavior. Their approach combines field ecology, neurogenetics, and behavioral assays to move from sequence variation to function and then to observed behavior.
Co-authors include Eric Ortlund, a biochemist and ER-alpha specialist at the Emory School of Medicine; former Maney lab postdoctoral fellows Kathleen Grogan and Wendy Zinzow-Kramer; and collaborators Dan Sun and Soojin Yi from Georgia Tech.
Funding: Research was supported by grants from the National Institutes of Health and the National Science Foundation.
About this genetics research article
Source:
Emory Health Sciences
Contacts:
Carol Clark – Emory Health Sciences
Image Source:
Image credited to Jennifer Merritt.
Original Research: Closed access. “A supergene-linked estrogen receptor drives alternative phenotypes in a polymorphic songbird” by Jennifer R. Merritt, Kathleen E. Grogan, Wendy M. Zinzow-Kramer, Dan Sun, Eric A. Ortlund, Soojin V. Yi, and Donna L. Maney. Published in PNAS.
Abstract
A supergene-linked estrogen receptor drives alternative phenotypes in a polymorphic songbird
Behavioral evolution depends on genetic change, yet identifying the precise sequences responsible for behavioral differences in vertebrates remains uncommon. This study provides experimental evidence that differentiation of a single gene, ESR1 (encoding estrogen receptor α, ERα), has contributed to divergent behavioral phenotypes in the white-throated sparrow. A chromosomal inversion has generated a supergene that segregates with an aggressive morph. ERα, captured by the supergene, shows sequence and regulatory changes that distinguish the supergene allele from the standard allele. Knockdown of ERα in the more aggressive birds produced a shift toward the less aggressive phenotype, and allelic imbalance in wild populations predicts aggression in the field. The authors also identify genetic and epigenetic cis-regulatory features that explain the allelic imbalance, providing a clear example of how genotypic divergence can lead to behavioral divergence in a vertebrate.