A supergene-linked estrogen receptor drives alternative phenotypes in a polymorphic songbird

Proc Natl Acad Sci U S A. 2020 Sep 1;117(35):21673-21680. doi: 10.1073/pnas.2011347117. Epub 2020 Aug 17.


Behavioral evolution relies on genetic changes, yet few behaviors can be traced to specific genetic sequences in vertebrates. Here we provide experimental evidence showing that differentiation of a single gene has contributed to the evolution of divergent behavioral phenotypes in the white-throated sparrow, a common backyard songbird. In this species, a series of chromosomal inversions has formed a supergene that segregates with an aggressive phenotype. The supergene has captured ESR1, the gene that encodes estrogen receptor α (ERα); as a result, this gene is accumulating changes that now distinguish the supergene allele from the standard allele. Our results show that in birds of the more aggressive phenotype, ERα knockdown caused a phenotypic change to that of the less aggressive phenotype. We next showed that in a free-living population, aggression is predicted by allelic imbalance favoring the supergene allele. Finally, we identified cis-regulatory features, both genetic and epigenetic, that explain the allelic imbalance. This work provides a rare illustration of how genotypic divergence has led to behavioral phenotypic divergence in a vertebrate.

Keywords: chromosomal inversion; social behavior; songbird.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aggression / physiology*
  • Animals
  • Behavior, Animal
  • Chromosome Inversion / genetics
  • Estrogen Receptor alpha / genetics*
  • Estrogens / genetics
  • Estrogens / metabolism
  • Female
  • Genotype
  • Male
  • Phenotype
  • Receptors, Estrogen / genetics
  • Social Behavior
  • Sparrows / genetics*


  • Estrogen Receptor alpha
  • Estrogens
  • Receptors, Estrogen