Elsevier

Hormones and Behavior

Volume 126, November 2020, 104850
Hormones and Behavior

Review article
Inside the supergene of the bird with four sexes

https://doi.org/10.1016/j.yhbeh.2020.104850Get rights and content

Abstract

The white-throated sparrow (Zonotrichia albicollis) offers unique opportunities to understand the adaptive value of supergenes, particularly their role in alternative phenotypes. In this species, alternative plumage morphs segregate with a nonrecombining segment of chromosome 2, which has been called a ‘supergene’. The species mates disassortatively with respect to the supergene; that is, each breeding pair consists of one individual with it and one without it. This species has therefore been called the “bird with four sexes”. The supergene segregates with a behavioral phenotype; birds with it are more aggressive and less parental than birds without it. Here, we review our efforts to identify the genes inside the supergene that are responsible for the behavioral polymorphism. The gene ESR1, which encodes estrogen receptor α, differs between the morphs and predicts both territorial and parental behavior. Variation in the regulatory regions of ESR1 causes an imbalance in expression of the two alleles, and the degree to which this imbalance favors the supergene allele predicts territorial singing. In heterozygotes, knockdown of ESR1 causes a phenotypic switch, from more aggressive to less aggressive. We recently showed that another gene important for social behavior, vasoactive intestinal peptide (VIP), is differentially expressed between the morphs and predicts territorial singing. We hypothesize that ESR1 and VIP contribute to behavior in a coordinated way and could represent co-adapted alleles. Because the supergene contains more than 1000 individual genes, this species provides rich possibilities for discovering alleles that work together to mediate life-history trade-offs and maximize the fitness of alternative complex phenotypes.

Section snippets

The sparrow with four sexes

Plate 8 of Audubon's Birds of America features two white-throated sparrows (Zonotrichia albicollis). One has black and white stripes on its crown and a clear white throat; the other has brown and tan stripes and a streaked throat. In his painting, Audubon labeled them male and female, respectively. Field guides also labeled them as such, or as adult and juvenile, until the early 1960s. Working with hundreds of specimens, Lowther (1961) discovered that Audubon and the field guides alike had been

The ZAL2m rearrangement is a special kind of supergene

When a group of alleles is inherited together and collectively controls a complex, adaptive phenotype, it is called a ‘supergene’ (reviewed by Schwander et al., 2014; Thompson & Jiggins, 2014). The co-inheritance, which is key to this concept, is caused by tight linkage disequilibrium. Recombination within supergenes is suppressed, often because of inversions. After an inversion occurs, the affected haplotype can no longer easily recombine with its counterpart, due to the disruption of synapsis

Connecting genotype to phenotype

The genetic variation that underlies phenotypic variation can occur in coding sequences or regulatory sequences, which may affect either protein structure or levels of gene expression, respectively. For most of the 20th century, researchers were interested primarily in the effects of mutations in coding regions. These mutations were an obvious place to begin investigation because coding regions govern the sequence of amino acids that build proteins. Non-synonymous mutations, or mutations that

Estrogen receptor α

Accumulating evidence that the morph differences in social behavior depend on reproductive hormones (Maney and Goodson, 2011; Maney et al., 2009) suggests that these behavioral differences may depend on differentiation of hormone signaling pathways. One of the genes within this pathway, and also inside the ZAL2m/ZAL2 rearrangement, is ESR1, the gene that encodes estrogen receptor α (ERα). The ERα protein binds estrogens, particularly E2, a major metabolite of testosterone that can be

Vasoactive intestinal peptide

We next turned our attention to a different gene inside the ZAL2m/ZAL2 rearrangement, VIP, which encodes vasoactive intestinal peptide. This 28-amino acid polypeptide, which is highly conserved among vertebrates, was named after its role in regulating gastrointestinal blood flow and vasodilation (reviewed by Klimaschewski, 1997; Lee et al., 1984). It has since been found to be widespread throughout the vertebrate brain and critical in the regulation of social behavior (Kingsbury, 2015;

Inversions and complex alternative phenotypes: back to Dobzhansky?

Social behaviors are complex and polygenic. Thus, we should expect that understanding their genetic basis will require careful consideration of multiple genes and how they are regulated. The ZAL2m supergene in white-throated sparrows has captured variant alleles of ESR1 and VIP that seem to confer high levels of expression in TnA and AH, respectively (Figs. 4C, 5A, B; Horton et al., 2014b, Horton et al., 2020). Existing evidence, from this species and other songbirds, suggests that the

Supergenes: diverse phenotypes, similar challenges

The white-throated sparrow is not the only species with a supergene linked to life-history strategies. In a shorebird called the ruff (Philomachus pugnax), an inversion polymorphism underlies a complex mating system with three different male morphs: territorial males with showy plumage, satellite males, which form temporary alliances with territorial males, and female-like faeders, which sneak copulations (Küpper et al., 2016; Lamichhaney et al., 2016). Whereas the territorial males are

Acknowledgments

We thank Nicole Baran, Katie Grogan, Harris Jeong, Clifton McKee, Christina Michael, Justin Michaud, Eric Ortlund, Sandra Shirk, Dan Sun, Jim Thomas, Emily Young, and Wendy Zinzow-Kramer for their contributions to this work.

Funding

This work was supported by NIH Grant 1R01MH082833 to D.L.M and S.V.Y., NSF Grant IOS-1627789 to D.L.M and S.V.Y., and NIH Grant 1F31MH114509 to J.R.M.

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