Review articleInside the supergene of the bird with four sexes
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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