Supergene evolution via gain of autoregulation

Development requires the coordinated action of many genes across space and
time, yet numerous species are able to develop multiple discrete,
alternate phenotypes. Such polymorphisms are often controlled by
supergenes, sets of tightly-linked loci that function together to control
development of a polymorphic phenotype. Although theories of supergene
evolution are well established, the functional genetic differences between
supergene alleles have been difficult to identify. The doublesex supergene
controls mimicry polymorphism in several Papilio swallowtail butterflies,
where divergent dsx alleles switch between discrete mimetic or non-mimetic
female wing patterns. Here we show that the Papilio alphenor supergene
evolved via recruitment of five new cis-regulatory elements (CREs) that
control allele-specific dsx expression. Most dsx CREs, including three of
the five new CREs, are bound by the DSX transcription factor itself.
Additionally, DSX differentially binds a small number of unlinked CREs
between mimetic and non-mimetic wings, suggesting that the supergene
directly regulates expression of unlinked modifier genes that execute the
mimetic development program. We thus identify the functional genetic
elements of a supergene; propose that autoregulation provides a simple
route to supergene origination and the evolution of dominance; and
establish a molecular mechanism for epistasis between supergenes and their
modifiers.