Data from: Concerted evolution reveals co-adapted amino acid substitutions in Na+K+ ATPase of frogs that prey on toxic toads

Gene duplication is an important source of evolutionary innovation, but
the functional distinction between duplicates can be opposed by ongoing
gene conversion between them. Here we document a tandem duplication of
Na+,K+-ATPase subunit α1 (ATP1A1) sharedby frogs in the genus
Leptodactylus,a group of species that feeds on toxic toads. One ATP1A1
paralog evolved resistance to toad toxins while the other paralog retained
ancestral susceptibility. Frequent non-allelic gene conversion homogenized
most of the paralog sequences,yet the two Leptodactylusparalogs are
distinguished by 12 amino acid substitutions that were maintained by
strong selection that counteracted gene conversion. Protein-engineering
experiments show that two substitutions substantially increase toxin
resistance, whereas the 10 additional substitutions mitigate deleterious
pleiotropic effects on enzyme function. Our results highlight how
neofunctionalized gene duplicates can help pinpoint functional
substitutions and their interactions with the genetic backgrounds on which
they arise.