title: The evolution of cardenolide-resistant forms of Na⁺,K⁺ -ATPase in Danainae butterflies.
abstract: Cardenolides are a class of plant secondary compounds that inhibit the proper functioning of the Na(+) , K(+) -ATPase enzyme in susceptible animals. Nonetheless, many insect species are able to sequester cardenolides for their own defence. These include butterflies in the subfamily Danainae (Family: Nymphalidae) such as the monarch (Danaus plexippus). Previous studies demonstrated that monarchs harbour an asparagine (N) to histidine (H) substitution (N122H) in the α subunit of Na(+) , K(+) -ATPase (ATPα) that reduces this enzyme's sensitivity to cardenolides. More recently, it has been suggested that at ATPα position 111, monarchs may also harbour a leucine (L)/glutamine (Q) polymorphism. This later amino acid could also contribute to cardenolide insensitivity. However, here we find that incorrect annotation of the initially reported DNA sequence for ATPα has led to several erroneous conclusions. Using a population genetic and phylogenetic analysis of monarchs and their close relatives, we show that an ancient Q111L substitution occurred prior to the radiation of all Danainae, followed by a second substitution at the same site to valine (V), which arose before the diversification of the Danaus genus. In contrast, N122H appears to be a recent substitution specific to monarchs. Surprisingly, examination of a broader insect phylogeny reveals that the same progression of amino acid substitutions (Q111L → L111V + N122H) has also occurred in Chyrsochus beetles (Family: Chrysomelidae, Subfamily: Eumolpinae) that feed on cardenolide-containing host plants. The parallel pattern of amino acid substitution in these two distantly related lineages is consistent with an adaptive role for these substitutions in reducing cardenolide sensitivity and suggests that their temporal order may be limited by epistatic interactions.
authors: Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544, USA. maardema@princeton.edu
authors: Matthew L
authors: ML
authors: Aardema
authors: Ying
authors: Y
authors: Zhen
authors: Peter
authors: P
authors: Andolfatto
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D005075:Biological Evolution; D002080:Butterflies / Q000201:enzymology / Q000235:genetics*; D002298:Cardenolides / Q000378:metabolism*; D005828:Genetics, Population; D049750:Genome, Insect; D010802:Phylogeny; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics* / Q000378:metabolism
chemical_list: D002298:Cardenolides; D000254:Sodium-Potassium-Exchanging ATPase