Predictability in the evolution of Orthopteran cardenolide insensitivity

Philos Trans R Soc Lond B Biol Sci. 2019 Jul 22;374(1777):20180246. doi: 10.1098/rstb.2018.0246. Epub 2019 Jun 3.


The repeated evolutionary specialization of distantly related insects to cardenolide-containing host plants provides a stunning example of parallel adaptation. Hundreds of herbivorous insect species have independently evolved insensitivity to cardenolides, which are potent inhibitors of the alpha-subunit of Na+,K+-ATPase (ATPα). Previous studies investigating ATPα-mediated cardenolide insensitivity in five insect orders have revealed remarkably high levels of parallelism in the evolution of this trait, including the frequent occurrence of parallel amino acid substitutions at two sites and recurrent episodes of duplication followed by neo-functionalization. Here we add data for a sixth insect order, Orthoptera, which includes an ancient group of highly aposematic cardenolide-sequestering grasshoppers in the family Pyrgomorphidae. We find that Orthopterans exhibit largely predictable patterns of evolution of insensitivity established by sampling other insect orders. Taken together the data lend further support to the proposal that negative pleiotropic constraints are a key determinant in the evolution of cardenolide insensitivity in insects. Furthermore, analysis of our expanded taxonomic survey implicates positive selection acting on site 111 of cardenolide-sequestering species with a single-copy of ATPα, and sites 115, 118 and 122 in lineages with neo-functionalized duplicate copies, all of which are sites of frequent parallel amino acid substitution. This article is part of the theme issue 'Convergent evolution in the genomics era: new insights and directions'.

Keywords: K+-ATPase; Na+; Orthoptera; cardenolide; parallel evolution; pleiotropy; toxin insensitivity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biological Evolution
  • Cardenolides / pharmacology*
  • Herbivory / classification
  • Herbivory / drug effects*
  • Herbivory / genetics*
  • Insect Proteins / antagonists & inhibitors
  • Insect Proteins / genetics
  • Insect Proteins / metabolism
  • Insecta / chemistry
  • Insecta / classification
  • Insecta / genetics
  • Insecticide Resistance*
  • Insecticides / pharmacology*
  • Orthoptera / chemistry
  • Orthoptera / classification
  • Orthoptera / drug effects*
  • Orthoptera / genetics*
  • Phylogeny
  • Sequence Alignment
  • Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors
  • Sodium-Potassium-Exchanging ATPase / genetics
  • Sodium-Potassium-Exchanging ATPase / metabolism


  • Cardenolides
  • Insect Proteins
  • Insecticides
  • Sodium-Potassium-Exchanging ATPase

Associated data

  • figshare/10.6084/m9.figshare.c.4472423