The evolution of cardenolide-resistant forms of Na +,K +-ATPase in Danainae butterflies

Matthew Aardema, Ying Zhen, Peter Andolfatto

Research output: Contribution to journalArticleResearchpeer-review

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 â 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.

Original languageEnglish
Pages (from-to)340-349
Number of pages10
JournalMolecular Ecology
Volume21
Issue number2
DOIs
StatePublished - 1 Jan 2012

Fingerprint

Danainae
Cardenolides
cardenolides
Butterflies
sodium-potassium-exchanging ATPase
butterfly
butterflies
substitution
amino acid substitution
Amino Acid Substitution
amino acid
adenosinetriphosphatase
Insects
Adenosine Triphosphatases
Danaus
harbor
Danaus plexippus
insects
insect
enzyme

Keywords

  • cardiac glycosides
  • Danainae
  • Danaus plexippus
  • milkweed
  • molecular adaptation
  • monarch butterfly
  • parallel evolution

Cite this

Aardema, Matthew ; Zhen, Ying ; Andolfatto, Peter. / The evolution of cardenolide-resistant forms of Na +,K +-ATPase in Danainae butterflies. In: Molecular Ecology. 2012 ; Vol. 21, No. 2. pp. 340-349.
@article{9d6898c731d5487db392ab63119e03bd,
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 {\^a} 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.",
keywords = "cardiac glycosides, Danainae, Danaus plexippus, milkweed, molecular adaptation, monarch butterfly, parallel evolution",
author = "Matthew Aardema and Ying Zhen and Peter Andolfatto",
year = "2012",
month = "1",
day = "1",
doi = "10.1111/j.1365-294X.2011.05379.x",
language = "English",
volume = "21",
pages = "340--349",
journal = "Molecular Ecology",
issn = "0962-1083",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "2",

}

The evolution of cardenolide-resistant forms of Na +,K +-ATPase in Danainae butterflies. / Aardema, Matthew; Zhen, Ying; Andolfatto, Peter.

In: Molecular Ecology, Vol. 21, No. 2, 01.01.2012, p. 340-349.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - The evolution of cardenolide-resistant forms of Na +,K +-ATPase in Danainae butterflies

AU - Aardema, Matthew

AU - Zhen, Ying

AU - Andolfatto, Peter

PY - 2012/1/1

Y1 - 2012/1/1

N2 - 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 â 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.

AB - 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 â 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.

KW - cardiac glycosides

KW - Danainae

KW - Danaus plexippus

KW - milkweed

KW - molecular adaptation

KW - monarch butterfly

KW - parallel evolution

UR - http://www.scopus.com/inward/record.url?scp=84855421807&partnerID=8YFLogxK

U2 - 10.1111/j.1365-294X.2011.05379.x

DO - 10.1111/j.1365-294X.2011.05379.x

M3 - Article

VL - 21

SP - 340

EP - 349

JO - Molecular Ecology

JF - Molecular Ecology

SN - 0962-1083

IS - 2

ER -