A genome scan of diversifying selection in Ophiocordyceps zombie-ant fungi suggests a role for enterotoxins in co-evolution and host specificity

Mol Ecol. 2018 Sep;27(18):3582-3598. doi: 10.1111/mec.14813. Epub 2018 Aug 29.


Identification of the genes underlying adaptation sheds light on the biological functions targeted by natural selection. Searches for footprints of positive selection, in the form of rapid amino acid substitutions, and the identification of species-specific genes have proved to be powerful approaches to identifying the genes involved in host specialization in plant-pathogenic fungi. We used an evolutionary comparative genomic approach to identify genes underlying host adaptation in the ant-infecting genus Ophiocordyceps, which manipulates ant behaviour. A comparison of the predicted genes in the genomes of species from three species complexes-O. unilateralis, O. australis and O. subramanianii-revealed an enrichment in pathogenesis-associated functions, including heat-labile enterotoxins, among species-specific genes. Furthermore, these genes were overrepresented among those displaying significant footprints of positive selection. Other categories of genes suspected to be important for virulence and pathogenicity in entomopathogenic fungi (e.g., chitinases, lipases, proteases, core secondary metabolism genes) were much less represented, although a few candidate genes were found to evolve under positive selection. An analysis including orthologs from other entomopathogenic fungi in a broader context showed that positive selection on enterotoxins was specific to the ant-infecting genus Ophiocordyceps. Together with previous studies reporting the overexpression of an enterotoxin during behavioural manipulation in diseased ants, our findings suggest that heat-labile enterotoxins are important effectors in host adaptation and co-evolution in the Ophiocordyceps entomopathogenic fungi.

Keywords: Ophiocordyceps; adaptation; enterotoxins; host specificity; positive selection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ants / microbiology*
  • Enterotoxins / genetics*
  • Genes, Fungal
  • Genomics
  • Host Specificity*
  • Hypocreales / classification
  • Hypocreales / genetics*
  • Phylogeny
  • Selection, Genetic*
  • Species Specificity
  • Virulence / genetics


  • Enterotoxins