Differential Retention of Gene Functions in a Secondary Metabolite Cluster

Mol Biol Evol. 2017 Aug 1;34(8):2002-2015. doi: 10.1093/molbev/msx145.


In fungi, distribution of secondary metabolite (SM) gene clusters is often associated with host- or environment-specific benefits provided by SMs. In the plant pathogen Alternaria brassicicola (Dothideomycetes), the DEP cluster confers an ability to synthesize the SM depudecin, a histone deacetylase inhibitor that contributes weakly to virulence. The DEP cluster includes genes encoding enzymes, a transporter, and a transcription regulator. We investigated the distribution and evolution of the DEP cluster in 585 fungal genomes and found a wide but sporadic distribution among Dothideomycetes, Sordariomycetes, and Eurotiomycetes. We confirmed DEP gene expression and depudecin production in one fungus, Fusarium langsethiae. Phylogenetic analyses suggested 6-10 horizontal gene transfers (HGTs) of the cluster, including a transfer that led to the presence of closely related cluster homologs in Alternaria and Fusarium. The analyses also indicated that HGTs were frequently followed by loss/pseudogenization of one or more DEP genes. Independent cluster inactivation was inferred in at least four fungal classes. Analyses of transitions among functional, pseudogenized, and absent states of DEP genes among Fusarium species suggest enzyme-encoding genes are lost at higher rates than the transporter (DEP3) and regulatory (DEP6) genes. The phenotype of an experimentally-induced DEP3 mutant of Fusarium did not support the hypothesis that selective retention of DEP3 and DEP6 protects fungi from exogenous depudecin. Together, the results suggest that HGT and gene loss have contributed significantly to DEP cluster distribution, and that some DEP genes provide a greater fitness benefit possibly due to a differential tendency to form network connections.

Keywords: depudecin; gene cluster; horizontal gene transfer; phylogenetic analysis; pseudogenization; secondary metabolites.

Publication types

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

MeSH terms

  • Alkadienes / metabolism*
  • Ascomycota / genetics
  • Databases, Nucleic Acid
  • Epoxy Compounds / metabolism*
  • Evolution, Molecular
  • Fatty Alcohols / metabolism*
  • Fungal Proteins / genetics
  • Fusarium / genetics
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Fungal / genetics
  • Gene Transfer, Horizontal / genetics
  • Genome, Fungal / genetics*
  • Multigene Family / genetics*
  • Phylogeny
  • Secondary Metabolism / genetics
  • Virulence / genetics


  • Alkadienes
  • Epoxy Compounds
  • Fatty Alcohols
  • Fungal Proteins
  • depudecin