Chromosome rearrangements shape the diversification of secondary metabolism in the cyclosporin producing fungus Tolypocladium inflatum

Rodrigo Olarte, Jon R Menke, Ying Zhang, Shawn Sullivan, Jason C. Slot, Yinyin Huang, Jon Badalamenti, Alisha C. Quandt, Joseph W. Spatafora, Kathryn E Bushley

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Background: Genes involved in production of secondary metabolites (SMs) in fungi are exceptionally diverse. Even strains of the same species may exhibit differences in metabolite production, a finding that has important implications for drug discovery. Unlike in other eukaryotes, genes producing SMs are often clustered and co-expressed in fungal genomes, but the genetic mechanisms involved in the creation and maintenance of these secondary metabolite biosynthetic gene clusters (SMBGCs) remains poorly understood. Results: In order to address the role of genome architecture and chromosome scale structural variation in generating diversity of SMBGCs, we generated chromosome scale assemblies of six geographically diverse isolates of the insect pathogenic fungus Tolypocladium inflatum, producer of the multi-billion dollar lifesaving immunosuppressant drug cyclosporin, and utilized a Hi-C chromosome conformation capture approach to address the role of genome architecture and structural variation in generating intraspecific diversity in SMBGCs. Our results demonstrate that the exchange of DNA between heterologous chromosomes plays an important role in generating novelty in SMBGCs in fungi. In particular, we demonstrate movement of a polyketide synthase (PKS) and several adjacent genes by translocation to a new chromosome and genomic context, potentially generating a novel PKS cluster. We also provide evidence for inter-chromosomal recombination between nonribosomal peptide synthetases located within subtelomeres and uncover a polymorphic cluster present in only two strains that is closely related to the cluster responsible for biosynthesis of the mycotoxin aflatoxin (AF), a highly carcinogenic compound that is a major public health concern worldwide. In contrast, the cyclosporin cluster, located internally on chromosomes, was conserved across strains, suggesting selective maintenance of this important virulence factor for infection of insects. Conclusions: This research places the evolution of SMBGCs within the context of whole genome evolution and suggests a role for recombination between chromosomes in generating novel SMBGCs in the medicinal fungus Tolypocladium inflatum.

Original languageEnglish (US)
Article number120
JournalBMC Genomics
Issue number1
StatePublished - Feb 7 2019

Bibliographical note

Funding Information:
This research was supported by an NSF postdoctoral fellowship to RO (DBI-1402140) and Startup Funding from the University of Minnesota to KEB. The funding agency had no role in in the design of the study, collection, analysis, and interpretation of data, or in writing the manuscript.

Publisher Copyright:
© 2019 The Author(s).


  • Chromosome rearrangement
  • Fungi
  • Genome evolution
  • Hi-C
  • Secondary metabolism
  • Structural variation


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