Genomic analyses reveal low mitochondrial and high nuclear diversity in the cyclosporin-producing fungus Tolypocladium inflatum.

Mitochondrial DNA is generally regarded to evolve faster than nuclear DNA in animals, whereas if this is also true in fungi remains unclear. Herein, we annotate the first complete mitochondrial genome (mitogenome) of the cyclosporin-producing fungus Tolypocladium inflatum and report the genome-wide sequence variations among five isolates originating from distantly separated localities. We found that T. inflatum has among the most compact of fungal mitogenomes; its 25 kb DNA molecule encodes all standard fungal mitochondrial genes and harbors only one intron. Transcriptional analyses validated the expression of most conserved genes. We found several uncommon repetitive elements and evidence of gene transfer from the mitochondrion to the nucleus. Phylogenetic analyses confirmed the placement of T. inflatum in the fungal order Hypocreales although there was uncertainty on its family-level affiliation. Comparative genomic analyses among the five isolates identified an overall lower level of intraspecific variation in mitogenomes than in nuclear genomes; however, both the nuclear and mitochondrial genomes revealed similar isolate relationships, not correlating with geographic sources of these isolates. Our study shed new insights into the evolution of the medicinally important ascomycete T. inflatum.