The Molecular Heterogeneity of Natural Cordyceps sinensis with Multiple Ophiocordyceps sinensis Fungi Challenges the Anamorph-Teleomorph Connection Hypotheses

Natural Cordyceps sinensis is a traditional Chinese medicine with a long history of use as a folk medicine in China. However, whether Ophiocordyceps sinensis is a single fungus or a collective name for multiple fungi remains controversial, as does the anamorph-teleomorph connection of O. sinensis. Although Hirsutella sinensis has been widely considered the sole anamorph of O. sinensis, direct evidence supporting this hypothesis is lacking. This paper reviews the molecular heterogeneity findings of C. sinensis studies and the issues with the hypotheses of the anamorph-teleomorph connection of O. sinensis. Molecular analyses have revealed the coexistence of multiple fungi and multiple genotypes of O. sinensis in natural C. sinensis. Mutant sequences from at least 11 O. sinensis genotypes are registered in GenBank and represent individual fungi distinct from the genome sequence of H. sinensis, which is inconsistent with the “sole anamorph” and “ITS pseudogenes” hypotheses. Together, the multicellular C. sinensis ascospores with mono-/bi-/trinucleate structures in each ascospore and the detection of at least 2 O. sinensis genotypes in the culture of heterokaryotic single-ascospore isolates challenge the study conclusions based on microcycle conidiation of C. sinensis ascospores. During C. sinensis maturation, the fungi that grow differentially in the caterpillar body and stroma of C. sinensis undergo asynchronous, dynamic alterations, supporting the integrated microecosystem hypothesis for natural C. sinensis proposed by Prof. Zongqi Liang.