Genus-level studies of gene dynamics for the Aspergillus genus

Sebastian Theobald

Research output: Book/ReportPh.D. thesis

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Abstract

The fungal genus Aspergillus has a great impact on society. It includes species with industrial value A. niger and A. oryzae, medically relevant species Aspergillus fumigatus and A. terreus, and the model organisms A. nidulans. A. nidulans, chosen as model organism due to its sexual cycle and possibility to study genetics using spore color, provided insights into key regulators of cell cycle control, development and secondary metabolism. Results obtained from studies on A. nidulans were found to be applicable on other Aspergilli as well. Genome sequencing of A. nidulans, A. fumigatus and A. oryzae further revealed a large phylogenetic distance between species of the genus. Hence, conclusions derived from studies on model organisms might not apply to the genus as a whole but rather on smaller taxonomical groups. Taxonomy of Aspergilli is constantly under evaluation and the information added by new methods and technologies is aiding the definition of new taxonomic groups (Chen et al., 2016; Hubka et al., 2016). In the 300 Aspergillus genome project, we are extending the set of sequenced species to further investigate genome and gene diversity across the entire genus. This specific project deals with the diversity of secondary metabolite (SM) genes and conservation of regulators. To achieve a comparison of several species at once, we created methods which classify genes into families. This approach highlighted that regulators like mcrA, a master regulator of secondary metabolism, is conserved throughout Aspergilli and that galR, a regulator which was thought to be unique for A. nidulans is present in many other species. SM genes needed a slightly different type of clustering since they show high similarity between each other — making them difficult to separate. The full pathway for a secondary metabolite is encoded on a spatial collective of genes, a secondary metabolite gene cluster (SMGC). Thus, to find families of SMGC for production of similar SMs we compared whole gene clusters against each other. Our analysis highlights differences of SMGC families shared on several taxonomic levels. Characterizing regulators and SMGC over several species as families has the advantage that we are able to follow their distribution throughout the
genus. This has several benefits. Examination of conserved genes can give insights into the adaptations of a section of Aspergilli. Examining SMGC
families can give hints to uninvestigated SMGC producing promising drug leads. Overall, analyzing Aspergillus species with this comparative approach will reveal their gene dynamics and diversity and give insights into adaptations of sections throughout the genus.
Original languageEnglish
Place of PublicationKgs. Lyngby
PublisherTechnical University of Denmark
Number of pages166
Publication statusPublished - 2018

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