PT  - JOURNAL ARTICLE
AU  - Abigail L. Lind
AU  - Jennifer H. Wisecaver
AU  - Catarina Lameiras
AU  - Fernando Rodrigues
AU  - Gustavo H. Goldman
AU  - Antonis Rokas
TI  - Drivers of genetic diversity in secondary metabolic gene clusters in a fungal population
AID  - 10.1101/149856
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 149856
4099  - http://biorxiv.org/content/early/2017/06/13/149856.short
4100  - http://biorxiv.org/content/early/2017/06/13/149856.full
AB  - Filamentous fungi produce a diverse array of secondary metabolites (SMs) critical for defense, virulence, and communication. The metabolic pathways that produce SMs are found in contiguous gene clusters in fungal genomes, an atypical arrangement for metabolic pathways in other eukaryotes. Comparative studies of filamentous fungal species have shown that SM gene clusters are often either highly divergent or uniquely present in one or a handful of species, hampering efforts to determine the genetic basis and evolutionary drivers of SM gene cluster divergence. Here we examined SM variation in 66 cosmopolitan strains of a single species, the opportunistic human pathogen Aspergillus fumigatus. Investigation of genome-wide population-level variation showed that A. fumigatus strains contained five general types of variation in SM gene clusters: non-functional gene polymorphisms, gene gain and loss polymorphisms, whole cluster gain and loss polymorphisms, allelic polymorphisms where different alleles corresponded to distinct, non-homologous clusters, and location polymorphisms in which a cluster was found to differ in its genomic location across strains. These polymorphisms affect the function of representative A. fumigatus SM gene clusters, such as those involved in the production of gliotoxin, fumigaclavine, and helvolic acid, as well as the function of clusters with undefined products. In addition to enabling the identification of polymorphisms whose detection requires extensive genome-wide synteny conservation (e.g., mobile gene clusters and non-homologous cluster alleles), our population genomics approach also implicated multiple underlying genetic drivers, including point mutations, recombination, genomic deletion and insertion events, as well as horizontal gene transfer from distant fungi. Finally, most of the population variants that we uncover have been previously hypothesized to contribute to SM gene cluster diversity across entire fungal classes and phyla. We suggest that the drivers of genetic diversity operating within a fungal population shown here are sufficient to explain SM cluster macroevolutionary patterns.