Evolution of aflatoxin gene cluster

Jason Stajich — Sat, 29 Sep 2007 20:17:06 +0000

Ignazio Carbone and colleagues published a recent analysis of the evolution of the aflatoxin gene cluster in five Aspergillus fungi entitled “Gene duplication, modularity and adaptation in the evolution of the aflatoxin gene cluster” in BMC Evolutionary Biology. The authors were able to identify seven modules pairs of genes whose history of duplication were highly correlated. Several genomes of Aspergillus have been sequenced along with more Eurotioales fungi.In the Carbone et al manuscript, Figure 2 shows the pattern of duplication among members o the cluster with panel A showing the relative number of duplicates of each gene and the colors representing the species containing the duplicates. I would be interested in an even more systematic study of duplication patterns in the Eurotiales and Aspergilli as several classes of genes like sugar transporters and enzymes related to saprobic growth and plant matter degradation are also expanded. I expect that this pattern of duplication is unexpectedly high, but wonder how broadly it can be seen across the clade.The authors use panel B to explore the correlation of duplications so for example, in purple, the aflT/aflQ gene pairs are closest in the dendrogram indicating their duplication pattern is highly correlated even though they are not physically adjacent. It would be helpful to have a better description of substrates that the individual enzymes can utilize if there is some relationship between the compounds for genes with correlated duplication history. Certainly the order and specificity/generality of enzymes needed in a pathway correlates with patterns of molecular evolution as seen in Anthocyanin biosynthesis for example and recent unpublished work presented at SMBE2007 from Dave Des Marais showed that patterns of selection on duplicated genes is indicative of subfunctionalization.Figure 3 shown below, shows the gene order reconstruction in several of the Aspergillus genomes studied in attempt to identify the overall clustering of these genes across the lineages. The authors conclude from this reconstruction that reorganization to bring these genes together happened more recently stating:

We hypothesize that gene modules that are contiguous in one species and noncontiguous in others are the result of rearrangements in an ancestral species.

This sort of rearrangement of a cluster to bring together genes has been seen such as the DAL cluster in Saccharomyces.I don’t know how much further research has been done to identify other putative clusters through comparative analyses. Certainly this was looked at in recent comparative genome paper but I don’t recall any major identification of new biosynthesis clusters based on unexpected synteny or clustering of PKS or NRPS genes.

Exploring a global regulator of gene expression in Aspergillus

Jason Stajich — Mon, 25 Jun 2007 10:41:35 +0000

When first discovered, the gene LaeA was thought to be a master switch for silencing of several NRPS secondary metabolite gene clusters in Aspergillus. NRPS and PKS are important genes in filamentous fungi as they produce many compounds that likely help fungi compete in the ecological niche mycotoxins (e.g. aflatoxin, gliotoxin), plant hormone (e.g. Gibberellin), and a potential wealth of additional undiscovered activities.

A recent paper from Nancy Keller’s lab entitled Transcriptional Regulation of Chemical Diversity in Aspergillus fumigatus by LaeA has followed up previous studies with whole genome expression profiling of a LaeA knockout strain to explore the breadth of the genome that is regulated by this transcriptional regulator. The exact mechanism of LaeA silencing is not fully understood although it is thought to act via chromatin remodeling. There was some debate as to whether or not the pathway regulated production of a specific toxin that regulates virulence or if it was master regulator that controlled several different metabolite production pathways. Î”LaeA was hypovirulent but yet individual knockout of a known toxin like the gliotoxin NRPS did not show attenuated virulence. So LaeA much be regulating additional genes besides gliotoxin.

The Perrin et al study sought to explore this relationship through whole genome expression profiling. They found that LaeA influences the expression (positively or negatively) of at least 9.5% of the genome and that it positively controls the expression of 20-40% of the major secondary metabolite pathways including not only NRPSs, but Polyketide synthases (PKS), and P450 monooxygenases genes. This helps resolve some of the conflicting results from different knockout experiments.

It also provides an interesting window into how these genes and gene clusters may have evolved. There aren’t a lot of good examples of global regulation by chromatin silencing in fungi. The MAT HML and HMR cassette silencing in Saccharomyces is one example and telomeric and centromeric silencing are another other. Future work here is will help dissect both the mechanism of silencing and the potential role it has in regulation of secondary metabolite genes and virulence factors in filamentous pathogens.

The Hyphal Tip » gene cluster

Evolution of aflatoxin gene cluster

Exploring a global regulator of gene expression in Aspergillus