Several more fungi are on the docket for sequencing at JGI through their community sequencing program. This includes
This complements an ever growing list of fungal genome sequences which is probably topping 80+ now not including the several dozen strains of Saccharomyces that are being sequenced at Sanger Centre and a separately funded NIH project to be sequenced at WashU.
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. Continue reading Exploring a global regulator of gene expression in Aspergillus
A nice evolutionary analysis of peroxin genes entitled PEX Genes in Fungal Genomes: Common, Rare, or Redundant in the journal “Traffic” from Kiel et al out of the University of Groningen in The Netherlands. Within a species, the genes in the PEX family are not necessarily phylogenetically related to each other, but instead are all named as to how they were discovered in mutant screens, most of which were done in S. cerevisiae.
Peroxisomes are interesting because they are necessary for some biochemical reactions (fatty acid metabolism). In filamentous fungi there are additionally specialized peroxisomes called Woronin bodies that plug the septal pore that separates individuals cells in a hyphae. These are specific to filamentous fungi so it is interesting to contrast the numbers and types of genes in the PEX family that are present as determined from the genome sequences. To relate this to human biology, the authors suggest that understanding the complex phenotypes of human peroxisome biogenesis disorders (PBD) will be helped through the study of the disruptions of PEX genes in various filamentous fungi. Interestingly, they find that nearly all PEX genes are present in all fungi, yeast and filamentous alike, although there may be additional genes unidentified.
Woronin bodies in A. nidulans from Momany et al, Mycologia 2002
Continue reading Evolution of PEX genes
As announced at the Fungal Genetics meeting, the FGI at the Broad Institute is focusing on clusters of genomes rather than single ones. Some of genome projects are already grouped.
- Coccidioides has 3 strains already plus the outgroup Uncinocarpus and conceivable one could include Histoplasma in there. This resources will grow to 14 strains (which comprise two species) of Coccidioides contributed by FGI and one from TIGR.
- Aspergillus currently has 8 species sequenced with several in pipeline at Broad and TIGR.
- Fusarium group has 3 species including recently released F. oxysporium.
- The Candida clade also have several different already sequenced genomes and of course there is the already well studied (and well utilized genome resources I’ll add) for the Saccharomyces clade.
- There are 4 genomes (well 5 but JEC21 and B-3501 are nearly identical) of Cryptococcus.
All in all a very exciting time for comparative genomics and I’m particularly intrigued to see how people will begin to use the resources.
This work to consolidate the clusters of genomes will, I hope, be very powerful. However, I still feel we are not doing a good job translating and centralizing information from different related species into a more centralized resource. Lots of money is spent on sequencing but I don’t know that we have realized the dream of having the comparative techniques illuminate the new genomes to the point that we are learning huge new things.
It seems to me, initially there is the lure of gathering low-hanging fruit from a genome analysis (which drives the first genome(s) paper), but not always the financial support of the longer term needs of the community to feed the experimental and functional work back into the genome annotation and interpretation.Â The cycle works really well for Saccharomyces cerevisiae because the curators who work with the community to insure information is deposited and that literature is gleaned to link genomic and functional information. But this is expensive in terms of funding many curators for many different projects.
It seems as we add more genomes there isn’t a very centralized effort for this type of curatorial information and so we lack the gems of high-quality annotation that is only seen in a few “model” systems.Â At some point a better meta-database that builds bridges between resource and literature rich “model system” communities may help, but maybe something new will have to be created? I like thinking about this as a user-driven content via a wiki which also dynamic (and versioned!) content from automated intelligent systems to map the straight-forward things.Â Tools like SCI-PHY already exist that can do this and generate robust orthology groups (or Books as the PhyloFact database organizes them) for futher analysis. The SGD wiki for yeast is a start at this, but is mostly an import of SGD data into a mediawiki framework – I wonder how this can be built upon in a more explictly comparative environment.
In a recent Microbiology Mini-Review, Meriel Jones catalogs both the potential benefits and problems that arise from fungal genome sequencing. Using the nine genomes (being) sequenced from the Aspergillus clade, Jones addresses several issues tied to a singular theme: if we are to unlock the potential that fungal genome sequencing holds, both academically and entrepreneurially, then a more robust infrastructure that enables comparative and functional annotation of genomes must be established.
Fortunately, like any good awareness advocate, Jones points us in the direction of e-Fungi, a UK based virtual project aimed at setting up such an infrastructure. Anyone can navigate this database to either compare the stored genomic information or evaluate any fungus of interest in the light of the e-Fungi genomic data. The data appears to be precomputed, similar to IMG from JGI, so there are inherent limitations on the data that one can obtain. However, tools such as these put important data in the hands of expert mycologists that can turn the information into something biologically meaningful.
As Jones points out, this is just the beginning. If fungal genomes are to live up to their promise, they must engage more than just experts at reading genomes.
The JGI has previously released A. niger strain ATCC 1015 sequence in November 2005. ATCC 1015 is used in industrial production of citric acid as it is one of the best producers of citric acid. In Nature Biotechnology a Dutch team has published the sequence of another strain, CBS 513.88 which is an early ancestor of ATCC 1015 used in industrial enzyme production.