The genome of the wheat and cereal pathogen Fusarium graminearum was published in Science this week in an article entitled “The Fusarium graminearum Genome Reveals a Link Between Localized Polymorphism and Pathogen Specializationtion”. The project was a collaboration of many different Fusarium research groups. The genome sequencing was spearheaded by the Broad Institute at Harvard and MIT and is part of a larger project to sequence several different species of Fusarium. The group sequenced a second strain in order to identify polymorphisms.
Some of the key findings
- The presence of Repeat Induced point-mutation (RIP) has likely limited the amount of repetitive and duplicated sequences in the genome
- Most of the genes unique to F. graminearum (and thus not present in 4 other Fusarium spp genomes) are found in the telomeres
- Between the sequenced strains SNP density ranged from 0 to 17.5 polymorphisms per kb.
- Some of the genes expressed uniquely during plant infection (408 total) include known virulence factors and many plant cell-wall degrading enzymes.
- The genes showing some of the highest SNP diversity tended to be unique to Fusarium and often unique to F. graminearum
Aspergillus fumigatus can be dangerous, even to those with intact immune systems. A recent article in Discover magazine’s Vital Signs describes how dangerous the ubiquitous fungus can be.
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.
The Broad Institute has made available additional genomes of strains of Coccidioides immitis and C. posadasii. There are now genome sequences for 4 strains of C. immitis sequenced and 3 strains of C. posadasii including the C735 strain from the JCVI/TIGR. including the reference strain RS that is assembled into 7 supercontigs (there are probably 5 chromosomes) and annotated with ~10,000 genes. However we think at least ~1-2k of the annotated genes in strain RS are likely reptitive sequences and not real genes based on comparisons with the TIGR annotations of C. posadasii C735 strain and de novo repeat finding and analysis – John talked about this in his talk at Asilomar.
Thse available strain sequences are going to allow for some interesting analyses that have yet to be applied in fungi. This includes doing some whole genome scans for selection using more sensitive population genetic tests than the gross-level non-synonymous /synonymous ratio tests that we’ve been relegated to with the current comparisons and it is starting to feel a bit like when “all you have is a hammer…”. Now all we have to do is get the whole genome multi-strain alignment quirks worked out and probably have to do our own quick annotation since only the two reference strains are annotated.
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 exciting research paper “Control of alternative RNA splicing and gene expression by eukaryotic riboswitches” published in Nature details the mechanism of how riboswitches work in Neurospora crassa. While riboswitches have been found and studied in bacteria there has not been extensive work showing how they work in fungi. In bacteria the riboswitch acts as the direct interacting sensor that switches gene expression off through a structural change in the RNA and fit in nicely with the RNA world view.
Using N. crassa, the authors show that alternative splicing is directly regulated through the thiamine metabolism genes which contains previously identified riboswitches. As also highlighted in the accompanying commentary this is also an interesting examples of direct RNA regulation of alternative splicing rather than through peptides like SR proteins.
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
The genome sampling in the Eurotiomycota clade just keeps getting better. The new J. Crag Venter Institute (TIGR) deposited WGS Assemblies of the human pathogens Penicillium marneffei and Talaromyces stipitatus. P. marneffei is a thermally dimorphic fungus endemic to South-East Asia found in bamboo rats. It is studied by a number of labs and the genome will aid in many of the studies including the population structure through MLST studies.
Lots of papers in Mycologia (subscription required) this month of different groups analyzing the fine-scale relationships of many different fungal clades using the loads of sequences that were generated as part of the Fungal Tree of Life project.
Some highlights – there are just too many papers in the issue to cover them all. As usual with more detailed studies of clades with molecular sequences we find that morphologically defined groupings aren’t always truly monophyletic and some species even end up being reclassified. Not that molecular sequence approaches are infallable, but for many fungi the morphological characters are not always stable and can revert (See Hibbet 2004 for a nice treatment of this in mushrooms; subscription required).
- Meredith Blackwell and others describe the Deep Hypha research coordination network that helped coordinate all the Fungal Tree of Life-rs.
- John Taylor and Mary Berbee update their previous dating work with new divergence dates for the fungi using as much of the fossil evidence as we have.
- The early diverging Chytridiomycota, Glomeromycota, and Zygomycota are each described. Tim James and others present updated Chytridiomycota relationships so of which were only briefly introducted in the kingdom-wide analysis paper published last year.
- There is a nice overview paper of the major Agaricales clades (mushrooms for the non-initiated) from Brandon Matheny as well as as individual treatment of many of the sub-clades like the cantharelloid clade (mmm chanterelles…) .
- Relationships of the Puccinia clade are also presented – we blogged about the wheat pathogen P. graminis before.
- A new Saccharomycetales phylogeny is presented by Sung-Oui Suh and others.
- The validity of the Archiascomycete group is also tested (containing the fission yeast Schizosaccharomyces pombe and the mammalian pathogen Pneumocystis) and they confirm that it is basal to the two sister clades the euascomycete (containing Neurospora) and hemiascomycete (containing Saccharomyces) clades. However it doesn’t appear there are enough sampled species/genes to confirm monophyly of the group. There are/will be soon three genome sequences of Schizosaccharomyces plus one or two Pneumocystis genomes – it will be interesting to see how this story turns out if more species can be identified.
This was a monster effort by a lot of people who it is really nice to see it all have come together in what looks like some really nice papers.
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.