Tag Archives: systematics

A word about databases

Logo for fungal GenomesReport concludes that a fungal genome database is of “the highest priority”.

This is the title as listed in PubMed for this article from Future Medicine about the AAM report on charting future needs and avenues of research on the fungal kingdom.

The need for a comprehensive database for information about fungi, starting at least with systematic collections of genomic and transcript data, is highlighted as a major need.  Really and sort of new database effort should strive to be more comprehensive and include genetic and population data (alleles, strains) and information like protein-protein, protein-nucleic acid interactions (as Pedro mentioned). But on top of that it, it needs to be comparative so that information from systems that serve as great models can be transferred to other fungal systems that are being studied for their role as pathogens or interacting in the environmental.

Affordable next-gen sequencing will allow us to obtain genome and transcript sequence for basically all species or strains of interest.  Researchers with no bioinformatics support in their lab will likely be able to outsource this to a company or campus core facility.  But how can they easily map in the collective information about genes, proteins, and pathways onto this new data?  And have it be a dynamic system that can update as new information is published and curated in other systems.

I think this has to be the future beyond setting up a SGD, CGD, etc for every system.  The individual databases are useful for a large enough community where there are curators (and funding), but we will have to move to a more modular system in the future (aspects of which are in GMOD) that can have both an individual focus on a specific species/clade and a more comprehensive view of the that is comparable across the kingdom.  There are 100+ fungal genomes, but the community size for some of them are in the dozens of labs or less. How can they take advantage of the new resources without an existing infrastructure of curators?  Their systems serve an important need in a research aim, but how can discoveries there make its way back into the datastream of othe systems?

I see it as there are several ways one would interact with a system that provided single-genome tools as well as a framework for comparative information.  At a gene level, one might be looking for all information about a specific gene, based on sequence similarity searches, or starting with a cloned gene in one species. Something akin to Phylofacts or precomputed Orthogroups for defining a Gene but with more linking information about function by linking in information from all sources.  So a comparative resource, but also tapping into curated andliterature mined data.

At a genome level, one might want to do whole genome comparisons of gene content from evolutionarily defined families genes (gene family size change) or at a functional level.  To start out with, each gene/protein would already need a systematic functional mapping.  This could be as simple as running InterProScan on every protein, expanded to find Orthogroups (or OrthoMCL orthologs) and transfer function from model systems, and finally even more advanced, do further classified better with tools like SIFTER.

Interlinked with these orthologous and paralogous gene sets would be anchors for analyses of chromosomal synteny and even comparative assembly including tools like Mercator.  Certainly things like all of this exist but making it more pluggable for different sets of species would be an important additional component.

At a utility level, the gene annotation and functional mapping of all this information should be possible. I would imagine a researcher could upload the sequence assembly they received from the core facility and the system can generate multiple gene predictions, annotate the genes, and link these genes within the known orthogroups of the system (preserving their privacy for these genes if desired).  Presumably this sort of thing would be easier as a standalone in-house for the researcher, but web services could also be the place for this.

For fungal-sized genomes this amount of data is not too extereme.  Things like Genome Browser, BLAST, etc should all be rolled out of the box based on the basic builds.

On the DIY and community annotation front, there would also need to be a layer of community derived annotation that could be layered on all these systems.  I would imagine this both to be for gene structure annotation (genome annotation) and functional annotation (protein X does Y based on experiment Z, here is the journal reference).  I think aspects of this would be visible, auditable (tracked), but maybe not blessed as official until a curator could oversee these inputs. In my mind, whether or not this is in a Wiki per se or just new system that allows community input is less important to me than having it be a) structured (not a bunch of free text) b) tracked and versionable c) easy for researchers to input so that the knowledge is captured, even if it has to be reorganized later on.

Seems like a lot of work to be done, but really many of these things already exist through what  the GMOD project has built.  Many loose ends and software that doesn’t fully meet up to these needs, but I think the important concept is these are all general solutions that will be of benefit to most communities, not just the fungal ones.  One lingering question I always have when approaching genomic datas

that will be dynamic, what if any of this makes its way into GenBank?  How is this sort of thing banked so that it can be captured, and does the improved functional or gene structure annotation ever make its way into the repository databases to correct and improve what has already been submitted there?

Trichoderma reesei genome paper published

TrichodermaThe Trichoderma reesei genome paper was recently published in Nature Biotechnology from Diego Martinez at LANL with collaborators at JGI, LBNL, and others. This fungus was chosen for sequencing because it was found on canvas tents eating the cotton material suggesting it may be a good candidate for degrading cellulose plant material as part of cellulosic ethanol or other biofuels production.  The fungus also has starring roles in industrial processes like making stonewashed jeans due to its prodigious cellulase production.

The most surprising findings from the paper include the fact that there are so few members of some of the enzyme families even though this fungus is able to generate enzymes with so much cellulase activity. The authors found that there is not a significantly larger number of glucoside hydrolases which is a collection of carbohydrate degrading enzymes great for making simple sugars out of complex ones. In fact, several plant pathogens compared (Fusarium graminearum and Magnaporthe grisea) and the sake fermenting Aspergillus oryzae all have more members of this family than does.  T. reesei has almost the least (36) copies of a cellulose binding domain (CBM) of any of the filamentous ascomycete fungi.  They used the CAZyme database (carbohydrate active enzymes) database which has done a fantastic job building up profiles of different enzymes involved in carhohydrate degradation binding, and modifications.

Whether T. reesei is really the best cellulose degrading fungus is definitely an open question.  That it works well in the industrial culture that it has been utilized in is important, but there may be other species of fungi with improved cellulase activity and who may in fact have many more copies of cellulases.  So it will be good to add other fungi to the mix with quantitative information about degradation to try and glean what are the most important combination of enzymes and activities.

One technical note.  The comparison of copy number differences employed in the paper is a simple enough Chi-Squared, work that I’ve done with Matt Hahn and others include a gene family size comparison approach that also taked into account phylogenetic distances and assumes a birth-death process of gene family size change.  It would be great to apply the copy number differences through this or other approaches that just evaluate gene trees for these domains to see where the differences are significant and if they can be polarized to a particular branch of the tree.

So will this genome sequence lead to cheaper, better biofuel production? Certainly it provides an important toolkit to start systematically testing individual cellulase enzymes. It’s hard to say how fast this will make an impact, but the work of JBEI and a host of other research groups and biotech companies are going to be able to systematically test out the utility of these individual enzymes.

There is also evolutionary work by other groups on the evolution of these Hypocreales fungi trying to better define when biotrophic and heterotrophic transitions occurred to sample fungi with different lifestyles that might have different cellulase enyzmes that may not have been observed. Defining the relationships of these fungi and when and how many times transitions to lifestyles occurred to choose the most diverse fungi may be an important part of discovering novel enzymes.

Also see

Martinez, D., Berka, R.M., Henrissat, B., Saloheimo, M., Arvas, M., Baker, S.E., Chapman, J., Chertkov, O., Coutinho, P.M., Cullen, D., Danchin, E.G., Grigoriev, I.V., Harris, P., Jackson, M., Kubicek, C.P., Han, C.S., Ho, I., Larrondo, L.F., de Leon, A.L., Magnuson, J.K., Merino, S., Misra, M., Nelson, B., Putnam, N., Robbertse, B., Salamov, A.A., Schmoll, M., Terry, A., Thayer, N., Westerholm-Parvinen, A., Schoch, C.L., Yao, J., Barbote, R., Nelson, M.A., Detter, C., Bruce, D., Kuske, C.R., Xie, G., Richardson, P., Rokhsar, D.S., Lucas, S.M., Rubin, E.M., Dunn-Coleman, N., Ward, M., Brettin, T.S. (2008). Genome sequencing and analysis of the biomass-degrading fungus Trichoderma reesei (syn. Hypocrea jecorina). Nature Biotechnology DOI: 10.1038/nbt1403

Comparing development

PZ Meyers has a post summarizing of an older paper from Elliot Meyerowitz (2002) that comapares plant and animal development. In particular there is are some major themes summarized about how plants and animals form patterns and cell to cell signaling as part of development. What’s missing is what we’ve learned about within group comparisons where there are multiple lineages of single-celled and multicelled forms like choanozoa/metazoa (See M. brevicolis genome paper) and green algae (VolvoxChlamydomonas comparisons are forthcoming, but see Chlamydomonas genome paper).

I hope some of our work will provide more data to include in the comparison of fungal, animal, and plant development in the not too distant future.

Phytopathogenic Fungi: what have we learned from genome sequences?

ResearchBlogging.orgA review in Plant Cell from Darren Soanes and colleagues summarizes some of the major findings about evolution of phytopathogenic fungi gleaned from genome sequencing highlighting 12 fungi and 2 oomycetes. By mapping evolution of genes identified as virulence factors as well as genes that appear to have similar patterns of diversification, we can hope to derive some principals about how phytopathogenic fungi have evolved from saprophyte ancestors.

They infer from phylogenies we’ve published (Fitzpatrick et al, James et al) that plant pathogenic capabilities have arisen at least 5 times in the fungi and at least 7 times in the eukaryotes. In addition they use data on gene duplication and loss in the ascomycete fungi (Wapinski et al) to infer there large numbers of losses and gains of genes have occurred in fungal lineages.

Continue reading Phytopathogenic Fungi: what have we learned from genome sequences?

Sex in fungi: MAT locus cloned from a Zygomycete

On the cover of this week’s Nature is a picture of Phycomyces blakesleeanus Nature Coverhighlighting the discovery of the MAT locus in this Zygomycete fungus from Alex Idnurm and Joe Heitman and colleagues. While it was previously known that Zygomycetes (the Orange lineage represented by R. oryzae in the tree below) mate, the specific locus has until now, never been discovered. The authors in this study identified the MAT locus through a sequence search looking for HMG-box genes knowing that these are found the Mating Type locus in Basidiomycetes and Ascomycetes. They confirmed the identity through a through set of experiments that included PCR, sequencing and crosses of (+) and (-) strains of P. blakesleeanus, and Southern blots.

Continue reading Sex in fungi: MAT locus cloned from a Zygomycete

Willi Hennig Superstar

Willi HennigThe Willi Hennig Society, homebase for all good cladists, has subsidized the license fee for TNT so that it is now a freely available program (although it is not open-source). TNT implements phylogenetic analysis under parsimony with a fast tree searching algorithm. I believe TNT was one of the software tools that CIPRES was targeting for optimization as well so this may reflect some of that work.

From EvolDir.

Evolutionary morphology of mushroom-forming fungi

Blogging about Peer-Reviewed ResearchDave Hibbett wrote a great article for Mycological Research that describes the current state of systematics and evolutionary studies of morphology in mushroom-forming Agaricomycete fungi. His article, dedicated to the late, great mycologist Orson K Miller, Jr and entitled “After the gold rush, or before the flood? Evolutionary morphology of mushroom-forming fungi (Agaricomycetes) in the early 21st century” describes the how classification and systematics has changed in the last two hundred years and macromorphology to the more than “108,000 nucleotide sequences of ‘homobasidiomycetes’, filed under 7300 unique names.”

The article contains some beautiful pictures many of which are taken from some of the eminent mycological photographers and mycologists Michael Wood and Taylor Lockwood.

Continue reading Evolutionary morphology of mushroom-forming fungi

Saccharomyces strain sequencing

Blogging on Peer-Reviewed ResearchWhile many strains of S. cerevisiae are being sequenced, a single strain, YJM789, isolated from the lung of an AIDS patient was sequenced a few years ago at Stanford and published this summer. The genome was described in a paper entitled “Genome sequencing and comparative analysis of Saccharomyces cerevisiae strain YJM789”.

Continue reading Saccharomyces strain sequencing

This fungus will trap you (if you are a Nematode)

Blogging about Peer-Reviewed ResearchFungi, like most organisms, take an active role in finding food for survival. When thinking about hostile takeovers by fungi, one probably thinks about mycelia growing towards nutrients, rotting plant matter, the ability to extract nutrients from a living host, or perhaps producing toxins or secondary metabolites that can affect the host. However, some fungi can take an even more active role and trap their animal hosts (when that animal isn’t much bigger than you). A paper from earlier this year on “Evolution of nematode-trapping cells of predatory fungi of the Orbiliaceae based on evidence from rRNA-encoding DNA and multiprotein sequences” describes the evolutionary history of a group of fungi able to trap and eat nematodes. Nematode trapping fungi have been investigated experimentally since at least the 30s (Drechsler, Mycologia. 1937, Drechsler, J Wash Acad Sci. 1933), and some more recent studies of the relationship of the groups (Rubner, Studies in Mycology. 1996).

In the recent PNAS paper, the authors used multi-locus sequencing to reconstruct a phylogeny and history of large group of carnivorous fungi and reconstruct the ancestral history the prey trapping mechanism of either through constricting rings or adhesive traps. They were able to reconstruct the likely order of the evolutionary steps needed to make the stalk and trapping cells. They found that the most common type of trap, an Adhesive Network, was the earliest evolved trap.

Some movies also demonstrate how these fungi make their living.

Amanita toxin genes

A. bisporigeraMichigan State researchers Heather Hallen and Jonathan Walton have reportedly cloned genes from Amanita for alpha-amanitin (mispelled as alpha-aminitin in NYTimes article) which inhibits RNA polymerase II and phallacidin which inhibits actin filament polymerization. The gene sequences are in GenBank for those itching to look at evolutionary relationships of these genes in other fungi.

This is unfortunately another annoying example of science-by-press release where the PNAS publication is not available but the press release and NYtimes article are, but that shouldn’t take aware from a cool result. We also had to wait a week after the dandruff genome announcement to read that paper, I hope the PNAS press-release publication-release timeline gets synchronized soon…

Update: Gene family encoding the major toxins of lethal Amanita mushrooms manuscript is available now.

A writeup about the A. bisporigera “destroying angel” shown here can be read at the Cornell Mushroom blog and the deadly consequences of ingesting it.

[Thanks ShannonS via FredS]