Lichen genome projects and the power shift prompted by next-gen sequencing

Genome Technology highlights the very cool thing about next-gen sequencing – it puts the power in the hands of the researchers to explore genome sequence and doesn’t limit them to projects only funded through sequencing centers. The Genome Technology piece highlights work at Duke to sequence the genome Cladonia grayi, a lichenized fungus, with 454 technology at Duke’s Institute for Genome Sciences and Policy through their next-gen sequencing program. This is the way of the future where sequencing core facilities will be able to generate sequence only having to wait in the queue at the own university rather than through community sequencing project or sequencing center proposal queues.

This isn’t the only lichen being sequenced. Xanthoria parietina is also in the queue at JGI, but has taken a while to get going because of some logistical problems getting the DNA (and any problems are amplified because it takes a long time to get new material since lichens grow very slow).

The transfer of the power for researchers to be able to quick exploratory whole-genome sequencing with next-gen and eventually, high quality genome sequences from next-gen sequencing is predicted to transform how this kind of science gets done. It means we’ll probably just sequence a mutant strain instead of trying to map the mutation – this is happening already in anecdotal stories in worms and in our work in mushrooms. N.B. this is done after a mutagenized strain has been cleaned up a bit to insure we’re looking for one or only a few mutations based on some crosses – but that is part of standard genetic approaches anyways.

This fast,cheap,whole-genome-sequencing is also the stuff of personal genomics, but for basic research it will also mean that a first pass exploring gene repertoire of an organism will be a multi-week instead of multi-year project. I just hope we’re training enough people who can efficiently extract the information from all this data with solid bioinformatics, computational, data-oriented programming, and statistical skills to support all the labs that will want to take this approach. You’ll need a life-vest to swim in the big data pool for a while until more tools are developed that can be deployed by non-experts.

Bat White-nose syndrome brevia

A Brevia piece in Science today describes efforts to describe the causal agent in white-nose syndrome (WNS) in bats which appears to be contributing to bat decline. According to the authors, previous work had described an uncharacterized fungus associated with bats that showed signs of being sick with WNS. This is an emerging pathogen as the samples described in this paper were from Spring 2008. Phylogenetic analysis of the rDNA (and presumably ITS) sequence of fungal isolates from diseased bats placed it as a Geomyces spp, in the Helotiales order (in the Leotiomycetes if you are wondering what are the closest sequenced fungal genomes for this species). Other Geomyces spp are also psychrophiles and found colonizing the skin of animals in cold climates (it must be hard to make a living). The authors suggest the finding of this fungal species on bats is consistent with its involvement in disease. The authors also make the parallel to chytridiomycosis, an emerging pathogen of amphibians that is contributing to the worldwide amphibian decline.

This is just the first of hopefully several publications studying this phenomenon as this brief piece sets the stage for additional questions. It is not yet been shown that this fungus is actually causing the disease, i.e. satisfying Koch’s postulates, and isn’t just a canary in the coal mine. So-called opportunistic fungi like Aspergillus fumigatus, Cryptococcus neoformans, and Candida albicans cause infections that emerge after the patient’s immune system has been compromised by something else such as HIV or immunosuppressant drugs as part of an organ transplant regime. It is possible that the white-nose syndrome (ie white conidia from Geomyces sp is just a manifestation of an infection of a commensal organism like thrush or yeast infections of Candida albicans that only emerge when something else has knocked down the host’s immune system. I don’t know if this same Geomyces sp can be cultured from healthy bats from so-far uninfected colonies which would suggest the fungus is present all the time.

As we track and learn more about natural die-offs and disease in animals from infectious diseases there are series of recent fungal-associated disease of animal populations including honeybees perhaps from a virus and a microsporidium, frogs and amphibians via Batrachochytrium dendrobatidis, and white-nose syndrome. Diseases like Cryptococcus gattii are also examples of pathogens that may be able to infect healthy animals and humans. It seems quite important to know more important to track and study how these outbreaks spread and the evolutionary and ecological basis for the sudden rise in infection and mortality in animal populations to understand diseases of human relevance as well.

Related links:

D. S. Blehert, A. C. Hicks, M. Behr, C. U. Meteyer, B. M. Berlowski-Zier, E. L. Buckles, J. T. H. Coleman, S. R. Darling, A. Gargas, R. Niver, J. C. Okoniewski, R. J. Rudd, W. B. Stone (2008). Bat White-Nose Syndrome: An Emerging Fungal Pathogen? Science DOI: 10.1126/science.1163874

Jobs in fungal genomics

Trying a little experiment here. I’ve started a wiki page for jobs that fall into the general category of genomics, fungi, and evolution and added a tab link to this at the top of the blog site. At this point I am only posting academic positions (Faculty and postdoctoral positions) but it may be possible to include industry and government postings if there is sufficient interest.

You are welcome to sign up for a wiki account and add links for other positions.

Registration opens for 25th Fungal Genetics

FG25 LogoRegistration opens today for the 25th Fungal Genetics conference at Asilomar. The preliminary program is also available with a great slate of speakers already lined up and plenty of opportunity for many students and postdocs to present their work.

The 24th conference help in 2007 was great and expect a similar great opportunity for sharing science and networking with the fungal genetics community.

Related links

Removing sulfur from crude oil via Stachybotrys

Nature news picked up an article that a Stachybotrys sp. can remove sulfur from crude oil and which would be more efficient than traditional chemical and heat methods. You may remember that some Stachybotrys are a nasty black indoor mold that can cause indoor air quality problems. It will be quite interesting to see more about this particular species once it has been better followed up.

Fungal P450s

A paper (Park et al, BMC Genomics) from Fungal Bioinformatics Lab at Seoul University in South Korea describes their new “Fungal P450 Database”. The database contains sequence, names, and genome links for P450’s (or Cytochrome P450s) identified by similarity and phylogenetic classification from genome annotations.  The group is using most of annotated genomes in GenBank (and I think some from elsewhere) of bacterial, fungi, animals, and plants.

I find the current nomenclature for this family of genes confusing but it has been I am sure a difficult job and wrangled to a large part by David Nelson (who also has a new paper on the CYPome of Aspergillus nidulans). I have found it difficult to follow the logic for naming these members, as it didn’t seem to be particularly phylogenetic at first, although I think that has improved. However, a stable and solid reference database is needed to for naming these gene members and for mapping new members in through straightforward analyses is an essential resource. Park et al have made great inroads to that end and it may indeed meet needs (I am cautious to say it is solved without more exploration or some sense of whether it is intended or will be taken up as just that sort of reference by the P450 community).  It has seemed to me that a proper phylogenetic (or really, a phylogenomic) approach is essential for naming the P450 member genes as orthologous or paralogous members across multiple species. The group has defined their classes as clusters of homologs (e.g. Mg004 is Magnaporthe grisea gene in Cluster 9.1) and linked these also to the Nelson nomeclature (CYP68E1).  By defining orthologous family members we can make more interpretations about how to transfer functional annotation in a truly phylogenomic context. 

The overall family is so large and diverse (they report 4538 fungal P450s into 141 clusters/sub-families from 68 species) across many different species. The fungi tend to have very large families in some clades (e.g. some filamentous fungi) so I think this type of systematic and searchable system that will have stable identities for clusters is an essential resource. I know I’m going to try and give it a whirl. We have a couple of cool findings about changes in the P450 families in Basidiomycete Coprinopsis and related species comparisons that I hope we’ll be able to better interpret with this additional phylogenomic naming of gene family members.

Jongsun Park, Seungmin Lee, Jaeyoung Choi, Kyohun Ahn, Bongsoo Park, Jaejin Park, Seogchan Kang, Yong-Hwan Lee (2008). Fungal cytochrome P450 database BMC Genomics, 9 (1) DOI: 10.1186/1471-2164-9-402