The Hyphal Tip: Fungal Genomes and Comparative Genomics

We're excited that a Penicillium marneffei grant to Mat Fisher and collaborators has been funded by the Welcome Trust. It includes a collaboration with University College London, our lab, JCVI, and Univ of Melbourne. This project will explore functional and comparative genomics approaches to studying the fungus

The [[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 production.

The genome of Podospora anserina S mat+ strain was sequenced by Genoscope and CNRS and published recently in Genome Biology. The genome sequence data has been available for several years, but it is great to see a publication describing the findings.  The 10X genome assembly with ~10,000 genes provides an important dataset for comparisons

Researchers from Technical University of Denmark published some interesting results from comparing expression across the very distinct Aspergillus species.

Kudos also goes to making it Open Access. I am posting a few key figures below the fold because I can! They grew the fungi in bioreactors fermenting glucose or xylose. After calibrating the growth curves they were able to sample the appropriate time points for comparison of gene expression across these three species. They found a set of genes commonly expressed.

I've been too busy to post much these last few days, but here are a few links to some papers I found interesting in my recent browsing.

• FOLy: an integrated database for the classification and functional annotation of fungal oxidoreductases potentially involved in the degradation of lignin and related aromatic compounds - so a database of these enzymes

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

Webb, C.J., Zakian, V.A. (2008). Identification and characterization of the Schizosaccharomyces pombe TER1 telomerase RNA. Nature Structural & Molecular Biology, 15(1), 34-42. DOI: 10.1038/nsmb1354

Leonardi, J., Box, J.A., Bunch, J.T., Baumann, P. (2008). TER1, the RNA subunit of fission yeast telomerase. Nature Structural & Molecular Biology, 15(1), 26-33. DOI: 10.1038/nsmb1343

Two papers in Nature Structural & Molecular Biology identify the telomerase RNA in Schizosaccharomyces pombe. Telomerase is a multi-unit enzyme that has both protein and RNA components. While the protein subunit is highly conserved and identifiable through sequence comparisons of eukaryotes, the RNA subunit has a variable size and sequence making identification through comparative means more difficult. The S. pombe telomerase RNA subunit, or TER1, was discovered by two labs applying similar biochemical approaches to identify the locus.

Dave 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.

While 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". The authors find a few notable rearrangements and unique genes in this strain as compared to the lab and type strain S288C. They find examples of horizontally transferred genes or potentially genes (like RTM1) which are being exchanged among individuals in the population and just not found in first sequenced strain. There are several other genome architecture observations including numbers of indels and highly polymorphic (and thus different from S288C) ORFs. In general the chromosomes are co-linear but they find some rearrangements. One of the main trains of a human pathogenic fungi, which some people will argue aren't really pathogenic since the host must be severely immunocompromised to infect, is the ability to grow at high or body (37 C) temperatures. Most fungi can't survive at this temperature, but this trait is a necessary condition for fungi like Cryptococcus neoformans, Aspergillus fumigatus, and the pathogenic Candida species like C. albicans to infect and potentially overwhelm a host. Previous work from many of the same authors used a QTL approach to map the high temperature phenotype in a clinical strain Saccharomyces using a new genetic technique called reciprocal-hemizygosity to dissect the QTL. This is only the second actual publication of the genome of another strain of Saccharomyces cerevisiae even though there have been several papers profiling rates of evolution in the lab and wild strains S288C, YJM789, and RM11-1A (Gu 2005, Ronald et al 2006) before the final genome paper was published. I doubt we'll keep seeing papers about a single strain sequenced when there is already a reference strain. Instead papers about clusters of strains or closely related species such nearly complete work in other Saccharomyces strains, Coccidioides and Neurospora will probably be the norm. This paper is available as Open Access through PNAS which I applaud the authors for. However, the paper concludes with a paragraph that starts

"Finally, we made the YJM789 genome a free-to-access resource that marks an initial step toward a more complete set of reference sequences for the S. cerevisiae species"

While I am happy to see the sequence resource freely available now, I guess I've come to expect this with any genome publication. The sequence has been available with some restrictions at least since 2003 before the genome was published in a journal. I am unsure why this needs to be championed in the conclusion, shouldn't it be available as a consequence of how it was funded or am I expecting too much?

"This work was supported by National Institutes of Health Grants HG02052 (to R.W.D.), GM068717 (to R.W.D. and L.M.S.), and HG000205 (to R.W.D. and L.M.S.);"

There is more discussion of the project and its future at the Stanford site.

Reverting CUG tRNA from derived change coding for serine back to leucine (standard code) has profound effect on organism.