Category Archives: saccharomyces

Postdoc: Yeast evolutionary genomics, UW Madison

Chris Hittinger at UW Madison is seeking a highly motivated postdoctoral researcher with an exceptional background in bioinformatics, functional genomics, or evolutionary genomics. Experience analyzing Illumina sequence data, computer programming proficiency, and training in ecological or evolutionary genetics are highly desirable.

The lab has recently received generous funding for yeast
evolutionary genomics research from the National Science
Foundation¢s Dimensions of Biodiversity Program
and the Pew Charitable Trusts

With Antonis Rokas (Vanderbilt) and Cletus P. Kurtzman (USDA), the Y1000+ Project ( seeks to sequence and analyze the to complete genomes of all ~1,000 known species of Saccharomycotina yeasts and determine the genetic basis of their metabolic, ecological, and functional diversification. Yeasts are genetically more diverse than vertebrates and have remarkable metabolic dexterity, but most remain minimally characterized. They compete vigorously for nutrients in every continent and biome and can produce everything from beer to oil. The history of yeasts is recorded in their genome sequences. Now is the time to read it and tell their story!

The Hittinger Lab has diverse funding for other basic and applied research from NSF, DOE, and USDA, but we are specifically expanding our basic research in ecological and evolutionary genomics.

The complete advertisement and application instructions can be found here:

The precise start date is flexible, but candidates should apply by November 30th to receive full consideration.


Chris Todd Hittinger, Assistant Professor of Genetics
Genome Center of Wisconsin
J. F. Crow Institute for the Study of Evolution
University of Wisconsin-Madison
425-G Henry Mall, 2434 Genetics/Biotechnology Center
Madison, WI 53706-1580, (608) 890-2586

A cacophony of comparative genomics papers

A nice series of comparative genomics articles have been published in the last few weeks. The pace of genome sequencing has accelerated to the point that we have lots of sequencing projects coming from individual labs and small consortia not necessarily from genome centers. We are seeing a preview of what next (2nd) generation sequencing will enable and can start to imagine what happens when even cheaper 3rd generation sequencing technologies are applied. I’m behind in reviewing these papers for you, dear reader, but I hope you’ll click through and take a look at some of these papers if you are interested in the topics.

In the following set of papers we have some nice examples of comparative genomics of closely related species and among a clade of species. The papers mentioned below include our work on the human pathogens Coccidioides and Histoplasma (Sharpton et al) studied at several evolutionary distances, a study on Saccharomycetaceae (Souciet et al) clade of yeast species, and a comparison of two species of Candida (Jackson et al): the commensal and opportunistic fungal pathogen Candida albicans with a very closely related species Candida dubliensis.  There is also a nice comparison of strains of Saccharomyces cerevisiae looking at effects of domestication and examples of horizontal transfer.

There is also a report of de novo sequencing of a filamentous fungus using several approaches, traditional Sanger sequencing, 454, and Illumina/Solexa (DiGuistini et al).

Finally, a paper from a few months ago (Ma et al), gives a fantastic look at one of the early branches in the fungal tree – the Mucorales (formerly Zygomycota) – via the genome of Rhizopus oryzae.  This paper is a really excellent example of what we can learn about a group of species by contrasting genomic features in the early branches in the tree with the more well studied Ascomycete and Basidiomycete fungi.  More genome sequences will help us build on these findings and clarify if some of the observations are unique to the lineage or universal aspects of the earliest fungi.

I hope you enjoy!

Novo, M., Bigey, F., Beyne, E., Galeote, V., Gavory, F., Mallet, S., Cambon, B., Legras, J., Wincker, P., Casaregola, S., & Dequin, S. (2009). Eukaryote-to-eukaryote gene transfer events revealed by the genome sequence of the wine yeast Saccharomyces cerevisiae EC1118 Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0904673106 (via J Heitman)

Jackson, A., Gamble, J., Yeomans, T., Moran, G., Saunders, D., Harris, D., Aslett, M., Barrell, J., Butler, G., Citiulo, F., Coleman, D., de Groot, P., Goodwin, T., Quail, M., McQuillan, J., Munro, C., Pain, A., Poulter, R., Rajandream, M., Renauld, H., Spiering, M., Tivey, A., Gow, N., Barrell, B., Sullivan, D., & Berriman, M. (2009). Comparative genomics of the fungal pathogens Candida dubliniensis and C. albicans Genome Research DOI: 10.1101/gr.097501.109

DiGuistini, S., Liao, N., Platt, D., Robertson, G., Seidel, M., Chan, S., Docking, T., Birol, I., Holt, R., Hirst, M., Mardis, E., Marra, M., Hamelin, R., Bohlmann, J., Breuil, C., & Jones, S. (2009). De novo genome sequence assembly of a filamentous fungus using Sanger, 454 and Illumina sequence data. Genome Biology, 10 (9) DOI: 10.1186/gb-2009-10-9-r94 (open access)

Sharpton, T., Stajich, J., Rounsley, S., Gardner, M., Wortman, J., Jordar, V., Maiti, R., Kodira, C., Neafsey, D., Zeng, Q., Hung, C., McMahan, C., Muszewska, A., Grynberg, M., Mandel, M., Kellner, E., Barker, B., Galgiani, J., Orbach, M., Kirkland, T., Cole, G., Henn, M., Birren, B., & Taylor, J. (2009). Comparative genomic analyses of the human fungal pathogens Coccidioides and their relatives Genome Research DOI: 10.1101/gr.087551.108 (open access)

Souciet, J., Dujon, B., Gaillardin, C., Johnston, M., Baret, P., Cliften, P., Sherman, D., Weissenbach, J., Westhof, E., Wincker, P., Jubin, C., Poulain, J., Barbe, V., Segurens, B., Artiguenave, F., Anthouard, V., Vacherie, B., Val, M., Fulton, R., Minx, P., Wilson, R., Durrens, P., Jean, G., Marck, C., Martin, T., Nikolski, M., Rolland, T., Seret, M., Casaregola, S., Despons, L., Fairhead, C., Fischer, G., Lafontaine, I., Leh, V., Lemaire, M., de Montigny, J., Neuveglise, C., Thierry, A., Blanc-Lenfle, I., Bleykasten, C., Diffels, J., Fritsch, E., Frangeul, L., Goeffon, A., Jauniaux, N., Kachouri-Lafond, R., Payen, C., Potier, S., Pribylova, L., Ozanne, C., Richard, G., Sacerdot, C., Straub, M., & Talla, E. (2009). Comparative genomics of protoploid Saccharomycetaceae Genome Research DOI: 10.1101/gr.091546.109 (open access)

Ma, L., Ibrahim, A., Skory, C., Grabherr, M., Burger, G., Butler, M., Elias, M., Idnurm, A., Lang, B., Sone, T., Abe, A., Calvo, S., Corrochano, L., Engels, R., Fu, J., Hansberg, W., Kim, J., Kodira, C., Koehrsen, M., Liu, B., Miranda-Saavedra, D., O’Leary, S., Ortiz-Castellanos, L., Poulter, R., Rodriguez-Romero, J., Ruiz-Herrera, J., Shen, Y., Zeng, Q., Galagan, J., Birren, B., Cuomo, C., & Wickes, B. (2009). Genomic Analysis of the Basal Lineage Fungus Rhizopus oryzae Reveals a Whole-Genome Duplication PLoS Genetics, 5 (7) DOI: 10.1371/journal.pgen.1000549 (open access)

Sequencing wine spoilage yeast

There is an article in Wine Spectator (Seen on the JGI feed) on sequencing the wine spoilage yeast bruxellensis (correct name is now Dekkera bruxellensis) which adds the not-so-excellent taste of “sweaty horse” to wines.  There is already some survey sequencing done by Ken Wolfe and Jurge Piskur’s groups so a full genome sequencing project will help work out how this yeast is able to out compete Saccharomyces and cause dramatic wine spoilage.  This is also relevant on the bio-fuel side since this yeast can also taint an ethanol bio-reactor.  It is an interesting ecology inside the wine bottle and this competition for resources can lead to bad tasting wine. The competition presumably originated in some form in the rotting fruit where these yeasts compete for space and use different approaches in their niche including the fermentation process which produces the revered ethanol by-product and helps establish a chemical-warfare driven landgrab.  The ethanol also helps prevent and of course this has implications for the Drosophila (Sophophora) flies that land there and eat yeast. They needed a good way to overcome the ethanol like the well studied Adh gene.

Yeast population genomics
I have cheered the Sanger-Wellcome SGRP group work to generate multiple Saccharomyces cerevisiae and S. paradoxus strain genome sequences.   The group had previously submitted a version of the manuscript to Nature precedings and it is now published in Nature AOP showing that submitting to a preprint server doesn’t necessarily hurt your manuscript getting published…  The research groups explored the impact of domestication (as was also recently done for the sake and soy sauce worker fungus, Aspergillus oryzae) on the Saccharomyces genome by comparing individuals from wild strains of S. paradoxus.

This paper addressed several challenges including methodology for light genome sequencing for population genomics. This data represents in a way, a pilot project on for genome resequencing projects and using draft genome sequencing with next generation sequencing tools. Of course with the pace of sequencing technology development, any project more than a couple months old will be using outdated technology it seems, but this work represents some important progress.  Tools like MAQ were also developed and tuned as part of the project.  In addition to the methods development it also provided a new look at evolutionary dynamics of a well-studied fungus.

Genome assembly
The authors apply several different quality controls and utilize a new tool called PALAS (Parallel ALignment and ASsembly)  to assemble all the strains at the same time using a graph-based approach that utilized the reference genome sequences for each species. This is different than a full-blown WGA approach like PCAP, Phusion or Arachne because this is deliberately low-coverage sequencing pass.  The authors are trying impute missing sequence via Ancestral Recombination Graphs as implemented in the Margarita system.   They also use MAQ to align sequence from Illumina/Solexa sequencing to these assemblies made by PALAS.

Since this project was on two species of SaccharomycesS. cerevisiae and S. paradoxus they needed good reference assemblies for each of these species. The previously availably S.paradoxus assembly wasn’t complete enough for this study so they did an addition 4.3 X coverage with sanger/ABI sequencing and 80X coverage with Illumina.

Population genomics and domestication

The sequencing data also provided a framework for population genetic investigations. Some simple findings showed that geographic isolates within each species were more genetically similar to each other.  The main geographic regions of samples for S.paradoxus data included the UK, American, and Far East samples, some of which had been analyzed in a very nice study on Chromosome III.  For the S. cerevisiae samples there were individuals from around Europe, at least 10 European wine strains, Malaysian, Sake brewing strains, West Africa, and North America. From these data it was possible to discover that there are several of strains with mosiac genomes meaning that pieces of the genome match best with the sake fermentation strains and other parts from the wine/European samples.

Efforts to detect the effects of natural selection that may be linked to domestication of these strains explored two different approaches. The McDonald-Kreitman test did not identify any loci under positive selection while Tajima’s D was negative in the S.cerevisiae global and wine strain populations indicating an excess of singleton polymorphisms – though they draw little conclusions from that.  The authors also observed a sharper decay of linkage disequilibrium in S.cerevisiae (half maximum of 3kb) than S.paradoxus (half maximum 9kb) suggesting that S.cerevisiae is recombining more, either due to increased opportunities or a great frequency of recombination events when it does.

In context of the paper title and the idea of exploring the effects of domestication on the genome, the authors observe that the standard paradigm that ‘domesticated’ species have lower diversity levels is simply not the case in these samples.  This isn’t to say there isn’t evidence of the selection for fermentation production from these strains based on the stress response conditions they were tested on, but that there is still ample evidence of maintaining diversity within the populations presumably through various amounts of outcrossing.

We are also interested in these results as we apply similar questions to population genomics of the human pathogenic fungus Coccidioides where 14 strains have been sequenced with sanger sequencing technology.  Hopefully some of these lessons will resonate in our analyses and also that this era of population genomics will see ever more extensive collections to address aspects of migration, phylogeography, and local adaptations within populations of fungi and other microbes.

Gianni Liti, David M. Carter, Alan M. Moses, Jonas Warringer, Leopold Parts, Stephen A. James, Robert P. Davey, Ian N. Roberts, Austin Burt, Vassiliki Koufopanou, Isheng J. Tsai, Casey M. Bergman, Douda Bensasson, Michael J. T. O’Kelly, Alexander van Oudenaarden, David B. H. Barton, Elizabeth Bailes, Alex N. Nguyen, Matthew Jones, Michael A. Quail, Ian Goodhead, Sarah Sims, Frances Smith, Anders Blomberg, Richard Durbin, Edward J. Louis (2009). Population genomics of domestic and wild yeasts Nature DOI: 10.1038/nature07743

Monophyly of Taphrinomycotina

A recent paper in MBE  presents evidence that the Taphrinomycota (containing S. pombe and Pneumocystis) are in fact a monophyletic group. This is considered an early branch in the Ascomycota with the Pezizomycotina (filamentous ascomycete fungi like Neurospora and Aspergillus) and Saccharomycotina (fungi mainly with yeast forms including Candida and Saccharomyces).  The monophyly of Taphrinomyoctina fungi is something that has been fairly accepted but there are a few publications reporting  conflicting evidence in some sets gene trees. This conflict is most likely due to Long Branch Attraction (LBA) and the Philippe lab has long worked on this problem of LBA working to develop tools like PhyloBayes that attempt to correct for LBA with a parameter rich model and using lots of data (like whole genomes).  These authors are employing phylogenomics in the sense that multiple genes are used to reconstruct the phylogeny.  This use is different from the J.Eisen/Sjölander sense which is to infer gene function from a phylogeny.

This paper presents evidence using proteins of 113 mitochondrial and nuclear genes and finds strong statistical support for this monophyly.  They also note that it was necessary to remove fast evolving sites from a dataset of only mitochondrial genes in order to overcome LBA artifacts that lead to Saccharomyces and S. pombe sister relationship in previous analyses.

This paper also presents work using the Pneumocystis genome sequence helps resolve its placement and eventually understanding the evolution of this pathogen.  In this tree the sister group to Pneumocystis is Schizosaccharomyces but both lineages have very long branches.  The Saitoella lineage is basal in this paper which is different from what was found with a 4 gene (AFTOL) dataset (see Figure 2). Further work sampling more genes from these Taphrina lineages will likely help resolve the intra-clade relationships.

Y. Liu, J. W. Leigh, H. Brinkmann, M. T. Cushion, N. Rodriguez-Ezpeleta, H. Philippe, B. F. Lang (2008). Phylogenomic Analyses Support the Monophyly of Taphrinomycotina, including Schizosaccharomyces Fission Yeasts Molecular Biology and Evolution, 26 (1), 27-34 DOI: 10.1093/molbev/msn221

A brief history of lager yeast

Some tasty research if you are of the set who enjoy a good pint of beer. GenomeWebNews reports on a study in Genome Research by Barbara Dunn and Gavin Sherlock at Stanford, looking at the history of lager yeast Saccharomyces pastorianus, a hybrid of S. cerevisiae and S. bayanus. Using array Comparative Genome Hybridization (aCGH) they trace the history of S. pastorianus lager strains to show that they sort into two distinct groups indicating there might have been at least two independent origins of the hybrid strain/species both derived from an ale yeast.

The CGH data also indicates there have been many genome rearrangements and aneuploidies after the hybridization providing an interesting picture of recent post-allopolyploidy changes in two independent experiments. Lots more delicious genome evolution details in the paper, so drink up!

Deep EST sequencing = RNA-Seq

The transcriptional landscape of yeast has been (further) defined with Solexa sequencing in a method deemed “RNA-Seq”, but what I would call “deep EST sequencing”.  This approach for transcriptional profiling by sequencing alone is sure to be used by many labs looking for lower and more complete ways to describe and quantitate the full population of transcripts in an organism.  

Nagalakshmi, U., Wang, Z., Waern, K., Shou, C., Raha, D., Gerstein, M., Snyder, M. (2008). The Transcriptional Landscape of the Yeast Genome Defined by RNA Sequencing. Science DOI: 10.1126/science.1158441


A lot can happen after a few drinks: Saccharomyces hybridization

We may have to reevaluate whether Saccharomyces cerevisiae alone is the species used to brew beer.  A paper from Gonzalez et al describes results from PCRRFLP comparison of 24 brewing strains identifies evidence for S. cerevisiae x S. kudriavzevii hybrids.  Although this hybridization is not unprecedented, most seem to be related to cultivated brewing or fermentation strains.  It seems that the hybrids are better able to cope with the stress associated with fermentation process.

Sacch tree

It seems these would also be a great test system for more whole genome sequencing or at least more polymorphism comparisons to try and determine the proportion of the genome that comes from different parents and estimate timing and frequency of hybridization.  It seems possible that the hybridizations are occurring multiple times in nature so are the same regions from each parental genome kept in the hybrid offspring that are selected for fitness under fermentation stress?

Gonzalez, S.S., Barrio, E., Querol, A. (2008). Molecular Characterization of New Natural Hybrids of Saccharomyces cerevisiae and S. kudriavzevii in Brewing . Applied and Environmental Microbiology, 74(8), 2314-2320. DOI: 10.1128/AEM.01867-07

New Saccharomyces resequencing assembly

SGRP LogoDavid Carter at the Sanger Centre emailed a message that new assemblies of Saccharomyces strain resequencing project have been posted including a new three-way alignment of S. bayanusS.paradoxusS.cerevisiae. This updates the Dec 2007 release.

Continue reading New Saccharomyces resequencing assembly

More updates on Saccharomyces resequencing project at Sanger

I’ve paraphrased an email sent by David Carter to folks interested in Saccharomyces resequencing project.

The latest version of the SGRP data is on the web site and ftp site. This release is somewhat provisional, and motivated more by the fact that we have a paper deadline coming up than by any claim to finality. It should be quite a bit better than what was there before, but doesn’t have a correct treatment of transposons.

You can get the data by starting here:

There is also a new version of the browser:

There are a few new features in the browser which [David] is going to document over the next couple of days.

Major new features of the data are that there should be much better consistency between alignments; Solexa/Illumina data has been incorporated for the strains that had it; and the S. paradoxus alignments are based on a new assembly that created a few weeks ago and which covers about 95% of the genome; a description is at