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Genome Evolution in Yeast Species
We are interested in genome evolution in eukaryotes, and have chosen the yeasts (unicellular ascomycete fungi) as a primary system to work on. Yeasts are an ideal system to study because their genomes are small (~12 Mbp) and relatively easy to sequence and annotate, and because the available genome sequences span a range of divergence levels: from very closely-related pairs of species whose genomes are almost colinear, to highly diverged pairs of species whose genomes show very little conservation of gene order along chromosomes.

In 1997 we discovered that the bakers' yeast Saccharomyces cerevisiae is an ancient polyploid, having undergone a whole-genome duplication (WGD) approximately 100 Mya [1]. This was the first time an ancient polyploidization had been detected by bioinformatic analysis of a genome sequence. Subsequently we focused on the evolutionary implications of the WGD, including the way in which the deletion of genes from polyploid genomes can cause passive reproductive isolation between lineages [2]. We sequenced the genome of Kluyveromyces polysporus, a species that diverged from the S. cerevisiae lineage very soon after the WGD when the process of gene loss had just begun [3].

In 2005 we developed the Yeast Gene Order Browser (YGOB) as a way of visualizing and curating the synteny relationships among sequenced yeast genomes [4]. YGOB enables us to identify orthologs, detect evolutionary rearrangements of gene order, and infer the ancestral content and structure of the genome at the time of WGD.

Our current research projects are focused on these areas:

Gene gain and loss
What genes have been added to, or lost from, yeast genomes during their recent past? For recently added genes and gene families, where did they come from? How do they diversify?

Orphan genes (see [5])
Orphans are real genes that exist in one species but appear not to have homologs in other species. What are these things? Are they recently evolved genes? Are they genes that are evolving so fast that their orthologs have become undetectable? Can we use them to improve bioinformatics methods of remote homolog detection?

Gene order evolution (see [6])
Does it matter where a gene resides on a chromosome? Do genes ever transpose to new genomic locations, or are all apparent transpositions the result of short-lived duplications?

Evolution of the yeast MAT locus system (see [7])
How did the mating-type switching system used by S. cerevisiae originate? What existed before it? How has the MAT-containing chromosome evolved? Where did the SIR silencing system come from?


Hobby projects
Paleopolyploidization in eukaryotes you can't make beer from. Such as Xenopus [8], or the ancient 2R duplications in vertebrates [9], or a zillion WGDs in plants [10].

PubCrawler. Our free service for alerting you about new papers in PubMed (and new DNA sequences in GenBank) relevant to your interests has been running automatically for a decade and now has over 40,000 users. See its website at www.pubcrawler.ie.

Chloroplast genome evolution. Some habits just can't be kicked [11,12].


Research opportunities
We're a bioinformatics lab working on genome evolution. We run programs, not gels, though we sometimes collaborate with wet labs or use commercial companies to do DNA sequencing. We regularly have research opportunities for postdocs with either of these backgrounds:

- Experience in computational molecular evolution, including computer programming.
- Experience in yeast biochemistry/genetics and an interest in moving into bioinformatics/ molecular evolution.


References
[1] Wolfe, K.H. and Shields, D.C. (1997). Molecular evidence for an ancient duplication of the entire yeast genome. Nature 387, 708-713.
[2] Scannell, D.R.*, Byrne, K.P.*, Gordon, J.L., Wong, S. and Wolfe, K.H. (2006). Multiple rounds of speciation associated with reciprocal gene loss in polyploid yeasts. Nature 440, 341-345.
[3] Scannell, D.R., Frank, A.C., Conant, G.C., Byrne, K.P., Woolfit, M. and Wolfe, K.H. (2007). Independent sorting-out of thousands of duplicated gene pairs in two yeast species descended from a whole-genome duplication. Proc Natl Acad Sci U S A 104, 8397-8402.
[4] Byrne, K.P. and Wolfe, K.H. (2005). The Yeast Gene Order Browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res 15, 1456-1461.
[5] Wolfe, K.H. (2006). Comparative genomics and genome evolution in yeasts. Philos Trans R Soc Lond B Biol Sci 361, 403-412.
[6] Wong, S. and Wolfe, K.H. (2005). Birth of a metabolic gene cluster in yeast by adaptive gene relocation. Nature Genetics 37, 777-782.
[7] Butler, G., Kenny, C., Fagan, A., Kurischko, C., Gaillardin, C. and Wolfe, K.H. (2004). Evolution of the MAT locus and its Ho endonuclease in yeast species. Proc Natl Acad Sci U S A 101, 1632-1637.
[8] Semon, M. and Wolfe, K.H. (2008). Preferential subfunctionalization of slow-evolving genes in Xenopus laevis. Proc Natl Acad Sci U S A 105, 8333-8338.
[9] McLysaght, A., Hokamp, K. and Wolfe, K.H. (2002). Extensive genomic duplication during early chordate evolution. Nat Genet 31, 200-204.
[10] Blanc, G. and Wolfe, K.H. (2004). Widespread paleopolyploidy in model plant species inferred from age distributions of duplicate genes. Plant Cell 16, 1667-1678.
[11] Cusack, B.P. and Wolfe, K.H. (2007). When gene marriages don't work out: divorce by subfunctionalization. Trends Genet 23, 270-272.
[12] Conant, G.C. and Wolfe, K.H. (2008). GenomeVx: simple web-based creation of editable circular chromosome maps. Bioinformatics 24, 861-862.
UNIVERSITY COLLEGE DUBLIN  |  SCHOOL OF MEDICINE  |  CONWAY INSTITUTE
© Ken Wolfe 2017