2. whole-genome duplications and large segmental duplications… …seem to be a common feature in eukaryotic genome evolution …play a crucial role in the evolution of yeasts, plants, and humans

3. whole-genome duplications and large segmental duplications… …seem to be a common feature in eukaryotic genome evolution …play a crucial role in the evolution of yeasts, plants, and humans problem: smaller changes (inversions, transpositions, gene loss, etc) makes it difficult to detect these events (synteny) problem: large segmental duplications may look like evidence of polyploidization

4. image taken from Wolfe 2001 Phylogenetic positions of some likely polyploidy events during eukaryote evolution

6. 1993: discovery of duplicated blocks of genes in the yeast genome C R Acad Sci III. 1993;316(4):367-73. Two yeast chromosomes [3, 14] are related by a fossil duplication of their centromeric regions. Lalo D, Stettler S, Mariotte S, Slonimski PP, Thuriaux P. Departement de Biologie Cellulaire et Moleculaire, C. E. A. Saclay, Bat. 142, Gif-sur-Yvette, France. J Mol Biol. 1993 Oct 5;233(3):372-88. The gene clusters ARC and COR on chromosomes 5 and 10, respectively, of Saccharomyces cerevisiae share a common ancestry. Melnick L, Sherman F. Department of Chiral Chemistry, Sepracor Inc., Marlborough, MA 01752.

7. Molecular evidence for an ancient duplication of the entire yeast genome Kenneth H. Wolfe & Denis C. Shields Department of Genetics, University of Dublin, Trinity College, Dublin 2, Ireland

8. Methods: amino acid similarity searches of all yeast proteins against one another plotting of results on dot matrices criteria for duplicated blocks: high similarity score, conservation of gene order and orientation, at least three pairs of homologs on each chromosome Results: identification of 55 duplicate regions (13% of all yeast proteins) 16%

9. Methods: amino acid similarity searches of all yeast proteins against one another plotting of results on dot matrices criteria for duplicated blocks: high similarity score, conservation of gene order and orientation, at least three pairs of homologs on each chromosome Results: identification of 55 duplicate regions (13% of all yeast proteins) Support for whole-genome duplication: for 50 of the 55 duplicate regions, the orientation of the entire block with respect to the centromere is the same in the two copies 55 duplicated regions 7 regions should be triplicated...but there are no triplicated regions. statistics 16%

10. Dating the yeast polyploidization event S. cerevisiae and Kluyveromyces diverged before the genome duplication event (based on gene order data, number of chromosomes, and phylogenetic analysis of duplicated gene sequences) S. cerevisiae and Kluyveromyces divergence: 1.5 X 10 8 years ago Mean relative age of the duplication in S. cerevisiae, relative to the speciation between S. cerevisiae and Kluyveromyces: 0.74  the genome duplication occurred roughly 10 8 years ago what was the physiology of the ancestral yeast like? retained duplicated genes before the genome duplications: were currently separate functions embodied in a single protein? did one of the two functions not exist?

12. Main conclusions: 1. there was one single duplication event 2. the duplication happened before Saccharomyces and Kluyveromyces diverged

13. Genolevures project: large scale comparative genome analysis between S. cerevisiae and 13 other hemiascomycetous yeasts FEBS Letters Volume 487/1 (December 2000) - Special Issue Editorial - Génolevures - a novel approach to `evolutionary genomics' Genomic Exploration of the Hemiascomycetous Yeasts: 1. A set of yeast species for molecular evolution studies Genomic Exploration of the Hemiascomycetous Yeasts: 2. Data generation and processing Genomic Exploration of the Hemiascomycetous Yeasts: 3. Methods and strategies used for sequence analysis and annotation Genomic Exploration of the Hemiascomycetous Yeasts: 4. The genome of Saccharomyces cerevisiae revisited Genomic Exploration of the Hemiascomycetous Yeasts: 5. Saccharomyces bayanus var. uvarum Genomic Exploration of the Hemiascomycetous Yeasts: 6. Saccharomyces exiguus Genomic Exploration of the Hemiascomycetous Yeasts: 7. Saccharomyces servazzii Genomic Exploration of the Hemiascomycetous Yeasts: 8. Zygosaccharomyces rouxii Genomic Exploration of the Hemiascomycetous Yeasts: 9. Saccharomyces kluyveri Genomic Exploration of the Hemiascomycetous Yeasts: 10. Kluyveromyces thermotolerans Genomic Exploration of the Hemiascomycetous Yeasts: 11. Kluyveromyces lactis Genomic Exploration of the Hemiascomycetous Yeasts: 12. Kluyveromyces marxianus var. marxianus Genomic Exploration of the Hemiascomycetous Yeasts: 13. Pichia angusta Genomic Exploration of the Hemiascomycetous Yeasts: 14. Debaryomyces hansenii var. hansenii Genomic Exploration of the Hemiascomycetous Yeasts: 15. Pichia sorbitophila Genomic Exploration of the Hemiascomycetous Yeasts: 16. Candida tropicalis Genomic Exploration of the Hemiascomycetous Yeasts: 17. Yarrowia lipolytica Genomic Exploration of the Hemiascomycetous Yeasts: 18. Comparative analysis of chromosome maps and synteny with Saccharomyces cerevisiae Genomic Exploration of the Hemiascomycetous Yeasts: 19. Ascomycetes-specific genes Genomic Exploration of the Hemiascomycetous Yeasts: 20. Evolution of gene redundancy compared to Saccharomyces cerevisiae Genomic Exploration of the Hemiascomycetous Yeasts: 21. Comparative functional classification of genes

14. Method: identify sequenced inserts in which two or more protein- coding genes had S. cerevisiae homologs determine order and orientation of these genes examine map conservation between S. cerevisiae and other hemiascomycetous yeasts

15. estimate global degree of conservation of synteny between S. cerevisiae and each of the other yeast species estimate frequency of single gene deletion and of frequency of gene inversion

16. in 59 out of 139 cases, the central gene of intermingled triples was inverted, i.e., the orientation was not conserved (conflicts with Wolfe & Shields conclusion)

18. Conclusions: “the major driving force of molecular evolution in eukaryotes is the continuous duplication of chromosome segments, each encompassing a few genes, that are transposed to ectopic chromosomal locations in direct or inverted orientation relative to centromeres”

20. ScienceExpress: March 4, 2004 Nature: March 7, 2004

21. taken from J Zhang, TREE 2003

22. image taken from http://www.phys.ksu.edu/gene/a2f3.html

23. polyploidization (duplication of a genome either within a species or between species) evidence for polyploidization: most or all of the genes on a given chromosome appears on another chromosome as well. problem: large segmental duplications may look like evidence of polyploidization problem: smaller changes (inversions, transpositions, gene loss, etc) makes polyploidization difficult to detect

25. Molecular evidence for an ancient duplication of the entire yeast genome Kenneth H. Wolfe & Denis C. Shields Department of Genetics, University of Dublin, Trinity College, Dublin 2, Ireland 100% yeast genome 200% yeast genome 108% yeast genome duplication of the entire S. cerevisiae genome deletion of redundant duplicate copies 2 x 8% in pairs, 92% unique