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

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

image taken from

Wolfe 2001

Phylogenetic positions of

some likely polyploidy

events during eukaryote

evolution

Chytridiomycota (e.g., water molds)

Zygomycota(e.g., bread molds)

Basidiomycota(e.g., mushrooms)

Ascomycota(e.g., yeasts)

FungiArchaeascomycetes(e.g., fission yeas: Schizocaccharomyces pombe)

Hemiascomycetes: budding yeasts(e.g., Saccharomyces cerevisiae, Candida albicans, Pichia pastoris)

Euascomycetes: filamentous ascomycetes(Aspergillus, Neurospora, Penicillium)

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.

Molecular evidence for an ancient duplication of the entire yeast genomeKenneth H. Wolfe & Denis C. ShieldsDepartment of Genetics, University of Dublin, Trinity College, Dublin 2, Ireland

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%

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%

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 108 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 108 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?

Main conclusions:1. there was one single duplication event2. the duplication happened before Saccharomyces and Kluyveromyces diverged

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 studiesGenomic Exploration of the Hemiascomycetous Yeasts: 2. Data generation and processingGenomic Exploration of the Hemiascomycetous Yeasts: 3. Methods and strategies used for sequence analysis and

annotationGenomic Exploration of the Hemiascomycetous Yeasts: 4. The genome of Saccharomyces cerevisiae revisitedGenomic Exploration of the Hemiascomycetous Yeasts: 5. Saccharomyces bayanus var. uvarumGenomic Exploration of the Hemiascomycetous Yeasts: 6. Saccharomyces exiguusGenomic Exploration of the Hemiascomycetous Yeasts: 7. Saccharomyces servazziiGenomic Exploration of the Hemiascomycetous Yeasts: 8. Zygosaccharomyces rouxiiGenomic Exploration of the Hemiascomycetous Yeasts: 9. Saccharomyces kluyveriGenomic Exploration of the Hemiascomycetous Yeasts: 10. Kluyveromyces thermotoleransGenomic Exploration of the Hemiascomycetous Yeasts: 11. Kluyveromyces lactisGenomic Exploration of the Hemiascomycetous Yeasts: 12. Kluyveromyces marxianus var. marxianusGenomic Exploration of the Hemiascomycetous Yeasts: 13. Pichia angustaGenomic Exploration of the Hemiascomycetous Yeasts: 14. Debaryomyces hansenii var. hanseniiGenomic Exploration of the Hemiascomycetous Yeasts: 15. Pichia sorbitophilaGenomic Exploration of the Hemiascomycetous Yeasts: 16. Candida tropicalisGenomic Exploration of the Hemiascomycetous Yeasts: 17. Yarrowia lipolyticaGenomic Exploration of the Hemiascomycetous Yeasts: 18. Comparative analysis of chromosome maps and synteny

with Saccharomyces cerevisiaeGenomic Exploration of the Hemiascomycetous Yeasts: 19. Ascomycetes-specific genesGenomic Exploration of the Hemiascomycetous Yeasts: 20. Evolution of gene redundancy compared to

Saccharomyces cerevisiaeGenomic Exploration of the Hemiascomycetous Yeasts: 21. Comparative functional classification of genes

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

• 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

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)

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”

ScienceExpress: March 4, 2004

Nature: March 7, 2004

taken from J Zhang, TREE 2003

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

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

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

Chytridiomycota (e.g., water molds)

Zygomycota(e.g., bread molds)

Basidiomycota(e.g., mushrooms)

Ascomycota(e.g., yeasts)

FungiArchaeascomycetes(e.g., fission yeas: Schizocaccharomyces pombe)

Hemiascomycetes: budding yeasts(e.g., Saccharomyces cerevisiae, Candida albicans, Pichia pastoris)

Euascomycetes: filamentous ascomycetes(Aspergillus, Neurospora, Penicillium)

Molecular evidence for an ancient duplication of the entire yeast genomeKenneth H. Wolfe & Denis C. ShieldsDepartment 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