Post on 14-Dec-2015
Réarrangements chromosomiques Evolution des génomes de levuresRéarrangements chromosomiques Evolution des génomes de levures
2ème réunion GTGC Nantes
12 et 13 octobre 2006
Gilles Fischer
Comparative genomics in yeasts:Comparative genomics in yeasts:
significant results:
- Gene identification and annotation
- Sequence comparison and protein evolution
Saccharomyces cerevisiae
Saccharomyces paradoxus
Saccharomyces mikatae
Saccharomyces kudriavzevii
Saccharomyces bayanus
Saccharomyces exiguus
Saccharomyces servazzii
Saccharomyces castellii
Candida glabrata
Zygosaccharomyces rouxii
Kluyveromyces thermotolerans
Kluyveromyces waltii
Saccharomyces kluyveri
Kluyveromyces lactis
Kluyveromyces marxianus
Ashbya gossypii
Pichia angusta
Debaryomyces hansenii
Pichia sorbitophila
Candida guilliermondii
Candida lusitaniae
Candida tropicalis
Candida parapsilosis
Candida albicans
Candida dubliniensis
Yarrowia lipolytica
Schizosaccharomyces pombe
Cryptococcus neoformans
Hem
iasc
om
yce
tes
Archiascomycetes
1
2
3
4
5
6
7
Basidiomycetes
Euascomycetes Neurospora, Magnaporthe, Aspergillus, etc…
Mus musculus
Takifugu rubripesTetraodon negroviridis
Homo sapiens
Ciona intestinalis
100 *
90
70
50
* Data from O. Jaillon et al., Nature, 2004
100
85
65
61
51
48
Comparative genomics in yeasts:Comparative genomics in yeasts:
significant results:
- Gene identification and annotation
- Sequence comparison and protein evolution
- Chromosome rearrangements
1> speciation process
2> level of chromosome reorganisation
3> rates of chromosomal rearrangements
1> speciation process: mechanisms for hybrid sterility1> speciation process: mechanisms for hybrid sterility
- Chromosomal rearrangements
chromosome imbalance at meiosis
-Genetic incompatibilities
Dominant and/or recessive incompatibilitiesChambers et al., 1996 ; Greig et al., 2002
- DNA sequence divergence and Mismatch repair
prevention of recombination between homologsChambers et al., 1996 ; Hunter et al, 1996 ; Greig et al., 2003
Chromosomal evolution in the Saccharomyces sensu stricto complex:
S. cariocanus
S. paradoxus
S. mikatae
S. kudriavzevii
S. cerevisiae
S. bayanusvar. uvarum
Saccharomyces cerevisiae
Saccharomyces paradoxus
Saccharomyces mikatae
Saccharomyces kudriavzevii
Saccharomyces bayanus
Saccharomyces exiguus
Saccharomyces servazzii
Saccharomyces castellii
Candida glabrata
Zygosaccharomyces rouxii
Kluyveromyces thermotolerans
Kluyveromyces waltii
Saccharomyces kluyveri
Kluyveromyces lactis
Kluyveromyces marxianus
Ashbya gossypii
Pichia angusta
Debaryomyces hansenii
Pichia sorbitophila
Candida guilliermondii
Candida lusitaniae
Candida tropicalis
Candida parapsilosis
Candida albicans
Candida dubliniensis
Yarrowia lipolytica
Schizosaccharomyces pombe
Cryptococcus neoformans
Archiascomycetes
1
2
3
4
5
6
7
Basidiomycetes
Euascomycetes Neurospora, Magnaporthe, Aspergillus, etc…
• monophyletic group of species• closely related to S. cerevisiae
• viable hybrids
Electrophoretic Karyotypes:
sensu stricto speciesS. cerevisiae
S1 S2 S3
S4 S5 S6
S1 S2 S6
S4 S5 S3
Chromosomal Translocations: mechanism of post-zygotic isolation?
4 translocations
4 translocations
2 translocations
Chromosomal evolution in Saccharomyces sensu stricto:
94
81
94
99
S. cariocanus
S. paradoxus
S. cerevisiae (as reference)
S. mikatae
S. kudriavzevii
S. bayanus
(0 translocation)
(0 translocation)
ITS1
Fischer et al., Nature 2000
QuickTime™ et undécompresseur TIFF (non compressé)
sont requis pour visionner cette image. 0.2 to 0.5 X of genome coverage
In 2000: Genolevures I, Genomic exploration of 13 yeast species
3 - 5 kb random genomic fragments cloned in sequencing plasmid
Left sequence tag
Gene 1
Right sequence tag
Gene 2
Souciet et al., FEBS Letters (special issue), 2000
S.bayanus gene 1 gene 2
0.4X about 2000 neighboring gene couples :
=> 35 synteny breakpoints (80 predicted in total)
3 corresponded to translocations
= > 32 breakpoints left ???
Saccharomyces cerevisiae
Saccharomyces paradoxus
Saccharomyces mikatae
Saccharomyces kudriavzevii
Saccharomyces bayanus
Saccharomyces exiguus
Saccharomyces servazzii
Saccharomyces castellii
Candida glabrata
Zygosaccharomyces rouxii
Kluyveromyces thermotolerans
Kluyveromyces waltii
Saccharomyces kluyveri
Kluyveromyces lactis
Kluyveromyces marxianus
Ashbya gossypii
Pichia angusta
Debaryomyces hansenii
Pichia sorbitophila
Candida guilliermondii
Candida lusitaniae
Candida tropicalis
Candida parapsilosis
Candida albicans
Candida dubliniensis
Yarrowia lipolytica
Schizosaccharomyces pombe
Cryptococcus neoformans
Hem
iasc
om
yce
tes
Archiascomycetes
1
2
3
4
5
6
7
Basidiomycetes
Euascomycetes Neurospora, Magnaporthe, Aspergillus, etc…
S.cerevisiae gene 1’ gene 2’
Synteny conservation
S.cerevisiae gene 1’
gene 2’
Synteny breakpoint
X
YJR
052w
YJR
053w
YJR
054w
YJR
055w
YJR
057w
YJR056c
YJR058c
YML051w
K. thermotolerans :
YJR
052w
YM
L046w
YJR
055w
YM
L051w
YM
L049w
K. lactis :
YJR
052w
YM
L046w
YJR
053w
YM
L048w
YJR
052w
YJR
053w
YJR
054w
YJR
055w
YJR
057w
YJR056c
YJR058c
YML051w
YML046w
YML048w
YML049w
(i) Gene transposition:
YJR
052w
YJR
053w
YJR
054w
YJR
055w
YJR
057w
YJR056c
YJR058c
YML051w
YML046w
YML048w
YML049w
DUPLICATION
YJR
052w
YJR
053w
YJR
054w
YJR
055w
YJR
057w
YJR056c
YJR058c
YML051w
YML046w
YML048w
YML049w
(i) Gene transposition:
YJR
052w
YJR
053w
YJR
054w
YJR
055w
YJR
057w
YJR056c
YJR058c
YML051w
YML046w
YML048w
YML049w
YJR
052w
YJR
053w
YJR
054w
YJR
055w
YJR
057w
YJR056c
YJR058c
YML051w
YML046w
YML048w
YML049w
RECIPROCAL GENE LOSS
(i) Gene transposition:
YM
L051w
YML046w
YML048w
YML049w
(i) Gene transposition:
YJR
052w
YJR
053w
YJR
054w
YJR
055w
YJR
057w
YJR056c
YJR058c
YM
L047c
X
XIII
S. cerevisiae
YML046w
YML048w
YML049w
(i) Gene transposition:
YJR
052w
YJR
053w
YJR
054w
YJR
055w
YJR
057w
YJR056c
YJR058c
YM
L047c
X
XIII
S. bayanus
YML051w
Fischer et al., Genome Research 2001
IVtII
SuYBR60c SuYBR061c
SuYDR037w
IItIVSuYDR038c
SuYDR037w
S. uvarum
YBR60c
II
YBR061c
YDR036cIV
YDR038c
YDR037w(KRS1)
S. cerevisiaeRelic of
YDR037w paralog
1000 2000 3000 4000 5000
YBR060c YBR061c
YD
R0
37w
(KR
S1)
Stringency 15/23
(ii) Species specific gene duplication:
Fischer et al., Genome Research 2001
Reciprocal gene loss => SPECIATION by a version of the Bateson-Dobzhansky-Muller mechanism:
duplication
Duplicate gene loss
Reciprocal gene loss
Hybrid 2n
meiosis
1/4 of dead spores
Reciprocal gene loss => SPECIATION by a version of the Bateson-Dobzhansky-Muller mechanism:
Scannell et al., Nature 2006
Sequence divergence and meiotic sterility: sequencing of 6 genes in 41 strains
Liti et al., Genetics in press
S. cariocanus
0,3%
0,15%
0,1%
0,6%
1%
5%
15%
Sequence divergence and meiotic sterility: sequencing of 6 genes in 41 strains
Liti et al., Genetics in press
spore viability: - 1 reciprocal translocation=> 50% - 1 non reciprocal translocation => 75% - 4 reciprocal translocations => 6%
Sequence divergence and meiotic sterility: sequencing of 6 genes in 41 strains
Liti et al., Genetics in press
Conclusions: speciation results from several mechanisms superimposed?
S. cerevisiae
C. glabrata
K. lactis
S. paradoxus
S. cariocanus
S. bayanus
S. castellii
K. waltii
A. gossypii
Increasing DNA divergence
WholeGenome Duplication
Reciprocal gene loss
Chromosomal translocations
2> Level of chromosome reorganisation: Genolevures 2 Dujon et al., Nature, 2004
2> Level of chromosome reorganisation: Genolevures 2 Dujon et al., Nature, 2004
Human pathogen
Model organism
Cryotolerant, halotolerant marine yeast
Alkane-using yeast
S. cerevisiae
C. glabrata
K. lactis
D. hansenii
Y. lipolytica
ADHoRe sofware ( Vandepoele et al., Genome Res, 2002)
gene 1 gene 2gene 3gene 4gene 5gene 6gene 7gene 8gene 9gene 10gene 11gene 12gene 13gene 14gene 15gene 16
gene a gene b gene c gene d gene e gene f gene g gene h gene i gene j
Genome 1
Genome
2
gap
r2
Synteny blocks
10 pairwise comparisons
Duplication blocks5 intra comparisons
S. cerevisiae C. glabrata
Blocks of ancestral duplications
S. cerevisiae C. glabrata
Total nb of duplicated blocksinternal to chromosomes 56 20sutelomeric 21 0
Block size (kb) mean 42 27max. 243 89
Nb of gene pairs /block mean 5.8 3.8max. 15 6
Dujon et al., Nature 2004
1
2
3
4
S. cerevisiae
C. glabrata
K. lactis
D. hansenii
Y. lipolytica
WholeGenome Duplication
More extensive loss of duplicated genes and reductive evolution
Extensive loss of duplicated genes
Oth
er m
echa
nism
s of
dup
licat
ion
Overall genome redundancy
(nb of genes in families over total nb of genes)
44.2 %
35.1 %
31.8 %
51.5 %
41.8 %
GENOME DUPLICATION AND GENOME REDUNDANCYGENOME DUPLICATION AND GENOME REDUNDANCY
K. lactis D. hansenii Y. lipolytica
Total nb of duplicated blocksinternal to chromosomes 8 5 2sutelomeric 1 10 0
Block size (kb) mean 9 19 90max. 25 59 148
Nb of gene pairs /block mean 4.3 3.7 4.0max. 11 6 4
K. lactis D. hansenii Y. lipolytica
Sporadic segmental duplications
?
Blocks of ancestral duplications
Example of a tandem repeat array in D. hanseniiExample of a tandem repeat array in D. hansenii
D. hansenii_ CONTIG=DEHAOK
Similar to S. cerevisiae YHR179w OYE2 NADPH dehydrogenase (old yellow enzyme), isoform 1
pseudogenes pseudogenes
Amino-acid sequence identity between copies: from 82 % to 95 %
total nb of direct total nb of
tandem pairs orientation arrays
S. cerevisiae 61 79% 50
C. glabrata 47 83% 32
K. lactis 36 72 % 33
D. hansenii 329 92 % 247
Y. lipolytica 54 72 % 48
1
2
3
4
S. cerevisiae
C. glabrata
K. lactis
D. hansenii
Y. lipolytica
WholeGenome Duplication
More extensive loss of duplicated genes and reductive evolution
Extensive loss of duplicated genes
GENOME DUPLICATION AND GENOME REDUNDANCYGENOME DUPLICATION AND GENOME REDUNDANCY
Tandem repeat formation
Segmental duplication
Segmental duplication
Segmental duplication
WGDsegmental duplicationsgene tandem duplications
LOSS -> sequence degeneration deletion
New functionsGene dosageGene order changes and translocations
Pseudogenes and gene relicsSpeciation
<- DUPLICATION
S. cerevisiae
C. glabrata
K. lactis
S. paradoxus
S. cariocanus
S. bayanus
D. hansenii
Y. lipolytica
Low genome reorganization:
10 translocations in total
=> High synteny conservation
Synteny conservation among Hemiascomycetes:Synteny conservation among Hemiascomycetes:
0.1
1000
1000
1000
1000
1000
1000
S. paradoxus
S. mikatae
S. bayanus
S. cerevisiae
C. glabrata
K. lactis
D. hansenii
Y. lipolytica
Low genomereorganization
massivereorganization
4 translocations
2 translocations
4 translocations
reference
0
0
S. paradoxus
S. kudriavzevii
S. cariocanus
S. mikatae
S. bayanus
S. cerevisiae 0
Variable rates of rearrangements?
0.1
923
987
1000
1000
1000
1000
1000
1000
1000
S. paradoxus
S. mikatae
S. bayanus
C. albicans
K. waltii
S. cerevisiae
C. glabrata
A. gossypii
K. lactis
D. hansenii
Y. lipolytica
Gene order conservation: GOC
=5
=5Species 1 gene 1 gene 2
Species 2 gene 1’ gene X
?
Rates of genome rearrangements among Hemiascomycetes:Rates of genome rearrangements among Hemiascomycetes:
K. waltii
A. gossypi
K. lactis
D. hansenii
Y. lipolytica
S. cerevisiae
S. paradoxus
S. mikatae
S. bayanus
C. glabrata
C. albicans
1
9
8
5
4
2
3
6
7
i
GOC
0.88
GOL
0.12
GOLest
X12+X13+X15+X17+X19
X1
X2X4
X3
X5
X7
X8X9
X10
X11
X12
X13
X15
X16
X17X18
X19
X14
X6
Rates of genome rearrangements among Hemiascomycetes:Rates of genome rearrangements among Hemiascomycetes:
Fischer et al., PLoS Genetics, 2006
1
1.20
1.891.43
0.98
9
8
5
1.63
0.23
4.090.75
0.43
2.18
1.13
0.81
1.00
0.29
0.080.54
0.51
4
2
3
6
7
< 10-2
< 10-2
WGD
K. waltii
A. gossyp
K. lactis
D. hansenii
Y. lipolytica
S. cerevisiae
S. paradoxus
S. mikatae
S. bayanus
C. glabrat
C. albicans
GOC
0.88
GOL
0.12
GOLest
X12+X13+X15+X17+X19
Rates of genome rearrangements among Hemiascomycetes:Rates of genome rearrangements among Hemiascomycetes:
Rates of genome rearrangements among Hemiascomycetes:Rates of genome rearrangements among Hemiascomycetes:
Fischer et al., PLoS Genetics, 2006
1
1.20
1.891.43
0.98
9
8
5
1.63
0.23
4.090.75
0.43
2.18
1.13
0.81
1.00
0.29
0.080.54
0.51
4
2
3
6
7
< 10-2
< 10-2
WGD
K. waltii
A. gossyp
K. lactis
D. hansenii
Y. lipolytica
S. cerevisiae
S. paradoxus
S. mikatae
S. bayanus
C. glabrat
C. albican
0.5
0.6
0.7
0.8
1
C. albicans
C. glabrataD. hansenii
S. cerevisiaeS. mikataeS. paradoxus
K. lactis
Y. lipolytica
S. bayanus
K. waltii
A. gossypii
0.9
Genome instability scale:
Synteny conservation among Hemiascomycetes: Genome reorganization
5 10 15 20 25 30 35 40 45 50 >50
number of genes in synteny blocks
0
50
100
150
200
250
300
Nu
mber
of
synte
ny b
lock
s
S. cerevisiae vs C. glabrata
K. lactis vs A. gossypii
Synteny conservation among Hemiascomycetes: Constraints onto gene order changes
0 0.1 0.2 0.3 0.4 0.5 0.6
Sc + Kl
Sc + Dh
Sc + Yl
Sc
Sc + Cg
Sc + Cg + Kl
Sc + Cg + Kl + Dh
Sc + Cg + Kl + Dh + Yl
(10/23)
(40/113)
(625/2481)
(58/157)
(101/340)
(886/3814)
(914/4268)
(1176/5807)
Proportion of genes in synteny that are essentials
• Moderate genome reorganization between closely related species Few translocations90% of the synteny breakpoints are due to alternative loss of duplicated genes
• Major role of duplications onto chromosomal dynamics WGD Segmental duplications tandem gene duplications
•Massive genome reorganization at larger evolutionary distances: hundreds of interchromosomal rearrangements Important reshuffling of gene order
•Variable rates of genome rearrangements between lineages but also at different times within a lineage:
pathogenic yeasts having the most unstable genomes
Conclusions :
- Unité de Génétique Moléculaire des Levures
Romain Koszul, Celia Payen, Ingrid Lafontaine, Bernard Dujon
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- The GénolevuresGénolevures Sequencing Consortium GDR 2354 CNRS
Plateforme séquençage, Genopole Institut PasteurGenoscope
Cécile NeuvéglisePascal DurrensJean-Luc Souciet
- Unité de Genetique des Génomes Bactériens
Eduardo Rocha
- Unité Génomique des Microorganismes Pathogènes
Massimo Vergassola
- Laboratoire de Biologie Moléculaire de la Cellule (ENS Lyon)
Frédéric Brunet
- Genome Stability Group (Nottinhgam, UK)
Edward J. Louis
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