Transcript Pi kur, 2004

Yeast genome sequencing: the
power of comparative genomics
Molecular Microbiology (2004)53(2), 381–389
MEDG 505, 03/02/04, Han Hao
Outline
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Introduction
Phylogenetic relationship
Speciation
Gene and regulatory motifs
Evolution
Conclusion
Discussion
Introduction
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Over a dozen yeast genomes have been sequenced.
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Closely related yeasts genomes will provide
information on:
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Coding potential and regulatory sequences
Genes specific for a certain species
Development of a methodological approach to study
phylogenetic relationship
Mechanism involved in the generation of new species
Deduce yeast evolutionary history
Deduce important motifs (for example in gene expression)
Useful for industry application and fighting yeast pathogens
Newly sequenced yeasts will be new model
organisms
Phylogenetic relationship
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One of the most pervasive challenges in
molecular phylogenetics is the
incongruence between phylogenies
obtained using different data sets, such
as individual genes.
Phylogenetic relationship
Trees generated from single-gene data sets frequently generate incongruences
Rokas et al. 2003, Nature
Phylogenetic relationship
Combined analysis of multiple genes will have better solution plus
congruences
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Phylogenetic tree derived from
analysis of a dataset comprised
of nucleotide sequences from
18S, 5.8S/alignable ITS, and
26S (three regions) rDNAs, EF1 , mitochondrial small-subunit
rDNA and COX II.
Kurtzman and Robnett, 2003
Phylogenetic relationship
Phylogenetic relationship
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Q: What is the minimal amount of gene that
could be sufficient to recover a valid species
tree?
A: For yeast, a minimum of 20 genes is
required to recover 95% bootstrap values for
each branch of the species tree (Rokas et al.
2003, Nature)
Phylogenetic relationship
Phylogenetic tree
based on18s rRNA
Rokas et al. 2003, Nature
Phylogenetic relationship
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Use of genome-wide data sets may provide
unprecedented power not only in testing
specific phylogenetic hypotheses but also in
precise reconstruction of the historical
associations of all the taxa analysed.
In other cases the amount of sequence
information needed to resolve specific
relationships will be dependent on the
particular phylogenetic history under
examination.
Speciation
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Species: a group of organisms defined by
their inability to mate successfully and
produce viable offspring with other species.
(species barrier)
What cause speciation?
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Chromosome numbers and sizes changed
Chromosomal translocation
Gene order remodelled
Gene loss/gain
Horizon transfer
Speciation
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The principal problem in studying the
molecular mechanisms of speciation is
the difficulty in separating the effects of
karyotypic rearrangements from
genome-wide genetic incompatibilities.
Speciation
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Facts:
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Rearrangements within the nuclear
genome have been common during yeast
evolution.
Saccharomyces sensu stricto yeasts can
mate with each other but interspecific
pairings result predominantly in sterile
hybrids.
Speciation
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Chromosomal translocations in yeast might contribute
to the reproductive isolation among sensu stricto
species, but are not the only cause of speciation.
(Deineri et al. 2003, Nature)
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A method for generating precisely located chromosomal
translocations.
If the chromosome were rearranged, the species barrier
almost disappeared.
New genome sequences will increase the
opportunities for further experiments on chromosome
stability and species barriers.
Gene and regulatory motifs
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Large-scale comparisons of genomes
address basic genomics questions
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Number of functional genes
Identification of species-specific genes
Distribution of genes among functional
families
Gene density, gene order et al
Gene and regulatory motifs
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Multi-steps
process of
comparative
sequence
analysis
Frazer et al. 2003, Genome Research
Gene and regulatory motifs
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Based on comparative genomics:
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The number of genes for S. cerevisiae
predicted to be around 5800 ( Much less
than previous prediction >6000)
Discovery of novel genes, novel introns et
al.
Discovery of ncRNA genes.
Identification of regulatory sequences.
Gene and regulatory motifs
Cliften et. al. 2003, Science, Finding Functional Features in Saccharomyces Genomes by Phylogenetic Footprinting
Gene and regulatory motifs
Cliften et. al. 2003, Science, Finding Functional Features in Saccharomyces Genomes by Phylogenetic Footprinting
Gene and regulatory motifs
Cliften et. al. 2003, Science, Finding Functional Features in Saccharomyces Genomes by Phylogenetic Footprinting
Gene and regulatory motifs
Cliften et. al. 2003, Science, Finding Functional Features in Saccharomyces Genomes by Phylogenetic Footprinting
Gene and regulatory motifs
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The genomes of higher eukaryotes
consist a lot of non-functional
sequences that are difficult to align and
the regulatory motifs might locate far
away from the genes they control.
Evolution
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Facts: There are two kinds of yeasts, aerobic and
anaerobi yeasts.
Facts: Sexually reproducing yeasts can undergo
mating between either heterothallic lines or
homothallic line. In S. cerevisiae, homothallism can
be switched to heterothallism. (The present of HO
gene is required for homothallism.)
Q: when and how did the progenitor of
Saccharomyces yeasts develop these basic characters
and what were the molecular mechanisms operating
during this yeast’s evolutionary history?
Evolution
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Two molecular mechanisms, wholegenome duplication and horizontal gene
transfer, are proposed to play a major
role in the evolutionary history of the
Saccharomyces complex yeasts.
Evolution
The whole-genome duplication
and horizontal transfer of genetic
material provided new genes,
which became the background
for the development of
facultative anaerobic lifestyle,
homothallism and efficient
glucose repression circuit.
The origin of several modern yeast traits.
Comparative genomics now
helps to place these events at
different branching points of the
yeast phylogenetic tree and
estimates the relative timing of
these events
Conclusion
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Comparative genomics study of yeast
genomes
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Phylogenetic relationship
Speciation
Genes and regulatory motifs
Evolution
Discussion
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How to organize the yeast genome sequences into a single
database? (Ensembl/UCSC like Genome browser)?
Resources
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Saccharomyces Genome Database:
http://www.yeastgenome.org/
SCPD: The Promoter Database of
Saccharomyces cerevisiae:
http://cgsigma.cshl.org/jian/
MIPS Saccharomyces cerevisiae group:
http://mips.gsf.de/genre/proj/yeast/
Saccharomyces Genome Sequencing at the
GSC: (Cliften et.al 2003, Science)
http://www.genome.wustl.edu/projects/yeast
References
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Cliften, P., et al. (2003) Finding functional features
inSaccharomyces genomes by phylogenetic footprinting. Science
301: 71–76.
Delneri, D., et al. (2003) Engineering evolution to study
speciation in yeasts. Nature 422: 68–72.
Frazer, K.A., et al. (2003) Cross-species sequence comparisons:
a review of methods and available resources.Genome Res 13:
1–12.
Kellis, M., et al. (2003) Sequencing and comparison of yeast
species to identify genes and regulatory elements. Nature 423:
241–254.
Rokas, A., et al. (2003) Genome-scale approaches to resolving
incongruence in molecular phylogenies. Nature 425: 798–804.
Thank you!