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Administrative coordination of systematic sequencing of the yeast genome - II


General administration and coordination of the project:
-Subcontracts to DNA coordinators (Chromosomes IV, VII, XII, XV, XVI, telomeres) and to 74 sequencing laboratories.
-Initial advance payments to each subcontractor.
-Detailed accountancy of the base pairs produced by each sequencing laboratory.
-Subsequent payments on the basis of 2 ECU per final base pair sequenced as approved by the DNA and informatic coordinators.
-Subsequent payments to DNA coordinators according to progress.
-Continuous interaction with each DNA coordinator, informatic coordinator and sequencing laboratory.
-Organisation of contractor meetings.
Preparation of organised libraries from chromosome IV and XII (Hoheisel).
Construction of telomeric clones from all the yeast chromosomes
Completion of the sequencing of chromosomes VII (1091 kb) and XV (1091 kb) and partial sequencing of chromosomes IV (598 kb), XII (472 kb) and XVI (283 kb).
-Construction of libraries of overlapping clones to cover the portion of yeast chromosomes to be sequenced as unique contigs.
-Sorting of clones and construction of high resolution (`sequence-ready') physical maps.
-Distribution of clones to participants for sequencing of the entire chromosomes.
-Implementation of `quality controls' for the sequences determined by the participants.
-Assembly of the complete sequence of chromosomes VII and XV, and of the partial sequence of chromosomes IV, XII and XVI from the sets of overlapping clones and interpretation of the sequence.
Organisation of contractor meetings in Lisbon, P (1995) and Trieste, I (1996).
Informatic coordination (assembly and analysis) of chromosome IV, XII and XVI.
Since 24th April 1996 the full sequence of the yeast genome has been available with the release of the final portion of the sequence into databases accessible by the entire research community. This data will subsequently be published in the scientific literature.
The yeast genome is the first genome from a higher species to be completely sequenced. This truly international achievement is largely the result of this European Commission project initiated seven years ago (BAP - BRIDGE - BIOTECH I & II programmes) and which has involved almost 100 European laboratories working in a highly coordinated manner together with laboratories from the US, Canada and Japan.
Three years ago, our consortium of 35 European laboratories (BAP programme) published the first complete sequence (315 356 bp) of an eukaryotic chromosome, that of chromosome III of S. cerevisiae (Oliver et al. Nature 357, 38-56, 1993). Its publication in Nature, as well as featuring a record number of scientists (147), had an enormous impact. Indeed it was recently identified by Nature as one of the most significant scientific articles of all time.
During years 91-93, our consortium (32 laboratories in the BRIDGE programme) turned its efforts to the sequencing of the 666 448 bp of yeast chromosome XI (Dujon et al. Nature 369, 371-378, 1992) and to the sequencing of the 807 188 bp of chromosome II (Feldmann et al., EMBO journal 13, 5795-5809, 1994).
And finally, our EU network (56 laboratories in the BIOTECH I programme and 74 in the BIOTECH II programme) has completed its part of the sequencing of the yeast genome (55% of the total) with chromosomes IV, VII, X, XII, XIV, XV and XVI.

The sequence data has already provided a wealth of information, allowing considerable advances in the understanding of the basic mechanisms of life in higher cells. This, in turn, is useful not only to companies using yeast in food processes or for the production of industrial enzymes and therapeutical agents, but also for research into human health.
More than 50% of the yeast genes have turned out to be quite similar to human genes. Thus, a yeast cell has much in common with a human cell. The availability of these fully sequenced genes in yeast provides new leads for research into human health disorders such as colon cancer, cystic fibrosis, etc.

At the genome level:
- Compactness: one gene per 2 Kb
- Redundancy: over 30%
- Synteny with industrial and pathological yeasts

At the chromosome level:
- GC waves
- Telomere structures
- Ty and tRNAs
- Cen and Ars
- Recombination hot spots

At the protein level:
- Complete inventory of all 6000 cell proteins
- Over 2000 ORPHAN genes
- Human disease homologues

At the manipulated cell level:
- Production by yeast of plant and human proteins
- Use of yeast for drug screening


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