Functional profiling of the Saccharomyces cerevisiae genome.
Determining the effect of gene deletion is a fundamental approach to understanding gene function. Conventional genetic screens exhibit biases, and genes contributing to a phenotype are often missed. We systematically constructed a nearly complete collection of gene-deletion mutants (96% of annotated open reading frames, or ORFs) of the yeast Saccharomyces cerevisiae. DNA sequences dubbed 'molecular bar codes' uniquely identify each strain, enabling their growth to be analysed in parallel and the fitness contribution of each gene to be quantitatively assessed by hybridization to high-density oligonucleotide arrays. We show that previously known and new genes are necessary for optimal growth under six well-studied conditions: high salt, sorbitol, galactose, pH 8, minimal medium and nystatin treatment. Less than 7% of genes that exhibit a significant increase in messenger RNA expression are also required for optimal growth in four of the tested conditions. Our results validate the yeast gene-deletion collection as a valuable resource for functional genomics.
Stanford Genome Technology Center, Stanford University, Palo Alto, California 94304, USA.
Guri
G
Giaever
Angela M
AM
Chu
Li
L
Ni
Carla
C
Connelly
Linda
L
Riles
Steeve
S
Véronneau
Sally
S
Dow
Ankuta
A
Lucau-Danila
Keith
K
Anderson
Bruno
B
André
Adam P
AP
Arkin
Anna
A
Astromoff
Mohamed
M
El-Bakkoury
Rhonda
R
Bangham
Rocio
R
Benito
Sophie
S
Brachat
Stefano
S
Campanaro
Matt
M
Curtiss
Karen
K
Davis
Adam
A
Deutschbauer
Karl-Dieter
KD
Entian
Patrick
P
Flaherty
Francoise
F
Foury
David J
DJ
Garfinkel
Mark
M
Gerstein
Deanna
D
Gotte
Ulrich
U
Güldener
Johannes H
JH
Hegemann
Svenja
S
Hempel
Zelek
Z
Herman
Daniel F
DF
Jaramillo
Diane E
DE
Kelly
Steven L
SL
Kelly
Peter
P
Kötter
Darlene
D
LaBonte
David C
DC
Lamb
Ning
N
Lan
Hong
H
Liang
Hong
H
Liao
Lucy
L
Liu
Chuanyun
C
Luo
Marc
M
Lussier
Rong
R
Mao
Patrice
P
Menard
Siew Loon
SL
Ooi
Jose L
JL
Revuelta
Christopher J
CJ
Roberts
Matthias
M
Rose
Petra
P
Ross-Macdonald
Bart
B
Scherens
Greg
G
Schimmack
Brenda
B
Shafer
Daniel D
DD
Shoemaker
Sharon
S
Sookhai-Mahadeo
Reginald K
RK
Storms
Jeffrey N
JN
Strathern
Giorgio
G
Valle
Marleen
M
Voet
Guido
G
Volckaert
Ching-yun
CY
Wang
Teresa R
TR
Ward
Julie
J
Wilhelmy
Elizabeth A
EA
Winzeler
Yonghong
Y
Yang
Grace
G
Yen
Elaine
E
Youngman
Kexin
K
Yu
Howard
H
Bussey
Jef D
JD
Boeke
Michael
M
Snyder
Peter
P
Philippsen
Ronald W
RW
Davis
Mark
M
Johnston
D048429:Cell Size; D016000:Cluster Analysis; D003470:Culture Media / Q000494:pharmacology; D005690:Galactose / Q000494:pharmacology; D017353:Gene Deletion; D020869:Gene Expression Profiling; D005800:Genes, Fungal; D016681:Genome, Fungal; D006863:Hydrogen-Ion Concentration; D009761:Nystatin / Q000494:pharmacology; D016366:Open Reading Frames / Q000235:genetics; D009994:Osmolar Concentration; D010641:Phenotype; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism*; D012641:Selection, Genetic; D013012:Sorbitol / Q000494:pharmacology
D003470:Culture Media; D020543:Proteome; D029701:Saccharomyces cerevisiae Proteins; D009761:Nystatin; D013012:Sorbitol; D005690:Galactose