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.
Giaever
Guri
G
Stanford Genome Technology Center, Stanford University, Palo Alto, California 94304, USA.
Chu
Angela M
AM
Ni
Li
L
Connelly
Carla
C
Riles
Linda
L
Véronneau
Steeve
S
Dow
Sally
S
Lucau-Danila
Ankuta
A
Anderson
Keith
K
André
Bruno
B
Arkin
Adam P
AP
Astromoff
Anna
A
El-Bakkoury
Mohamed
M
Bangham
Rhonda
R
Benito
Rocio
R
Brachat
Sophie
S
Campanaro
Stefano
S
Curtiss
Matt
M
Davis
Karen
K
Deutschbauer
Adam
A
Entian
Karl-Dieter
KD
Flaherty
Patrick
P
Foury
Francoise
F
Garfinkel
David J
DJ
Gerstein
Mark
M
Gotte
Deanna
D
Güldener
Ulrich
U
Hegemann
Johannes H
JH
Hempel
Svenja
S
Herman
Zelek
Z
Jaramillo
Daniel F
DF
Kelly
Diane E
DE
Kelly
Steven L
SL
Kötter
Peter
P
LaBonte
Darlene
D
Lamb
David C
DC
Lan
Ning
N
Liang
Hong
H
Liao
Hong
H
Liu
Lucy
L
Luo
Chuanyun
C
Lussier
Marc
M
Mao
Rong
R
Menard
Patrice
P
Ooi
Siew Loon
SL
Revuelta
Jose L
JL
Roberts
Christopher J
CJ
Rose
Matthias
M
Ross-Macdonald
Petra
P
Scherens
Bart
B
Schimmack
Greg
G
Shafer
Brenda
B
Shoemaker
Daniel D
DD
Sookhai-Mahadeo
Sharon
S
Storms
Reginald K
RK
Strathern
Jeffrey N
JN
Valle
Giorgio
G
Voet
Marleen
M
Volckaert
Guido
G
Wang
Ching-yun
CY
Ward
Teresa R
TR
Wilhelmy
Julie
J
Winzeler
Elizabeth A
EA
Yang
Yonghong
Y
Yen
Grace
G
Youngman
Elaine
E
Yu
Kexin
K
Bussey
Howard
H
Boeke
Jef D
JD
Snyder
Michael
M
Philippsen
Peter
P
Davis
Ronald W
RW
Johnston
Mark
M
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