Comparative genomics identifies a flagellar and basal body proteome that includes the BBS5 human disease gene.
Cilia and flagella are microtubule-based structures nucleated by modified centrioles termed basal bodies. These biochemically complex organelles have more than 250 and 150 polypeptides, respectively. To identify the proteins involved in ciliary and basal body biogenesis and function, we undertook a comparative genomics approach that subtracted the nonflagellated proteome of Arabidopsis from the shared proteome of the ciliated/flagellated organisms Chlamydomonas and human. We identified 688 genes that are present exclusively in organisms with flagella and basal bodies and validated these data through a series of in silico, in vitro, and in vivo studies. We then applied this resource to the study of human ciliation disorders and have identified BBS5, a novel gene for Bardet-Biedl syndrome. We show that this novel protein localizes to basal bodies in mouse and C. elegans, is under the regulatory control of daf-19, and is necessary for the generation of both cilia and flagella.
Li
Jin Billy
JB
Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.
Gerdes
Jantje M
JM
Haycraft
Courtney J
CJ
Fan
Yanli
Y
Teslovich
Tanya M
TM
May-Simera
Helen
H
Li
Haitao
H
Blacque
Oliver E
OE
Li
Linya
L
Leitch
Carmen C
CC
Lewis
Richard Allan
RA
Green
Jane S
JS
Parfrey
Patrick S
PS
Leroux
Michel R
MR
Davidson
William S
WS
Beales
Philip L
PL
Guay-Woodford
Lisa M
LM
Yoder
Bradley K
BK
Stormo
Gary D
GD
Katsanis
Nicholas
N
Dutcher
Susan K
SK
D000818:Animals; D017360:Arabidopsis; D020788:Bardet-Biedl Syndrome / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D002696:Chlamydomonas; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002923:Cilia / Q000235:genetics* / Q000378:metabolism; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D005260:Female; D005407:Flagella / Q000235:genetics* / Q000378:metabolism; D015698:Genomic Library; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D028044:Phosphate-Binding Proteins; D011506:Proteins / Q000235:genetics* / Q000302:isolation & purification; D020543:Proteome / Q000235:genetics*; D034622:RNA Interference; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics
C487434:BBS5 protein, human; D029742:Caenorhabditis elegans Proteins; D003598:Cytoskeletal Proteins; C410596:DAF-19 protein, C elegans; D018076:DNA, Complementary; D028044:Phosphate-Binding Proteins; D011506:Proteins; D020543:Proteome; D014157:Transcription Factors