Comparative Genomics Identifies a Flagellar and Basal Body Proteome That Includes the BBS5 Human Disease Gene

Cell. 2004 May 14;117(4):541-52. doi: 10.1016/s0092-8674(04)00450-7.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arabidopsis
  • Bardet-Biedl Syndrome / genetics*
  • Bardet-Biedl Syndrome / metabolism
  • Bardet-Biedl Syndrome / physiopathology
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / genetics
  • Chlamydomonas
  • Chromosomes, Human, Pair 2 / genetics
  • Cilia / genetics*
  • Cilia / metabolism
  • Cytoskeletal Proteins
  • DNA Mutational Analysis
  • DNA, Complementary / analysis
  • DNA, Complementary / genetics
  • Female
  • Flagella / genetics*
  • Flagella / metabolism
  • Genomic Library
  • Humans
  • Male
  • Mice
  • Molecular Sequence Data
  • Mutation / genetics
  • Pedigree
  • Phosphate-Binding Proteins
  • Proteins / genetics*
  • Proteins / isolation & purification
  • Proteome / genetics*
  • RNA Interference
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid
  • Transcription Factors / genetics

Substances

  • BBS5 protein, human
  • Caenorhabditis elegans Proteins
  • Cytoskeletal Proteins
  • DAF-19 protein, C elegans
  • DNA, Complementary
  • Phosphate-Binding Proteins
  • Proteins
  • Proteome
  • Transcription Factors