ZFIN ID: ZDB-PUB-200522-20
Evolutionarily assembled cis-regulatory module at a human ciliopathy locus
Lee, J.H., Silhavy, J.L., Lee, J.E., Al-Gazali, L., Thomas, S., Davis, E.E., Bielas, S.L., Hill, K.J., Iannicelli, M., Brancati, F., Gabriel, S.B., Russ, C., Logan, C.V., Sharif, S.M., Bennett, C.P., Abe, M., Hildebrandt, F., Diplas, B.H., AttiƩ-Bitach, T., Katsanis, N., Rajab, A., Koul, R., Sztriha, L., Waters, E.R., Ferro-Novick, S., Woods, C.G., Johnson, C.A., Valente, E.M., Zaki, M.S., Gleeson, J.G.
Date: 2012
Source: Science (New York, N.Y.)   335: 966-9 (Journal)
Registered Authors: Davis, Erica, Hildebrandt, Friedhelm, Katsanis, Nicholas, Lee, Ji Eun
Keywords: none
MeSH Terms:
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cerebellar Diseases/genetics*
  • Cerebellar Diseases/metabolism
  • Cerebellar Diseases/pathology
  • Cilia/metabolism
  • Cilia/ultrastructure*
  • Conserved Sequence
  • DNA, Intergenic
  • Evolution, Molecular*
  • Eye Abnormalities/genetics*
  • Eye Abnormalities/metabolism
  • Eye Abnormalities/pathology
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Genetic Heterogeneity
  • Genetic Loci*
  • Humans
  • Kidney Diseases, Cystic/genetics*
  • Kidney Diseases, Cystic/metabolism
  • Kidney Diseases, Cystic/pathology
  • Membrane Proteins/chemistry
  • Membrane Proteins/genetics*
  • Membrane Proteins/metabolism
  • Molecular Sequence Data
  • Multigene Family
  • Mutation
  • Mutation, Missense
  • Phenotype
  • Protein Transport
  • Regulatory Sequences, Nucleic Acid*
  • Retina/abnormalities
  • Retina/metabolism
  • Retina/pathology
  • Transport Vesicles/metabolism
  • Transport Vesicles/ultrastructure
PubMed: 22282472 Full text @ Science
Neighboring genes are often coordinately expressed within cis-regulatory modules, but evidence that nonparalogous genes share functions in mammals is lacking. Here, we report that mutation of either TMEM138 or TMEM216 causes a phenotypically indistinguishable human ciliopathy, Joubert syndrome. Despite a lack of sequence homology, the genes are aligned in a head-to-tail configuration and joined by chromosomal rearrangement at the amphibian-to-reptile evolutionary transition. Expression of the two genes is mediated by a conserved regulatory element in the noncoding intergenic region. Coordinated expression is important for their interdependent cellular role in vesicular transport to primary cilia. Hence, during vertebrate evolution of genes involved in ciliogenesis, nonparalogous genes were arranged to a functional gene cluster with shared regulatory elements.