Evolutionarily assembled cis-regulatory module at a human ciliopathy locus.


Journal Article

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.

Full Text

Cited Authors

  • Lee, JH; Silhavy, JL; Lee, JE; Al-Gazali, L; Thomas, S; Davis, EE; Bielas, SL; Hill, KJ; Iannicelli, M; Brancati, F; Gabriel, SB; Russ, C; Logan, CV; Sharif, SM; Bennett, CP; Abe, M; Hildebrandt, F; Diplas, BH; Attié-Bitach, T; Katsanis, N; Rajab, A; Koul, R; Sztriha, L; Waters, ER; Ferro-Novick, S; Woods, CG; Johnson, CA; Valente, EM; Zaki, MS; Gleeson, JG

Published Date

  • February 24, 2012

Published In

Volume / Issue

  • 335 / 6071

Start / End Page

  • 966 - 969

PubMed ID

  • 22282472

Pubmed Central ID

  • 22282472

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.1213506


  • eng

Conference Location

  • United States