Evolutionary Assembled cis-Regulatory Module at a Human Ciliopathy Locus

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. Desp...

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Published inScience (American Association for the Advancement of Science) Vol. 335; no. 6071; pp. 966 - 969
Main Authors Lee, Jeong Ho, Silhavy, Jennifer L., Lee, Ji Eun, Al-Gazali, Lihadh, Thomas, Sophie, Davis, Erica E., Bielas, Stephanie L., Hill, Kiley J., Iannicelli, Miriam, Brancati, Francesco, Gabriel, Stacey B., Russ, Carsten, Logan, Clare V., Sharif, Saghira Malik, Bennett, Christopher P., Abe, Masumi, Hildebrandt, Friedhelm, Diplas, Bill H., Attié-Bitach, Tania, Katsanis, Nicholas, Rajab, Anna, Koul, Roshan, Sztriha, Laszlo, Waters, Elizabeth R., Ferro-Novick, Susan, Woods, C. Geoffrey, Johnson, Colin A., Valente, Enza Maria, Zaki, Maha S., Gleeson, Joseph G.
Format Journal Article
LanguageEnglish
Published American Association for the Advancement of Science 24.02.2012
Subjects
Cilia
Evolution
Evolutionary genetics
Genes
Genetic loci
Genetic mutation
Human genetics
Humans
Intergenic DNA
Phenotypes
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Summary: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.
ISSN:0036-8075
1095-9203