Primate segmental duplication creates novel promoters for the LRRC37 gene family within the 17q21.31 inversion polymorphism region
- Cemalettin Bekpen1,2,5,
- Ibrahim Tastekin2,
- Priscillia Siswara3,
- Cezmi A. Akdis1 and
- Evan E. Eichler3,4,5
- 1Swiss Institute of Allergy and Asthma Research (SIAF), CH-7270 Davos, Switzerland;
- 2Department of Molecular Biology and Genetics, Bogazici University, Istanbul 34342, Turkey;
- 3Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA;
- 4Howard Hughes Medical Institute, Seattle, Washington 98195, USA
Abstract
The LRRC37 gene family maps to a complex region of the human genome and has been subjected to multiple rounds of segmental duplication. We investigate the expression and regulation of this gene family in multiple tissues and organisms and show a testis-specific expression of this gene family in mouse but a more ubiquitous pattern of expression among primates. Evolutionary and phylogenetic analyses support a model in which new alternative promoters have been acquired during primate evolution. We identify two promoters, Cl8 and particularly Cl3, both of which are highly active in the cerebellum and fetal brain in human and have been duplicated from a promoter region of two unrelated genes, BPTF and DND1, respectively. Two of these more broadly expressed gene family members, LRRC37A1 and A4, define the boundary of a common human inversion polymorphism mapping to chromosome 17q21.31 (the MAPT locus)—a region associated with risk for frontal temporal dementia, Parkinsonism, and intellectual disability. We propose that the regulation of the LRRC37 family occurred in a stepwise manner, acquiring foreign promoters from BPTF and DND1 via segmental duplication. This unusual evolutionary trajectory altered the regulation of the LRRC37 family, leading to increased expression in the fetal brain and cerebellum.
Footnotes
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↵5 Corresponding authors.
E-mail cemalettin.bekpen{at}boun.edu.tr.
E-mail eee{at}gs.washington.edu.
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.134098.111.
- Received October 28, 2011.
- Accepted March 7, 2012.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported License), as described at http://creativecommons.org/licenses/by-nc/3.0/.
