The first three authors are co-first authors.
Theria-Specific Homeodomain and cis-Regulatory Element Evolution of the Dlx3–4 Bigene Cluster in 12 Different Mammalian Species†
Article first published online: 5 SEP 2012
Copyright © 2012 Wiley Periodicals, Inc.
Journal of Experimental Zoology Part B: Molecular and Developmental Evolution
Volume 318, Issue 8, pages 639–650, December 2012
How to Cite
2012. Theria-specific homeodomain and cis-regulatory element evolution of the Dlx3–4 bigene cluster in 12 different mammalian species. J. Exp. Zool. (Mol. Dev. Evol.)318B:639–650., , , , , , , , .
Data deposition: The sequence data from this study have been submitted to GenBank under accession nos. AC136964, AC136965, AC136966, AC136967, AC136968, AC144399, AC144400, AC144401, AC144402, AC149030, AC149031, AC156624.
- Issue published online: 30 NOV 2012
- Article first published online: 5 SEP 2012
- Manuscript Accepted: 10 JUL 2012
- Manuscript Revised: 6 JUL 2012
- Manuscript Received: 15 MAY 2012
- United States Department of Energy. Grant Numbers: DE-FG03-01ER63273, DE-FG03-01ER63272, DE-F602-01ER63274
- JSPS Grant-in-Aid for Scientific Research. Grant Number: 22570218
- MEXT Grant-in-Aid for Scientific Research on Innovative Areas. Grant Number: 24113520
- National Human Genome Research Institute. Grant Number: HG02526
The mammalian Dlx3 and Dlx4 genes are configured as a bigene cluster, and their respective expression patterns are controlled temporally and spatially by cis-elements that largely reside within the intergenic region of the cluster. Previous work revealed that there are conspicuously conserved elements within the intergenic region of the Dlx3–4 bigene clusters of mouse and human. In this paper we have extended these analyses to include 12 additional mammalian taxa (including a marsupial and a monotreme) in order to better define the nature and molecular evolutionary trends of the coding and non-coding functional elements among morphologically divergent mammals. Dlx3–4 regions were fully sequenced from 12 divergent taxa of interest. We identified three theria-specific amino acid replacements in homeodomain of Dlx4 gene that functions in placenta. Sequence analyses of constrained nucleotide sites in the intergenic non-coding region showed that many of the intergenic conserved elements are highly conserved and have evolved slowly within the mammals. In contrast, a branchial arch/craniofacial enhancer I37-2 exhibited accelerated evolution at the branch between the monotreme and therian common ancestor despite being highly conserved among therian species. Functional analysis of I37-2 in transgenic mice has shown that the equivalent region of the platypus fails to drive transcriptional activity in branchial arches. These observations, taken together with our molecular evolutionary data, suggest that theria-specific episodic changes in the I37-2 element may have contributed to craniofacial innovation at the base of the mammalian lineage. J. Exp. Zool. (Mol. Dev. Evol.) 9999B:639–650, 2012. © 2012 Wiley Periodicals, Inc.