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Open Access Research article

Ultraconserved coding regions outside the homeobox of mammalian Hox genes

Zhenguo Lin12*, Hong Ma12 and Masatoshi Nei12

Author Affiliations

1 Department of Biology and Institute of Molecular Evolutionary Genetics, Pennsylvania State University, University Park, PA 16802, USA

2 Huck Institutes of Life Sciences, Pennsylvania State University, University Park, PA 16802, USA

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BMC Evolutionary Biology 2008, 8:260  doi:10.1186/1471-2148-8-260

Published: 24 September 2008

Abstract

Background

All bilaterian animals share a general genetic framework that controls the formation of their body structures, although their forms are highly diversified. The Hox genes that encode transcription factors play a central role in this framework. All Hox proteins contain a highly conserved homeodomain encoded by the homeobox motif, but the other regions are generally assumed to be less conserved. In this study, we used comparative genomic methods to infer possible functional elements in the coding regions of mammalian Hox genes.

Results

We identified a set of ultraconserved coding regions (UCRs) outside the homeobox of mammalian Hox genes. Here a UCR is defined as a region of at least 120 nucleotides without synonymous and nonsynonymous nucleotide substitutions among different orders of mammals. Further analysis has indicated that these UCRs occur only in placental mammals and they evolved apparently after the split of placental mammals from marsupials. Analysis of human SNP data suggests that these UCRs are maintained by strong purifying selection.

Conclusion

Although mammalian genomes are known to contain ultraconserved non-coding elements (UNEs), this paper seems to be the first to report the UCRs in protein coding genes. The extremely high degree of sequence conservation in non-homeobox regions suggests that they might have important roles for the functions of Hox genes. We speculate that UCRs have some gene regulatory functions possibly in relation to the development of the intra-uterus child-bearing system.