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Open Access Highly Accessed Research article

Evolution of coding and non-coding genes in HOX clusters of a marsupial

Hongshi Yu12, James Lindsay3, Zhi-Ping Feng45, Stephen Frankenberg12, Yanqiu Hu12, Dawn Carone3, Geoff Shaw12, Andrew J Pask123, Rachel O’Neill3, Anthony T Papenfuss46 and Marilyn B Renfree12*

Author Affiliations

1 ARC Centre of Excellence in Kangaroo Genomics, The University of Melbourne, Melbourne, Victoria, 3010, Australia

2 Department of Zoology, The University of Melbourne, Melbourne, Victoria, 3010, Australia

3 Department of Molecular and Cell Biology, College of Liberal Arts and Sciences, University of Connecticut, Connecticut, CT, 06269, USA

4 Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia

5 Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, 3010, Australia

6 Department of Mathematics and Statistics, The University of Melbourne, Melbourne, Victoria, 3010, Australia

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BMC Genomics 2012, 13:251  doi:10.1186/1471-2164-13-251

Published: 18 June 2012



The HOX gene clusters are thought to be highly conserved amongst mammals and other vertebrates, but the long non-coding RNAs have only been studied in detail in human and mouse. The sequencing of the kangaroo genome provides an opportunity to use comparative analyses to compare the HOX clusters of a mammal with a distinct body plan to those of other mammals.


Here we report a comparative analysis of HOX gene clusters between an Australian marsupial of the kangaroo family and the eutherians. There was a strikingly high level of conservation of HOX gene sequence and structure and non-protein coding genes including the microRNAs miR-196a, miR-196b, miR-10a and miR-10b and the long non-coding RNAs HOTAIR, HOTAIRM1 and HOXA11AS that play critical roles in regulating gene expression and controlling development. By microRNA deep sequencing and comparative genomic analyses, two conserved microRNAs (miR-10a and miR-10b) were identified and one new candidate microRNA with typical hairpin precursor structure that is expressed in both fibroblasts and testes was found. The prediction of microRNA target analysis showed that several known microRNA targets, such as miR-10, miR-414 and miR-464, were found in the tammar HOX clusters. In addition, several novel and putative miRNAs were identified that originated from elsewhere in the tammar genome and that target the tammar HOXB and HOXD clusters.


This study confirms that the emergence of known long non-coding RNAs in the HOX clusters clearly predate the marsupial-eutherian divergence 160 Ma ago. It also identified a new potentially functional microRNA as well as conserved miRNAs. These non-coding RNAs may participate in the regulation of HOX genes to influence the body plan of this marsupial.

Marsupial; HOX cluster; MicroRNAs; Long non-coding RNAs