A family history of DUX4: phylogenetic analysis of DUXA, B, C and Duxbl reveals the ancestral DUXgene

BMC Evolutionary Biology

Research Article

Andreas Leidenroth¹  Jane E Hewitt¹ 

[1] Centre for Genetics and Genomics, School of Biology, The University of Nottingham, Queens Medical Centre, NG7 2UH, Nottingham, UK;

关键词: Placental Mammal;    Syntenic Region;    Deletion Breakpoint;    Stop Codon Mutation;    Large Open Reading Frame;   

DOI  :  10.1186/1471-2148-10-364

 received in 2010-08-27, accepted in 2010-11-26,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundDUX4 is causally involved in the molecular pathogenesis of the neuromuscular disorder facioscapulohumeral muscular dystrophy (FSHD). It has previously been proposed to have arisen by retrotransposition of DUXC, one of four known intron-containing DUX genes. Here, we investigate the evolutionary history of this multi-member double-homeobox gene family in eutherian mammals.ResultsOur analysis of the DUX family shows the distribution of different homologues across the mammalian class, including events of secondary loss. Phylogenetic comparison, analysis of gene structures and information from syntenic regions confirm the paralogous relationship of Duxbl and DUXB and characterize their relationship with DUXA and DUXC. We further identify Duxbl pseudogene orthologues in primates. A survey of non-mammalian genomes identified a single-homeobox gene (sDUX) as a likely representative homologue of the mammalian DUX ancestor before the homeobox duplication. Based on the gene structure maps, we suggest a possible mechanism for the generation of the DUX gene structure.ConclusionsOur study underlines how secondary loss of orthologues can obscure the true ancestry of individual gene family members. Their relationships should be considered when interpreting the relevance of functional data from DUX4 homologues such as Dux and Duxbl to FSHD.

【 授权许可】

CC BY   
© Leidenroth and Hewitt; licensee BioMed Central Ltd. 2010