, Volume 121, Issue 5, pp 489–497 | Cite as

Evolution of DUX gene macrosatellites in placental mammals

  • Andreas Leidenroth
  • Jannine Clapp
  • Laura M. Mitchell
  • Daniel Coneyworth
  • Frances L. Dearden
  • Leopoldo Iannuzzi
  • Jane E. Hewitt
Research Article


Macrosatellites are large polymorphic tandem arrays. The human subtelomeric macrosatellite D4Z4 has 11–150 repeats, each containing a copy of the intronless DUX4 gene. DUX4 is linked to facioscapulohumeral muscular dystrophy, but its normal function is unknown. The DUX gene family includes DUX4, the intronless Dux macrosatellites in rat and mouse, as well as several intron-containing members (DUXA, DUXB, Duxbl, and DUXC). Here, we report that the genomic organization (though not the syntenic location) of primate DUX4 is conserved in the Afrotheria. In primates and Afrotheria, DUX4 arose by retrotransposition of an ancestral intron-containing DUXC, which is itself not found in these species. Surprisingly, we discovered a similar macrosatellite organization for DUXC in cow and other Laurasiatheria (dog, alpaca, dolphin, pig, and horse), and in Xenarthra (sloth). Therefore, DUX4 and Dux are not the only DUX gene macrosatellites. Our data suggest a new retrotransposition-displacement model for the evolution of intronless DUX macrosatellites.

Supplementary material

412_2012_380_Fig6_ESM.jpg (78 kb)
Online resource 1

DUX4 telomeric macrosatellites are present in the Afrotheria (JPEG 77 kb)

412_2012_380_MOESM1_ESM.tif (4.3 mb)
High resolution image (TIFF 4447 kb)
412_2012_380_Fig7_ESM.jpg (29 kb)
Online resource 2

mrCaNaVaR copy-number analysis. a Pulsed-field gel and Southern blot of HapMap subject NA18507 to show DUX4 copy number. The EcoRI excises all four D4Z4 arrays (two on 4q35, two on 10q26). As EcoRI does not cut within the arrays, an internal probe (p13E-11) can be used to show the size of the entire macrosatellite. The four alleles are approximately 160, 74, 35, and 31 kb in length. From these sizes, we subtract 6.9 kb of flanking sequence that is also within each EcoRI fragment, leaving D4Z4 repeat arrays of 153.1, 67.1, 28.1, and 24.1 kb. These can be added up and divided by 3.3 kb to predict a total DUX4 copy number of ~82. b The graph shows the GC normalization applied by mrCaNaVaR for the Fleckvieh dataset. At the extreme ends of GC content, read-depth is systematically underestimated due to poor representation of such inserts in the sequencing library. After correction, the true read-depth is estimated to be higher (JPEG 28 kb)

412_2012_380_MOESM2_ESM.tif (4.3 mb)
High resolution image (TIFF 4438 kb)
412_2012_380_MOESM3_ESM.docx (31 kb)
Online resource 3mrCaNaVaR results for four different cattle breeds (DOCX 31 kb)
412_2012_380_MOESM4_ESM.docx (31 kb)
Online resource 4DUXC trace archive analysis in other Laurasiatheria (DOCX 31 kb)


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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Andreas Leidenroth
    • 1
  • Jannine Clapp
    • 1
  • Laura M. Mitchell
    • 1
  • Daniel Coneyworth
    • 1
  • Frances L. Dearden
    • 2
  • Leopoldo Iannuzzi
    • 3
  • Jane E. Hewitt
    • 1
  1. 1.Centre for Genetics and Genomics, School of BiologyThe University of NottinghamNottinghamUK
  2. 2.Centre for Veterinary Science, Department of Veterinary MedicineUniversity of CambridgeCambridgeUK
  3. 3.National Research Council (CNR)Institute of Animal Production Systems in Mediterranean Environments (ISPAAM)NaplesItaly

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