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The search for a marsupial XIC reveals a break with vertebrate synteny

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Abstract

X-chromosome inactivation (XCI) evolved in mammals to deal with X-chromosome dosage imbalance between the XX female and the XY male. In eutherian mammals, random XCI of the soma requires a master regulatory locus known as the ‘X-inactivation center’(XIC/Xic), wherein lies the noncoding XIST/Xist silencer RNA and its regulatory antisense Tsix gene. By contrast, marsupial XCI is imprinted to occur on the paternal X chromosome. To determine whether marsupials and eutherians share the XIC-driven mechanism, we search for the sequence equivalents in the genome of the South American opossum, Monodelphis domestica. Positional cloning and bioinformatic analysis reveal several interesting findings. First, protein-coding genes that flank the eutherian XIC are well-conserved in M. domestica, as well as in chicken, frog, and pufferfish. However, in M. domestica we fail to identify any recognizable XIST or TSIX equivalents. Moreover, cytogenetic mapping shows a surprising break in synteny with eutherian mammals and other vertebrates. Therefore, during the evolution of the marsupial X chromosome, one or more rearrangements broke up an otherwise evolutionarily conserved block of vertebrate genes. The failure to find XIST/TSIX in M. domestica may suggest that the ancestral XIC is too divergent to allow for detection by current methods. Alternatively, the XIC may have arisen relatively late in mammalian evolution, possibly in eutherians with the emergence of random XCI. The latter argues that marsupial XCI does not require XIST and opens the search for alternative mechanisms of dosage compensation.

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Authors and Affiliations

  1. Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, 02114, USA

    Lance S. Davidow & Jeannie T. Lee

  2. Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, 27606, USA

    Matthew Breen & Shannon E. Duke

  3. Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, NC, 27606, USA

    Matthew Breen

  4. Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, 4458 TAMU, College Station, TX, 77843-4458, USA

    Paul B. Samollow

  5. Department of Biology, University of Texas at San Antonio, San Antonio, TX, USA

    John R. McCarrey

  6. Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, Boston, MA, 02114, USA

    Jeannie T. Lee

Authors
  1. Lance S. Davidow
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  2. Matthew Breen
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  3. Shannon E. Duke
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  4. Paul B. Samollow
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  5. John R. McCarrey
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  6. Jeannie T. Lee
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Correspondence to Jeannie T. Lee.

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Davidow, L.S., Breen, M., Duke, S.E. et al. The search for a marsupial XIC reveals a break with vertebrate synteny. Chromosome Res 15, 137–146 (2007). https://doi.org/10.1007/s10577-007-1121-6

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  • DOI: https://doi.org/10.1007/s10577-007-1121-6

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