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.