Random X chromosome inactivation (XCI), the eutherian mechanism of X-linked gene 
dosage compensation, is controlled by a cis-acting locus termed the 
X-inactivation center (Xic). One of the striking features that characterize the 
Xic landscape is the abundance of loci transcribing non-coding RNAs (ncRNAs), 
including Xist, the master regulator of the inactivation process. Recent 
comparative genomic analyses have depicted the evolutionary scenario behind the 
origin of the X-inactivation center, revealing that this locus evolved from a 
region harboring protein-coding genes. During mammalian radiation, this 
ancestral protein-coding region was disrupted in the marsupial group, whilst it 
provided in eutherian lineage the starting material for the non-translated RNAs 
of the X-inactivation center. The emergence of non-coding genes occurred by a 
dual mechanism involving loss of protein-coding function of the pre-existing 
genes and integration of different classes of mobile elements, some of which 
modeled the structure and sequence of the non-coding genes in a species-specific 
manner. The rising genes started to produce transcripts that acquired function 
in regulating the epigenetic status of the X chromosome, as shown for Xist, its 
antisense Tsix, Jpx, and recently suggested for Ftx. Thus, the appearance of the 
Xic, which occurred after the divergence between eutherians and marsupials, was 
the basis for the evolution of random X inactivation as a strategy to achieve 
dosage compensation.