A Dual Origin of the Xist Gene Figure 1. Organization of the Xist gene in seven eutherian species and the Xist gene consensus. Grey rectangles represent exons; green, pseudoexons (pEx); blue arrows, LINEs; and red, SINEs; brown rectangles indicate tandem repeats (for details see table 3); black rectangles, CpG- islands. Note that in chimpanzee Xist gene tandem repeats (B, Bh and C) are not detected possibly due to gaps in sequence. Pseudoexon (pEx) means a part of an intronic sequence that is present in other species as an exon. doi:10.1371/journal.pone.0002521.g001 9, and 10 to mobile elements varies from 59 to 64%. All similarities found are statistically significant (Table 4). This is also the case for the degree of similarity between consensus exons 5, 6, and 7, and the exons of the Lnx3 gene. Thus, we have shown that Xist consensus exons 2–4 and 8–10 share some homology with different classes of mobile elements (Fig. S3). Additionally, our data suggests that after the divergence of the main mammalian taxa, young species-specific repeats (Alu of primates, B1 and B2 of rodents, etc.) and pseudogenes were integrated in the Xist gene (Fig. 1). Some young taxon-specific SINEs were inserted in exon 1 and are now present in the processed Xist transcript. Interestingly, Xist CpG islands show a unique distribution in each species and are predominantly coincide with the insertion of species-specific mobile elements (Fig. 1). Table 2. Correspondences between consensus, mouse and human Xist elements and their putative origin. Xist elements Pmin Human XIST Pmin Intron 4 Intron 3 c1 c2 c3 c4 c5 c6 c7 c8 c9 c10 h1 ph2 h2 h3 h4 ph5 h5 h6 h7 h8 Mouse Xist Pmin Intron 3 m1 m2 - m3 m4 m5 m6 m7 pm7 m8 Origin from Lnx3 Exon 1, Exon 2 Exon 2 Exon 3 Exon 4 Exon 5 Exon11 Origin from transposable elements TR, TE LINE, L3CR1 LINE, L1MC3 LINE, L1 TR, TE Fragment of ERV Fragment of DNA transposon Notes. Abbreviations: exons of the mammalian consensus gene – (c1–c10), human and mouse exons, respectively – (h1/m1 – h8/m8); pseudoexons – (ph, pm). Minimal promoter – (Pmin). Tandem repeats – (TR), transposable elements – (TE), endogenous retrovirus – (ERV). Pseudoexon (pEx) means a part of an intronic sequence which is present in other species as an exon. doi:10.1371/journal.pone.0002521.t002 PLoS ONE | www.plosone.org 3 June 2008 | Volume 3 | Issue 6 | e2521