A Dual Origin of the Xist Gene Table 3. Tandem repeats in the Xist gene. No 1. 2. 3. 4. 5. 6. 7. 8. Repeat name, exon A exon 1 F exon 1 Bh exon 1 B exon 1 H exon 1 C exon 1 D exon 1 Description Repeat A is present in all the species studied and is the most important region of the RNA for chromosome silencing. It has a monomer with an average size of about 50 bp. The copy number varies from six to nine. This repeat consists of two parts—constant GC-rich and variable AT-rich. Repeat F is not purely a tandem repeat and is detectable in all species only as a 19-bp motif. Its copy number varies from two to five. This region in mouse carries the P2 promoter. Repeat Bh is detectable only in primates; it is a small microsatellite tract, (C)5–8A Repeat B is also a microsatellite tract, (CCCCAG)n; it is present in all the species. Repeat H is a small block of tandem repeats with a monomer unit of 33 bp, which is detected in the consensus gene and is most pronounced in dog. The monomers in contemporary species have diverged beyond recognition. Repeat C is a block of tandem repeats with a monomer of 11 bp and copy number of 14 present only in mouse and rat. In other species including rather closely related voles, only one incomplete monomer is detected. References [11, 17 26, 27, 28] [15] [15] [15,26,27,28] [15,26,27,28] Repeat D is the largest and most obscure. Monomers have mutated considerably and lost their [15,26,27,28] similarity during evolution; however, fragments of mutated monomers with various length reamplified in even-hoofed ungulates, carnivores, and primates. The monomer with a length of 290 bp amplified in primates. Bovine displays three different blocks of D repeats with the monomers of 93, 95, and 189 bp. Two similar 94-bp monomers amplified in dog. All the consensuses of the monomers in different species are relatively homologous; however, considerably distinct variants are also found. This repeat forms an essential part of exon 1 in human, chimpanzee, dog, and bovine. Possible origin endogenous retroviruses DNA transposons L1 LINE endogenous retroviruses endogenous retroviruses E exon h6/m7 Repeat E is the most variable repeat present in all the species. Its monomer is 30–25 bp long, AT-rich, and not distinct. [15,26,27,28] Intracisternal A particle (IAP) doi:10.1371/journal.pone.0002521.t003 Tandem repeats in Xist originated from mobile elements The majority of Xist exon 1 consensus consists of various tandem repeats (A–F), which may represent up to 78% of the exon, as observed in bovine Xist (Table S1). The beginning of exon h6/m7 also contains a tandem repeat E (Fig. 1, Table 3). Using the program TRF4, we deduced the consensus sequences for the main blocks of tandem repeats in the Xist gene and compared the consensus dimers with the database of dispersed repeats (RepBase). This analysis revealed that repeats A, C, and D display a similarity to different classes of endogenous retroviruses (Table 4, Fig. S4). Three similar variants of repeat F are detectable in the Xist gene consensus and they all display some similarity to DNA transposons. The ancient block of H repeats, which we identified in the Xist consensus sequence, displays a high similarity to the 39 end of marsupial (M. domestica) LINE L1-7_MD L1. Repeat B is a microsatellite tract (CCCCAG)n, which is found in dispersed repeats and could have been introduced, for example, with the same endogenous retroviruses (Table 4, Fig. S4). It should be noted that a Figure 2. Comparison of the chicken Lnx3 –Fip1l2 genomic region with the human XIST, 39-flank and pseudo-TSX region. Homologous regions are indicated by arrows. Positions are shown in base pairs. Coloured boxes represent exons; yellow, pseudoexons; and blue, 59-UTR. doi:10.1371/journal.pone.0002521.g002 PLoS ONE | www.plosone.org 4 June 2008 | Volume 3 | Issue 6 | e2521