Characterization of the genomic Xist locus in rodents reveals conservation of overall gene structure and tandem repeats but rapid evolution of unique sequence.

The Xist locus plays a central role in the regulation of X chromosome inactivation in mammals, although its exact mode of action remains to be elucidated. Evolutionary studies are important in identifying conserved genomic regions and defining their possible function. Here we report cloning, sequence analysis, and detailed characterization of the Xist gene from four closely related species of common vole (field mouse), Microtus arvalis. Our analysis reveals that there is overall conservation of Xist gene structure both between different vole species and relative to mouse and human Xist/XIST. Within transcribed sequence, there is significant conservation over five short regions of unique sequence and also over Xist-specific tandem repeats. The majority of unique sequences, however, are evolving at an unexpectedly high rate. This is also evident from analysis of flanking sequences, which reveals a very high rate of rearrangement and invasion of dispersed repeats. We discuss these results in the context of Xist gene function and evolution.

[1]  G. Benson,et al.  Tandem repeats finder: a program to analyze DNA sequences. , 1999, Nucleic acids research.

[2]  J. Landry,et al.  Long Terminal Repeats Are Used as Alternative Promoters for the Endothelin B Receptor and Apolipoprotein C-I Genes in Humans* , 2001, The Journal of Biological Chemistry.

[3]  V. V. Ivanov,et al.  GeneBee-net: Internet-based server for analyzing biopolymers , 1995 .

[4]  J. Mcneil,et al.  XIST RNA paints the inactive X chromosome at interphase: evidence for a novel RNA involved in nuclear/chromosome structure , 1996, The Journal of cell biology.

[5]  H. Willard,et al.  Characterization of a murine gene expressed from the inactive X chromosome , 1991, Nature.

[6]  Carolyn J. Brown,et al.  Evolutionary conservation of possible functional domains of the human and murine XIST genes. , 1993, Human molecular genetics.

[7]  Neil Brockdorff,et al.  Stabilization of Xist RNA Mediates Initiation of X Chromosome Inactivation , 1997, Cell.

[8]  A. G. Shilov,et al.  Demonstration of the X-linkage and order to the genes GLA, G6PD, HPRT, and PGK in two vole species of the genus Microtus. , 1994, Cytogenetics and cell genetics.

[9]  E. Flemington,et al.  CpG methylation as a mechanism for the regulation of E2F activity. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[10]  A. Ashworth,et al.  Expression of Xist during mouse development suggests a role in the initiation of X chromosome inactivation , 1993, Cell.

[11]  D C Ward,et al.  Differential distribution of long and short interspersed element sequences in the mouse genome: chromosome karyotyping by fluorescence in situ hybridization. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[12]  R. Jaenisch,et al.  Long-range cis effects of ectopic X-inactivation centres on a mouse autosome , 1997, Nature.

[13]  M. Gouy,et al.  Molecular phylogeny of Rodentia, Lagomorpha, Primates, Artiodactyla, and Carnivora and molecular clocks. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[14]  S. Rastan,et al.  Requirement for Xist in X chromosome inactivation , 1996, Nature.

[15]  P. Avner,et al.  Cloning and localization of the murine Xpct gene: evidence for complex rearrangements during the evolution of the region around the Xist gene. , 1998, Genomics.

[16]  C. Chen,et al.  A new structure for the murine Xist gene and its relationship to chromosome choice/counting during X-chromosome inactivation. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[17]  M. Meyer,et al.  Non-random inactivation of the X-chromosome in interspecific hybrid voles. , 1987, Genetical research.

[18]  Sudhir Kumar,et al.  Continental breakup and the ordinal diversification of birds and mammals , 1996, Nature.

[19]  B. Cattanach Control of chromosome inactivation. , 1975, Annual review of genetics.

[20]  M. Monk,et al.  XIST expression in human oocytes and preimplantation embryos. , 1997, American journal of human genetics.

[21]  J. Mann,et al.  Quantitative RT-PCR assays show Xist RNA levels are low in mouse female adult tissue, embryos and embryoid bodies. , 1994, Development.

[22]  R. Jaenisch,et al.  A 450 kb Transgene Displays Properties of the Mammalian X-Inactivation Center , 1996, Cell.

[23]  N. Brockdorff,et al.  Xist RNA exhibits a banded localization on the inactive X chromosome and is excluded from autosomal material in cis. , 1999, Human molecular genetics.

[24]  A. Ashworth,et al.  Conservation of position and exclusive expression of mouse Xist from the inactive X chromosome , 1991, Nature.

[25]  N. Stavropoulos,et al.  Further examination of the Xist promoter-switch hypothesis in X inactivation: evidence against the existence and function of a P(0) promoter. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[26]  J. Weissenbach,et al.  A 94 kb genomic sequence 3' to the murine Xist gene reveals an AT rich region containing a new testis specific gene Tsx. , 1996, Human molecular genetics.

[27]  T. Nesterova,et al.  Heterochromatin as a factor affecting X-inactivation in interspecific female vole hybrids ( Microtidae, Rodentia ) , 1991 .

[28]  M. Lyon Gene Action in the X-chromosome of the Mouse (Mus musculus L.) , 1961, Nature.

[29]  Carolyn J. Brown,et al.  A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome , 1991, Nature.

[30]  T. Nesterova,et al.  High-resolution G-banding of chromosomes in Microtus subarvalis (Rodentia, Arvicolidae) , 2004, Hereditas.

[31]  R. Gibbs,et al.  Large-scale comparative sequence analysis of the human and murine Bruton's tyrosine kinase loci reveals conserved regulatory domains. , 1997, Genome research.

[32]  S. Rastan,et al.  The search for the mouse X-chromosome inactivation centre. , 1990, Genetical research.

[33]  Jeannie T. Lee,et al.  Tsix, a gene antisense to Xist at the X-inactivation centre , 1999, Nature Genetics.

[34]  E. Lindsay,et al.  EUCRICETODON ASIATICUS (MATTHEW AND GRANGER), AN OLIGOCENE RODENT (CRICETIDAE) , 1978 .

[35]  W. Strauss,et al.  A revision of the human XIST gene organization and structural comparison with mouse Xist , 2000, Mammalian Genome.

[36]  Brian D. Hendrich,et al.  Identification and characterization of the human XIST gene promoter: implications for models of X chromosome inactivation , 1997, Nucleic Acids Res..

[37]  B. Cattanach,et al.  Controlling elements in the mouse X-chromosome. I. Interaction with the X-linked genes. , 1969, Genetical research.

[38]  S. Rastan,et al.  Regulatory elements in the minimal promoter region of the mouse Xist gene. , 1997, Gene.

[39]  M. Boguski,et al.  Evolutionary parameters of the transcribed mammalian genome: an analysis of 2,820 orthologous rodent and human sequences. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[40]  Alan Ashworth,et al.  Xist has properties of the X-chromosome inactivation centre , 1997, Nature.

[41]  J. Sabina,et al.  Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure. , 1999, Journal of molecular biology.

[42]  R. Jaenisch,et al.  Xist-deficient mice are defective in dosage compensation but not spermatogenesis. , 1997, Genes & development.

[43]  M. Novacek Mammalian phylogeny: shaking the tree. , 1992, Nature.

[44]  W. Miller,et al.  Comparative genome sequence analysis of the Bpa/Str region in mouse and Man. , 2000, Genome research.

[45]  Dominic P. Norris,et al.  The product of the mouse Xist gene is a 15 kb inactive X-specific transcript containing no conserved ORF and located in the nucleus , 1992, Cell.

[46]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[47]  W. Miller,et al.  A time-efficient, linear-space local similarity algorithm , 1991 .

[48]  J. Jurka Repbase update: a database and an electronic journal of repetitive elements. , 2000, Trends in genetics : TIG.

[49]  B. Cattanach,et al.  Controlling elements in the mouse X chromosome. , 1967, Genetics.

[50]  M. Lyon,et al.  X-Chromosome inactivation: a repeat hypothesis , 1998, Cytogenetic and Genome Research.

[51]  D. Lipman,et al.  Improved tools for biological sequence comparison. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[52]  R. Britten,et al.  Rates of DNA sequence evolution differ between taxonomic groups. , 1986, Science.

[53]  B. Cattanach,et al.  Controlling elements in the mouse. IV. Evidence of non-random X-inactivation. , 1981, Genetical research.

[54]  R. Jaenisch,et al.  X Chromosome Inactivation Is Mediated by Xist RNA Stabilization , 1997, Cell.

[55]  N. Brockdorff,et al.  Developmentally Regulated Xist Promoter Switch Mediates Initiation of X Inactivation , 1998, Cell.

[56]  B. Cattanach,et al.  Controlling elements in the mouse X-chromosome. II. Location in the linkage map. , 1970, Genetical research.

[57]  Carolyn J. Brown,et al.  The human XIST gene: Analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus , 1992, Cell.

[58]  A. Bird CpG-rich islands and the function of DNA methylation , 1986, Nature.

[59]  J A Bailey,et al.  Molecular evidence for a relationship between LINE-1 elements and X chromosome inactivation: the Lyon repeat hypothesis. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[60]  P. Ray,et al.  XIST expression from the maternal X chromosome in human male preimplantation embryos at the blastocyst stage. , 1997, Human molecular genetics.

[61]  D. Higgins,et al.  See Blockindiscussions, Blockinstats, Blockinand Blockinauthor Blockinprofiles Blockinfor Blockinthis Blockinpublication Clustal: Blockina Blockinpackage Blockinfor Blockinperforming Multiple Blockinsequence Blockinalignment Blockinon Blockina Minicomputer Article Blockin Blockinin Blockin , 2022 .

[62]  R. Gibbs,et al.  PipMaker--a web server for aligning two genomic DNA sequences. , 2000, Genome research.

[63]  J. V. Moran,et al.  Many human L1 elements are capable of retrotransposition , 1997, Nature Genetics.