The human X chromosome has a unique biology shaped by its evolution as the sex chromosome shared by males and females. The authors have determined 99.3% of the euchromatic sequence of the X chromosome, revealing insights into its autosomal origin, the progressive loss of recombination between X and Y chromosomes, and the degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, consistent with their role in X-chromosome inactivation (XCI). The sequence contains 1,098 genes, with 99 encoding proteins expressed in testes and various tumors. A disproportionately high number of mendelian diseases are associated with the X chromosome, with 168 explained by mutations in 113 X-linked genes. The X chromosome has unique features, such as XCI, where one of the two X chromosomes in females is inactivated early in development. In males, the X chromosome fails to recombine during meiosis, except for short regions at the tips of the X chromosome arms that recombine with the Y chromosome. The X chromosome's unique properties are a consequence of the evolution of sex chromosomes in mammals, where the X chromosome has retained functional elements, while the Y chromosome has lost most of its ancestral autosome content. The X chromosome sequence was constructed using P1-artificial chromosome (PAC) and bacterial artificial chromosome (BAC) clones, with gaps closed by targeted screening and assessment of BAC and fosmid end-sequence data. The sequence covers at least 99.3% of the euchromatic region, with 14 euchromatic gaps totaling less than 1 Mb. The sequence is approximately 155 Mb in length. The X chromosome is gene-poor, highly enriched in interspersed repeats, and has a low (G+C) content compared to the genome average. The gene density is among the lowest for annotated chromosomes, with only 1.7% of the sequence occupied by exons. The X chromosome contains the largest known gene, dystrophin, and has a low frequency of CpG islands. Evolutionarily conserved regions (ECRs) are identified, and non-coding RNA genes are annotated, including the XIST gene critical for XCI. The X chromosome contains a significant number of cancer-testis antigen genes, which are expressed in testes and have potential targets for tumor immunotherapy. The X chromosome is also characterized by high repetitive sequence content, particularly LINE1 elements, which may influence XCI. The evolutionary process has eroded the ancestral relationship between the X and Y chromosomes, with limited homology remaining in non-recombining regions. The X chromosome has four major evolutionary strata, with increasing divergence from the Y chromosome moving distally through the strata. The progressive loss of XY recombination has led to the degeneration of the Y chromosome, with only a few genes sharing homologues on both chromosomes. XCI in mammals achieves dosage compensation betweenThe human X chromosome has a unique biology shaped by its evolution as the sex chromosome shared by males and females. The authors have determined 99.3% of the euchromatic sequence of the X chromosome, revealing insights into its autosomal origin, the progressive loss of recombination between X and Y chromosomes, and the degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, consistent with their role in X-chromosome inactivation (XCI). The sequence contains 1,098 genes, with 99 encoding proteins expressed in testes and various tumors. A disproportionately high number of mendelian diseases are associated with the X chromosome, with 168 explained by mutations in 113 X-linked genes. The X chromosome has unique features, such as XCI, where one of the two X chromosomes in females is inactivated early in development. In males, the X chromosome fails to recombine during meiosis, except for short regions at the tips of the X chromosome arms that recombine with the Y chromosome. The X chromosome's unique properties are a consequence of the evolution of sex chromosomes in mammals, where the X chromosome has retained functional elements, while the Y chromosome has lost most of its ancestral autosome content. The X chromosome sequence was constructed using P1-artificial chromosome (PAC) and bacterial artificial chromosome (BAC) clones, with gaps closed by targeted screening and assessment of BAC and fosmid end-sequence data. The sequence covers at least 99.3% of the euchromatic region, with 14 euchromatic gaps totaling less than 1 Mb. The sequence is approximately 155 Mb in length. The X chromosome is gene-poor, highly enriched in interspersed repeats, and has a low (G+C) content compared to the genome average. The gene density is among the lowest for annotated chromosomes, with only 1.7% of the sequence occupied by exons. The X chromosome contains the largest known gene, dystrophin, and has a low frequency of CpG islands. Evolutionarily conserved regions (ECRs) are identified, and non-coding RNA genes are annotated, including the XIST gene critical for XCI. The X chromosome contains a significant number of cancer-testis antigen genes, which are expressed in testes and have potential targets for tumor immunotherapy. The X chromosome is also characterized by high repetitive sequence content, particularly LINE1 elements, which may influence XCI. The evolutionary process has eroded the ancestral relationship between the X and Y chromosomes, with limited homology remaining in non-recombining regions. The X chromosome has four major evolutionary strata, with increasing divergence from the Y chromosome moving distally through the strata. The progressive loss of XY recombination has led to the degeneration of the Y chromosome, with only a few genes sharing homologues on both chromosomes. XCI in mammals achieves dosage compensation between