Susumu Ohno proposed that the gene content of the mammalian X Chromosome should remain highly conserved due to dosage compensation. X Chromosome linkage (gene order) conservation is widespread in placental mammals but does not fall within the scope of Ohno's prediction and may be an indirect result of selection on gene content or selection against rearrangements that might disrupt X-Chromosome inactivation (XCI). Previous comparisons between the human and mouse X Chromosome sequences have suggested that although single-copy X Chromosome genes are conserved between species, most ampliconic genes were independently acquired. To better understand the evolutionary and functional constraints on X-linked gene content and linkage conservation in placental mammals, we aligned a new, high-quality, long-read X Chromosome reference assembly from the domestic cat (incorporating 19.3 Mb of targeted BAC clone sequence) to the pig, human, and mouse assemblies. A comprehensive analysis of annotated X-linked orthologs in public databases demonstrated that the majority of ampliconic gene families were present on the ancestral placental X Chromosome. We generated a domestic cat Hi-C contact map from an F1 domestic cat/Asian leopard cat hybrid and demonstrated the formation of the bipartite structure found in primate and rodent inactivated X Chromosomes. Conservation of gene order and recombination patterns is attributable to strong selective constraints on three-dimensional genomic architecture necessary for superloop formation. Species with rearranged X Chromosomes retain the ancestral order and relative spacing of loci critical for superloop formation during XCI, with compensatory inversions evolving to maintain these long-range physical interactions.

中文翻译：

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基因组结构限制胎盘哺乳动物 X 染色体进化

Susumu Ohno 提出，由于剂量补偿，哺乳动物 X 染色体的基因含量应保持高度保守。X 染色体连锁（基因顺序）保守性在胎盘哺乳动物中很普遍，但不属于 Ohno 预测的范围，可能是选择基因内容或选择可能破坏 X 染色体失活 (XCI) 的重排的间接结果。先前人类和小鼠 X 染色体序列之间的比较表明，尽管单拷贝 X 染色体基因在物种之间是保守的，但大多数扩增基因是独立获得的。为了更好地了解胎盘哺乳动物中 X 连锁基因含量和连锁保守的进化和功能限制，我们对齐了一个新的、高质量、从家猫（包含 19.3 Mb 的靶向 BAC 克隆序列）到猪、人类和小鼠组装的长读 X 染色体参考组装。对公共数据库中带注释的 X 连锁直系同源物的综合分析表明，大多数扩增基因家族存在于祖先胎盘 X 染色体上。我们从 F1 家猫/亚洲豹猫杂种中生成了家猫 Hi-C 接触图，并证明了在灵长类动物和啮齿动物失活的 X 染色体中发现的二分结构的形成。基因顺序和重组模式的保守归因于对超级环形成所必需的三维基因组结构的强选择性限制。