Department of Pathology, University of Washington School of Medicine, Seattle, USA.
Nat Genet. 2011 Oct 23;43(12):1179-85. doi: 10.1038/ng.948.
Many animal species use a chromosome-based mechanism of sex determination, which has led to the coordinate evolution of dosage-compensation systems. Dosage compensation not only corrects the imbalance in the number of X chromosomes between the sexes but also is hypothesized to correct dosage imbalance within cells that is due to monoallelic X-linked expression and biallelic autosomal expression, by upregulating X-linked genes twofold (termed 'Ohno's hypothesis'). Although this hypothesis is well supported by expression analyses of individual X-linked genes and by microarray-based transcriptome analyses, it was challenged by a recent study using RNA sequencing and proteomics. We obtained new, independent RNA-seq data, measured RNA polymerase distribution and reanalyzed published expression data in mammals, C. elegans and Drosophila. Our analyses, which take into account the skewed gene content of the X chromosome, support the hypothesis of upregulation of expressed X-linked genes to balance expression of the genome.
许多动物物种使用基于染色体的性别决定机制，这导致了剂量补偿系统的协调进化。剂量补偿不仅纠正了性染色体数量的不平衡，而且据推测还可以通过上调两倍的 X 连锁基因来纠正由于单等位基因 X 连锁表达和双等位基因常染色体表达而导致的细胞内剂量失衡（称为“大野的假说”）。虽然该假说得到了单个 X 连锁基因的表达分析和基于微阵列的转录组分析的很好支持，但最近的一项使用 RNA 测序和蛋白质组学的研究对其提出了挑战。我们获得了新的、独立的 RNA-seq 数据，测量了 RNA 聚合酶的分布，并重新分析了哺乳动物、秀丽隐杆线虫和果蝇中已发表的表达数据。我们的分析考虑了 X 染色体的偏斜基因含量，支持上调表达的 X 连锁基因以平衡基因组表达的假说。
