The evolution of heteromorphic sex chromosomes shall lead to gene expression dosage problems, as in at least one of the sexes, the sex-linked gene dose has been reduced by half. It has been proposed that the transcriptional output of the whole X or Z chromosome should be doubled for complete dosage compensation in heterogametic sex. However, owing to the variability of the existing methods to determine the transcriptional differences between sex chromosomes and autosomes (S:A ratios) in different studies, we collected more than 500 public RNA-Seq data set from multiple tissues and species in major clades and proposed a unified computational framework for unbiased and comparable measurement of the S:A ratios of multiple species. We also tested the evolution of dosage compensation more directly by assessing changes in the expression levels of the current sex-linked genes relative to those of the ancestral sex-linked genes. We found that in mammals and birds, the S:A ratio is approximately 0.5, whereas in insects, fishes, and flatworms, the S:A ratio is approximately 1.0. Further analysis showed that the fraction of dosage-sensitive housekeeping genes on the X/Z chromosome is significantly correlated with the S:A ratio. In addition, the degree of degeneration of the Y chromosome may be responsible for the change in the S:A ratio in mammals without a dosage compensation mechanism. Our observations offer unequivocal support for the sex chromosome insensitivity hypothesis in animals and suggest that dosage sensitivity states of sex chromosomes are a major factor underlying different evolutionary strategies of dosage compensation.

异形性染色体的进化会导致基因表达剂量问题，因为至少在一种性别中，性相关基因剂量已经减少了一半。已经提出整个 X 或 Z 染色体的转录输出应该加倍以实现异配性的完全剂量补偿。然而，由于在不同研究中确定性染色体和常染色体（S:A 比率）之间转录差异的现有方法存在差异，我们从主要进化枝的多个组织和物种中收集了 500 多个公共 RNA-Seq 数据集和提出了一个统一的计算框架，用于对多个物种的 S:A 比率进行无偏和可比较的测量。我们还通过评估当前性相关基因相对于祖先性相关基因表达水平的变化，更直接地测试了剂量补偿的演变。我们发现，在哺乳动物和鸟类中，S:A 比率约为 0.5，而在昆虫、鱼类和扁虫中，S:A 比率约为 1.0。进一步分析表明，X/Z 染色体上剂量敏感管家基因的比例与 S:A 比显着相关。此外，在没有剂量补偿机制的哺乳动物中，Y 染色体的退化程度可能是导致 S:A 比率变化的原因。