Dynamic Spatial-Temporal Expression Ratio of X Chromosome to Autosomes but Stable Dosage Compensation in Mammals

Abstract

In the evolutionary model of dosage compensation, per-allele expression level of the X chromosome was proposed to have two-fold upregulation, compensating for its dose reduction in males (XY) compared to females (XX). However, the upregulation of X chromosome is still in dispute, and comprehensive evaluations are still lacking. By integrating multi-omics datasets in mammals, we investigated the expression ratios and underlying pattern of X to autosomes (X:AA ratio) and X to orthologs (X:XX ratio) at the transcriptome, translatome, and proteome layers. The results indicated a dynamic spatial-temporal X:AA ratio during development in human and mouse. Meanwhile, by tracing the evolution of orthologous gene expressions in chicken, platypus, and opossum, we found a constant expression ratio between X-linked genes in human and their autosomal orthologs in other species (X:XX ~1) across tissues and developmental stages, demonstrating stable dosage compensation in mammals. We also revealed that different epigenetic regulations could shape the higher tissue- and stage-specificity of X-linked gene expression, and affect X:AA ratios. We conclude that the dynamics of X:AA ratios are attributed to the different gene contents and expression preferences of the X chromosome, instead of the stable dosage compensation.