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

In the evolutionary model of dosage compensation,per-allele expression level of the X chromosome has been proposed to have twofold up-regulation to compensate its dose reduction in males(XY)compared to females(XX).However,the expression regulation of X-linked genes is still controversial,and comprehensive evaluations are still lacking.By integrating multi-omics datasets in mammals,we investigated the expression ratios including X to autosomes(X:AA ratio)and X to orthologs(X:XX ratio)at the transcriptome,translatome,and proteome levels.We revealed a dynamic spatial-temporal X:AA ratio during development in humans and mice.Meanwhile,by tracing the evolution of orthologous gene expression in chickens,platypuses,and opossums,we found a stable expression ratio of X-linked genes in humans to their autosomal orthologs in other species(X:XX1)across tissues and developmental stages,demonstrating stable dosage compensation in mammals.We also found that different epigenetic regulations contributed to the high tissue specificity and stage specificity of X-linked gene expression,thus affecting X:AA ratios.It could be concluded that the dynamics of X:AA ratios were attributed to the different gene contents and expression preferences of the X chromosome,rather than the stable dosage compensation.