Quantitative analysis of Y-Chromosome gene expression across 36 human tissues

Abstract

Little is known about how human Y-Chromosome gene expression directly contributes to differences between XX (female) and XY (male) individuals in nonreproductive tissues. Here, we analyzed quantitative profiles of Y-Chromosome gene expression across 36 human tissues from hundreds of individuals. Although it is often said that Y-Chromosome genes are lowly expressed outside the testis, we report many instances of elevated Y-Chromosome gene expression in a nonreproductive tissue. A notable example is EIF1AY , which encodes eukaryotic translation initiation factor 1A Y-linked, together with its X-linked homolog EIF1AX . Evolutionary loss of a Y-linked microRNA target site enabled up-regulation of EIF1AY , but not of EIF1AX , in the heart. Consequently, this essential translation initiation factor is nearly twice as abundant in male as in female heart tissue at the protein level. Divergence between the X and Y Chromosomes in regulatory sequence can therefore lead to tissue-specific Y-Chromosome-driven sex biases in expression of critical, dosage-sensitive regulatory genes.