Non-coding divergence of the human X and Y chromosomes drove male-biased expression of dosage-sensitive regulators

ABSTRACT: Little is known about how Y-chromosome gene expression directly contributes to differences between XX (female) and XY (male) individuals in non-reproductive tissues. It is often said that Y-chromosome genes show low expression outside the testis. Here, we analyzed quantitative profiles of Y-chromosome gene expression across 36 human tissues from hundreds of individuals and report many instances where a Y-chromosome gene shows upregulated expression in a non-reproductive tissue. A notable example is EIF1AY, which encodes eukaryotic initiation factor 1A (EIF1A), together with its X-linked homolog EIF1AX. Evolutionary loss of a Y-linked microRNA target site enabled upregulation of EIF1AY, but not EIF1AX, in the heart. As a result, 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.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Heart

SUBMITTER: Joel Chick  

LAB HEAD: Steven Gygi

PROVIDER: PXD017055 | Pride | 2021-09-09

REPOSITORIES: Pride