RNA-Seq reveals how sex affects gene expression in mammals

Researchers report the discovery of genome-wide variations in gene expression between mammalian females and males and offer new insights into the molecular origins and evolution of sexual dimorphism in mammal species, according to a new study. The findings could help explain the wide range of sex-specific differences in human health and disease. Female and male mammals often exhibit a variety of differences in biological processes and phenotypic traits. For example, in most mammal species males are larger than females, and because sex differences appear common across many species, animal models are often used to investigate sex-biased traits and diseases in humans. However, the effects of sex on gene expression, particularly in autosomal genes, aren’t well known.

To investigate how sex affects the genome, Researchers from the Whitehead Institute performed a genome-wide, multi-tissue and comparative survey of sex-biased gene expression across five mammalian species. They collected RNA sequencing data from male and female macaques, mice, rats and dogs for 12 different tissues which represented each germ layer as well as most major organ systems. Non-human data was compared to corresponding human RNA-seq data from the Genotype Tissue Expression Consortium (GTEx), which catalogs gene expression across all major tissues in the human body.

The comparative analyses revealed hundreds of conserved sex-biased gene expressions in each tissue, which contribute to differences in traits between the sexes. For example, nearly 12% of the sex difference observed in average human height can be accounted for through conserved sex biases in gene expression. The results also show, however, that most sex bias in gene expression is an evolutionarily recent adaptation and thus is not shared between all mammalian lineages – findings which warrant careful attention in the use of non-human models of sex differences.

RNA sequencing of male and female samples in 12 tissues and five species reveals the functional impact and mechanistic underpinnings of sex-biased gene expression


A survey of sex differences in gene expression using RNA sequencing data (left) leads to the discovery of both conserved (species-shared) and lineage- or species-specific sex biases in expression across the genome. Genes with conserved sex bias contribute to the sex difference in mean height in humans and other mammals, whereas lineage-specific changes can be partially explained by gains and losses of motifs for sex-biased TFs.

Source – Eurekalert

Naqvi S, Godfrey AK, Hughes JF, Goodheart ML, Mitchell RN4, Page DC. (2019) Conservation, acquisition, and functional impact of sex-biased gene expression in mammals. Science 365(6450). [article]

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