Most humans carry the same genes in their genome. Men and women have slightly different sex chromosomes, however; men carry an X and a Y, while women carry two X chromosomes, one of which is silenced. But how does gene expression differ in males and females? New research has suggested that there are widespread but subtle differences. These differentially expressed genes were also shown to be exerting a significant influence on the risk, severity, prevalence, and age-of-onset of diseases including autoimmune disorders, cancer, cardiovascular disease, and neurological problems.
Throughout the body, cells carry the genome in their nucleus. But they don't all express the same genes; the genes expressed by a cell and the proteins it produces give a cell its identity and enable it to function properly within the context of an organism. While cells in different tissues and organs express genes at different levels, these gene expression levels are also impacted by an organism's sex. In humans, gene expression also varies from one person to another. Gene expression variability between the tissues of men and women is still not well-understood, but it appears to be more dependent on autosomal genes carried by everyone, and less to do with hormones or genes that are specific to a sex.
The Genotype-Tissue Expression (GTEx) consortium used post-mortem tissue samples to conduct large studies on how genes were expressed throughout human tissues. One finding is that variations in gene expression among the sexes are much more common than we knew. Over one-third of known genes showed sex-based differences in their expression in at least one tissue. While these differences can be found across mammals, we don't know how they are connected to disease.
While there are differences in the expression of many genes in various tissues, however, the individual effects for each gene were subtle (the median fold change in expression was only 1.04).
"One of the most striking things about this comprehensive study of sex differences is that while aggregate differences span the genome and contribute to biases in human health, each individual gene varies tremendously between people," noted Melissa Wilson. Wilson is a researcher in the Biodesign Center for Mechanisms in Evolution, the Center for Evolution and Medicine, and ASU's School of Life Sciences, and author of a Perspectives commentary in Science on sex-based gene expression differences found in the GTEx studies.
For many years, these sex-based differences went unexamined. Often, many studies were conducted only with male models to avoid the (often erroneous) assumption that hormonal changes in females would skew the results. As such, there is much to learn about sex differences in gene expression, disease diagnosis, and treatment.