Sex-biased genes and sex-biased gene expression indices for data from human tissues. Credit: eLife (2025). DOI: 10.7554/elife.99602.4

Biological sex is usually described in simple binary terms: male or female. This works well for germ cells (sperm versus eggs), but for other body organs it is of little help.

A new study by the Max Planck Institute for Evolutionary Biology in Plön and the Biomedical Pioneering Innovation Center at Peking University in Beijing, China, shows that our organs form a mosaic of sex-specific characteristics—far removed from the strict division into male and female.

The research shows that in many organs, sex-specific patterns overlap strongly. Only testes and ovaries are clearly distinguishable. All other organs show mosaic-like combinations of male and female characteristics.

Sex-specific stand out most strongly in the sexual organs. But in other organs the picture is more complex. In mice, the kidney and liver show large differences, while in humans it is . By contrast, the brain shows only minimal differences in both species—consistent with previous studies of human brain structure.

To capture this diversity, the researchers developed a Sex-Bias Index (SBI). This index summarizes the activity of all male- and female-specific genes in an organ into a single value. While the index shows a clear separation in the sexual organs, in other organs the values are often so close that men and women cannot be distinguished reliably.

For example, a man's heart may be more "female-like" than that of some women. Even within an individual, organs can differ—the heart more female, the liver more male. This results in a mosaic of sex characteristics that contradicts the idea of a clear-cut binary.

Evolutionary dynamics: Why differences shift so quickly

The study, in eLife, also shows that sex-specific gene activity in organs evolves very rapidly—much faster than genes active in both sexes equally. Even between mouse species that diverged less than 2 million years ago, the majority of genes have lost or even switched their sex-specific role.

As a result, when comparing humans and mice, only very few genes retain conserved sex-specific activity. This also means that mouse models are of very limited use when applied to sex-specific medicine in humans.

The researchers further found that sex-specific genes often occur in "modules" that are regulated together. Evolution therefore alters sex differences not by changing single genes, but by rearranging whole networks. The here is —the ongoing evolutionary conflict between the interests of males and females. This conflict can never be fully resolved, as every adaptation creates new contrasts.

When applied to human tissues, the method reveals a clear pattern: markedly fewer sex-specific genes than in mice, and even stronger overlaps between men and women. In our species, differences are therefore weaker, further undermining the idea of a strict binary classification.

The study concludes that while the sexual organs show a clear binary pattern, most other tissues display a continuum of sex-specific gene activity—a dynamic spectrum that varies both between species and between individuals.

Sex is therefore not rigid and clear-cut, but shaped by evolution, overlaps and individual differences. Instead of classifying the body strictly as male or female based on molecular features, it should be understood as a complex mosaic.

More information: Chen Xie et al, Fast evolutionary turnover and overlapping variances of sex-biased gene expression patterns defy a simple binary sex classification of somatic tissues, eLife (2025).

Journal information: eLife

Provided by Max Planck Society