A new study from the Max Planck Institute for Evolutionary Biology in Plön, Germany, and the Biomedical Pioneering Innovation Center at Peking University in Beijing challenges the traditional binary classification of biological sex. Published in the journal eLife, the research indicates that human organs exhibit a mosaic of sex-specific characteristics rather than fitting neatly into male or female categories.
The findings highlight that while germ cells—sperm and eggs—are distinctly categorized, most organs display overlapping patterns of male and female traits. The only organs that remain clearly distinguishable are the testes and ovaries. This complexity is evident in various organs: in mice, significant differences arise in the kidney and liver, while in humans, it is particularly noticeable in adipose tissue. Interestingly, the brain shows minimal differences between sexes in both species, consistent with earlier studies on human brain structure.
To quantify these variations, the researchers developed a Sex-Bias Index (SBI). This index consolidates the activity of male- and female-specific genes within an organ into a single value. While the index reveals a clear distinction in sexual organs, it illustrates that in many other organs, the values are so closely aligned that reliable differentiation between men and women becomes challenging. For example, a man’s heart may exhibit more female-like characteristics than that of some women. Furthermore, within a single individual, different organs may reflect contrasting sex characteristics, such as a more female-like heart alongside a more male-like liver.
Evolutionary Insights on Gene Activity
The research underscores that sex-specific gene activity in various organs evolves rapidly, significantly faster than genes that function equally in both sexes. For instance, between mouse species that diverged less than two million years ago, most genes have either lost or switched their specific roles. This rapid evolution results in a limited number of conserved sex-specific genes when comparing humans and mice, suggesting that mouse models may not be effective for studying sex-specific medical issues in humans.
Additionally, the study found that sex-specific genes often function within “modules” that are co-regulated. Evolutionary changes in sex differences arise not from altering single genes but from reorganizing entire networks. The primary force behind these shifts is sexual selection, which reflects the ongoing evolutionary conflict between male and female interests. This persistent conflict ensures that adaptations continually create new contrasts, further complicating the classification of biological sex.
When analyzing human tissues, the study reveals a marked decrease in sex-specific genes relative to mice, with even greater overlaps observed between men and women. This suggests that in humans, biological differences are less pronounced, further challenging the notion of a strict binary classification.
Reframing Biological Sex
The study concludes that while sexual organs maintain a clear binary distinction, most other tissues function along a continuum of sex-specific gene activity. This dynamic spectrum varies among species and individuals, indicating that biological sex is not rigid or clearly defined. Instead, it is shaped by evolutionary processes and individual differences.
In light of these findings, it is evident that efforts to classify the human body strictly as male or female based on molecular features overlook the intricate complexity of biological sex. The research advocates for a broader understanding of sex as a complex mosaic, urging a reconsideration of how sex characteristics are perceived and categorized in both scientific and medical contexts.
