Summary: Evolutionary inheritance shaped by millions of years of sexual selection appears to favor traits that promote early male reproductive success, sometimes at the cost of later-life health. This imbalance helps explain why men are more susceptible to a range of physical and mental disorders, while women tend to live longer and resist certain conditions.
Source: McMaster University
New analysis by genetics researchers suggests evolutionary forces produce a striking sex bias in many health conditions, including autism.
A team of evolutionary geneticists argues that the human genome has been shaped to favor different inherited traits in males and females. Those sex-specific patterns of inheritance and gene expression make men, on average, more vulnerable to a broad set of physical and mental health problems, and contribute to their shorter life expectancy compared with women, the researchers report in the Journal of Molecular Evolution.
The study notes that some diseases affect women exclusively or predominantly—cervical and ovarian cancers or autoimmune disorders such as multiple sclerosis, for example—yet across many conditions men show higher incidence and severity. The authors link this pattern to long-term evolutionary processes that prioritized male reproductive success early in life.
“Our cells record the legacy of ancestral changes that accumulated over millions of years,” says Rama Singh, a biology professor at McMaster University and corresponding author of the paper. He co-authored the study with Karun Singh, an associate professor of neuropathology at the University of Toronto, and Shiva Singh, a biology professor at Western University.
To illustrate these principles, the researchers examine autism as a clear example of sex-biased health outcomes. Although males and females inherit the same basic genetic blueprint, the way genes are regulated and expressed differs markedly between sexes, producing divergent developmental trajectories and disease risks.
“If males and females were any more different, they would be different species,” the authors note wryly, underscoring the depth of biological divergence that exists despite shared ancestry.
Their work contributes to a growing research movement that applies evolutionary genomics to human health, using inherited patterns to better understand current population-level risks and to guide future medical research.
“Geneticists and evolutionary biologists bring a perspective that is often underrepresented in clinical literature,” says Karun Singh. “Viewing disease through an evolutionary lens helps explain why sex differences in health persist and how they might inform prevention and treatment.”
The authors propose that male-driven evolutionary pressures—especially sexual selection favoring early reproductive advantages—have produced genetic trade-offs: traits that promote early male fitness can have negative pleiotropic effects later in life. These trade-offs can increase male vulnerability to mutations, epigenetic changes, and developmental disruptions that manifest as disease.
Although human social behavior around mate selection has changed, the underlying genetic tendencies remain and continue to influence modern male health. In contrast, female genomes have evolved compensatory responses—stronger immunity and other protective mechanisms—that reduce female susceptibility to many conditions and raise the threshold for disorders such as autism.
Mental health outcomes are shaped by the same evolutionary dynamics, though their causes are complex and multifactorial. For instance, women have higher rates of mood disorders such as depression and anxiety, while men are more often diagnosed with antisocial disorders. Autism shows a pronounced male bias: boys are up to four times more likely to be diagnosed and frequently present with more severe symptoms.
The authors suggest that evolution has set a higher protective threshold in females, making them less likely to cross the genetic or developmental thresholds that lead to autism. Boys, by contrast, inherit a larger number of genetic and epigenetic risk pathways that interact with environmental and developmental factors, increasing their overall vulnerability.
About this ASD and genetics research news
Source: McMaster University
Contact: Wade Hemsworth – McMaster University
Image: The image is in the public domain
Original Research: Open access. “Origin of Sex-Biased Mental Disorders: An Evolutionary Perspective” by Rama S. Singh, Karun K. Singh, Shiva M. Singh. Journal of Molecular Evolution.
Abstract
Origin of Sex-Biased Mental Disorders: An Evolutionary Perspective
Sex differences in disease incidence and mental disorders arise from two primary biological sources: sexual selection and sex hormones. This review synthesizes decades of molecular research on sex-biased gene variation and evolution and places those findings within a theoretical framework that explains sex differences in disease risk and health.
The proposed Sexual Selection–Sex Hormone theory argues that male-driven evolutionary processes, including sexual selection, lead to several outcomes: increased male vulnerability through negative pleiotropic effects tied to traits that enhance early male fitness; higher rates of male-driven mutations and epimutations as a trade-off for early reproductive success; and enhanced female immunity evolving in response to male-beneficial but female-harmful mutations, which raises disease thresholds for females and lowers their overall vulnerability.
Conversely, female-driven evolutionary factors—such as fluctuations in reproductive hormones linked to stress and social conditions—help explain why women face heightened risk for certain mental disorders, including major depressive disorder. The authors emphasize that bodies record evolutionary history and cells retain molecular memories of those histories.
Applying an evolutionary framework like the Sexual Selection–Sex Hormone theory provides historical context for how sex-biased diseases and mental disorders developed and offers a promising direction for new preventive measures and treatment strategies grounded in genomic and evolutionary evidence.