The genes you inherit from your mother and father may be locked in a hidden evolutionary battle inside your cells, with profound effects on your health, growth, and metabolism. A landmark study analyzing DNA from nearly 237,000 people has uncovered over 30 examples of this genetic conflict, where the same gene variant produces dramatically different sometimes completely opposite effects depending on which parent it came from.
"We found compelling evidence for an evolutionary phenomenon that's been theorized for decades but rarely observed at this scale," says Robin Hofmeister at the University of Lausanne in Switzerland, who led the research published in Nature. "Your maternal and paternal genes are essentially competing over resource allocation, and this competition shapes traits from your height to your risk of diabetes."
Scientists have long suspected that some genes behave differently depending on their parental origin, a phenomenon called parent-of-origin effects (POEs). According to evolutionary theory, this genetic conflict arises because fathers' genes benefit from offspring that extract maximum resources from mothers, promoting growth and energy consumption. Meanwhile, mothers' genes favor more conservative resource use, preserving the mother's health for future pregnancies.
But studying these effects has been challenging because it typically requires genetic data from both parents, which is rarely available in large-scale studies. Hofmeister's team developed an innovative workaround, using patterns of DNA sharing between relatives, along with sex chromosomes and mitochondrial DNA, to infer which genes came from which parent without needing parental genomes.
Applying this method to the UK Biobank, Estonian Biobank, and a Norwegian cohort, the researchers identified over 30 POEs affecting mainly traits linked to resource allocation, such as growth and metabolism. More than one third of these showed opposite parental influences.
One striking example involves a variant near genes called KLF14 and MEST at chromosome location 7q32.2. When inherited from the father, this variant decreased triglyceride levels, but when inherited from the mother, it increased them. The researchers believe this occurs because the variant affects different genes depending on its parent of origin, influencing the maternally expressed KLF14 when inherited from mother, but the paternally-expressed MEST when from father.
Even more dramatically, a variant at chromosome 11p15.5 showed a bipolar effect on type 2 diabetes risk. The paternal version increased diabetes risk by 14%, while the maternal version was protective, reducing risk by 9%. This locus had been identified over 15 years ago but never successfully replicated until now, highlighting the power of the new approach.
The effects of this genetic conflict begin early. When the team examined height and body mass index (BMI) measurements in over 42,000 Norwegian children from birth to age 8, they found that parent-of-origin effects present in infancy persisted into adulthood.
A variant affecting BMI showed a particularly intriguing pattern: when inherited from the mother, it increased BMI in infancy but decreased BMI and hip circumference in adulthood, with the effect gradually reversing over time.
"These findings suggest that parental genetic conflicts influence our entire developmental trajectory, not just single time points," notes Hofmeister.
The discovery validates 87% of the testable associations when replicated in independent cohorts, demonstrating the robustness of these effects. This hidden layer of genetic complexity could explain why some people respond differently to treatments or have varying disease risks despite carrying the same genetic variants.
"We've been missing half the story by not considering parent of origin," says Hofmeister. "For precision medicine to truly deliver on its promise, we need to know not just what genetic variants people carry, but which parent they came from."
The findings could be particularly relevant for metabolic conditions like diabetes and obesity, where multiple POEs converge on related biological pathways. As genetic testing becomes more sophisticated, incorporating parent-of-origin information could improve disease risk prediction and treatment selection.
This evolutionary battle in our genomes, fought between maternal and paternal genes over millions of years, continues to shape human health today, a reminder that our bodies are still influenced by ancient biological conflicts we're only beginning to understand.