Summary: Individuals carrying recessive gene mutations—previously believed to be unaffected—might actually encounter subtle disadvantages. This includes a range of medical issues, shorter educational achievements, and lowered reproductive success. A study involving over 300,000 people demonstrates that those with recessive genes linked to intellectual disability are particularly at risk, despite only having one defective gene copy.
This group was observed to be more often childless and had less education, indicating that evolutionary selection still applies to these seemingly dormant genes. These results question established theories and provide fresh perspectives on how natural and sexual selection could be influencing the human genome.
Key Facts:
- Hidden Impact: Carriers of recessive disease genes show a higher incidence of medical diagnoses and exhibit slightly lower reproductive success.
- Education Effect: Those with genes for intellectual disabilities tend to have shorter schooling.
- Sexual Selection: The decreased reproductive success may stem from subtle influences that affect mate selection and social situations.
Source: Radboud University
Generally, people who carry recessive disorders tend to be somewhat less healthy and have a decreased likelihood of having children.
Specifically, those with a recessive gene for intellectual disability reflect these disadvantages through reduced educational duration and increased childlessness, as seen in research from Radboudumc published in Nature Human Behavior.
Is it time to rethink what’s in our textbooks?
Dominant mutation
In a noteworthy 2014 study published in Nature, researchers from Radboudumc’s Department of Human Genetics uncovered something quite surprising.
Contrary to what was expected, inherited gene variations seldom caused intellectual disability.
More often, spontaneous mutations—mutations unique to the child and not present in either parent—account for these disabilities. Each child typically carries about a hundred such spontaneous mutations, with only one of these likely affecting a gene. And only a small number relate to intellectual disabilities. Nevertheless, these rare occurrences can and do happen.
From dominant to recessive
“We sensed there was more to the story,” noted Christian Gilissen, a professor of Genome Bioinformatics and the lead author of the 2014 publication.
“Children usually inherit a gene from both parents. If a single mutation leads to an intellectual disability, it’s classified as a mutation in a dominant gene.
“But other mutations impact recessive genes. A mutation in a recessive gene typically doesn’t affect the carrier unless both copies are mutated.
“In our practice, we rarely found double mutations in recessive genes among children with intellectual disabilities. This was puzzling since there are more recessive genes than dominant ones. It made us wonder where all the recessive mutations had gone.”
More medical diagnoses
This curiosity led to an extensive investigation, the findings of which were recently published in Nature Human Behavior.
“We first looked at how prevalent these recessive mutations are in the population,” explained Han Brunner, professor of clinical genetics, who collaborated on both publications.
Data from over 300,000 individuals in the UK Biobank were analyzed.
“Each person, on average, carries about two mutations across roughly 1,900 recessive genes. Textbooks say carriers of these recessive genes shouldn’t face disadvantages.
“But our study revealed that, as a group, they actually have more health issues and slightly fewer children. Thus, their chances of passing on genes linked to recessive disorders are lower.”
Less education
The genes for intellectual disabilities stood out as particularly rare among recessive genes. Evidently, another factor is in play, as shown by the UK Biobank data.
Gilissen stated, “Carriers of a recessive gene for intellectual disability are less likely to complete school. This indicates a lower level of education, which is unexpected because, according to current theory, they shouldn’t be affected by their recessive gene.”
More likely to be childless
Overall, those carrying recessive genes for intellectual disabilities tend to have fewer reproductive successes and shorter educational paths.
Brunner remarked, “In 1859, Darwin published On the Origin of Species by Means of Natural Selection, focusing on survival traits, health, and natural selection.
“Twelve years later, he refined his theory in The Descent of Man, and Selection in Relation to Sex. The idea is simple: having good genes isn’t enough if no one wants to mate with you.
“This touches on sexual selection. While we can’t definitively prove it yet, I speculate that sexual selection is likely a key factor behind these observations.”
Revisiting textbooks
The findings indicate that carriers of recessive disorders face a group-level selection disadvantage. Though past studies have pointed this out for specific disorders, this is the first instance demonstrating the phenomenon for recessive disorders collectively. That certainly warrants a place in academic literature.
Brunner concluded, “Our research suggests that genetic changes are ongoing, and evolution is far from stagnant. The idea that modern healthcare has halted evolution is a misconception.”
Gilissen added, “We will never be perfectly adapted for the challenges of the future.”
