The human sex ratio at birth is nearly 0.5, meaning about half of newborns are male. Fisher’s principle, which suggests that mutations affecting the sex ratio should exist, often explains this balance.
However, previous studies on humans have shown mixed results about whether such mutations influence the sex ratio. This raises the possibility that the nearly equal ratio could simply result from the random way X and Y chromosomes are distributed during sperm formation in males.
Zhang and U-M doctoral student Siliang Song have identified a human genetic variant that affects the sex ratio of children. They also discovered that many other hidden genetic variants likely influence the sex ratio in human populations.
Zhang said, “We think genetic variation of sex ratio is too difficult to detect because sex ratio is not measured precisely.”
Conflicts between males and females could replace the evolution of new species
Each person usually has only a few children, which can lead to significant errors in estimating the true sex ratio of their children. For instance, if someone has just one child, the estimated sex ratio would be either 0 (for a girl) or 1 (for a boy), even if the overall sex ratio is 0.5.
To study the genetic influence on sex ratio, the researchers needed a much larger sample than previous studies provided. They accessed the UK Biobank, which has genetic and health data from about 500,000 British participants.
This analysis identified a genetic change called rs144724107, linked to a 10% higher chance of having a girl than a boy. However, this change is rare, found in only about 0.5% of the participants. It is located near the ADAMTS14 gene, which is involved in sperm production and fertilization. The researchers also noted that their findings need further confirmation in other samples.
The researchers also found two additional genes, RLF, and KIF20B, that might influence the sex ratio.
These findings support a theory in evolutionary biology known as Fisher’s principle, named after British statistician Ronald Fisher. This principle suggests that natural selection favors genetic variants that increase the birth rates of the rarer sex. So, if there are fewer males than females, natural selection will promote mutations that lead to more males being born, and vice versa. This process helps maintain a roughly even sex ratio in the population.
Zhang noted that for Fisher’s principle to be valid, mutations must affect the sex ratio. The lack of previously identified genetic variations related to the human sex ratio has led some scientists to question whether Fisher’s principle applies to humans.
Zhang said, “Our study shows that human data are consistent with Fisher’s principle, and the reason no genetic variants of sex ratio had been discovered was the imprecision of the measure of a person’s offspring sex ratio.”
The authors said, “Although they focused on human sex ratio, their findings have practical applications in animal husbandry.”
Zhang said, “In agriculture, one sex—mostly females—often has substantially larger economic value than the other. For example, hens are valued for egg production and female cows for milk production.”
“Individuals of lower economic value, mostly males, are usually killed soon after birth. Finding genetic variants in farm animals with effects as large as that computed for humans rs144724107 would likely bring huge profits and contribute to animal welfare.”
Scientists are now looking forward to verifying their findings in other samples-not an easy task because of the large sample size requirement and the rareness of the identified genetic variant.
Journal Reference:
- Siliang Song and Jianzhi Zhang. In search of the genetic variants of human sex ratio at birth: was Fisher wrong about sex ratio evolution? Proceedings of the Royal Society B: Biological Sciences (2024). DOI: 10.1098/rspb.2024.1876
