Researchers have identified a human genetic variant that affects the sex ratio of newborns. They also discovered that numerous undiscovered genetic variants related to sex ratios may be present in human populations.
Every year, the number of boys and girls born tends to be about the same.
However, within individual families, there are instances where some couples have multiple daughters without any sons, while others have only sons and no daughters, as noted by evolutionary geneticist Jianzhi Zhang from the University of Michigan. This has led some researchers to consider whether parental genetics could be the reason behind this uneven sex ratio.
Currently, Zhang and doctoral student Siliang Song from U-M have uncovered a human genetic variant that appears to influence the sex ratio of children. Furthermore, they believe that many hidden genetic variants affecting sex ratios may still exist within human populations. Their findings have been published in the *Proceedings of the Royal Society B: Biological Sciences*.
“For many years, scientists have been investigating a genetic foundation for sex ratios, yet no clear evidence for genetic variations that shift the human sex ratio from the typical 50:50 balance has been discovered,” stated Zhang, who is a professor of ecology and evolutionary biology.
Zhang explains that this absence of findings has led some experts to conclude that the human sex ratio may not be influenced by mutations.
“However, this idea seems unlikely, as nearly all human traits are subject to genetic variation and mutation,” he added. “Instead, we believe that the variation in sexual ratios is hard to detect due to the imprecise nature of measuring the sex ratio.”
Specifically, an individual generally has a very small number of children, which can result in significant inaccuracies when estimating the actual sex ratio of their offspring. For instance, if someone has just one child, the estimated sex ratio could either be zero (if the child is a girl) or one (if it’s a boy), even when the true ratio is 0.5.
To explore the genetic factors affecting sex ratios, the researchers recognized that they needed a larger sample size than what has been used in previous studies. They utilized the UK Biobank, which is a biomedical database including the genetic and phenotypic data of around 500,000 British participants.
Through analysis of this data, they discovered a specific nucleotide change known as rs144724107, linked to a 10% increase in the likelihood of having a daughter compared to a son. However, this variant is rare in the UK Biobank population, found in only about 0.5% of participants. This nucleotide change is situated near the ADAMTS14 gene, which is part of a gene family involved in sperm production and fertilization. The researchers caution that their findings need to be confirmed in additional samples.
Moreover, the team identified two additional genes, RLF and KIF20B, that could also have an influence on the sex ratio.
The study supports a theory in evolutionary biology called Fisher’s principle, named after British statistician Ronald Fisher. This principle suggests that natural selection tends to favor genetic variants that boost births of the less common gender — for example, if there are fewer males than females in a population, genetic variants that increase the birth rate of males will be favored, and the opposite is true as well. This mechanism generally maintains a balanced sex ratio in populations.
“For Fisher’s principle to hold true, there need to be mutations that affect the sex ratio,” Zhang explained. “The lack of identified genetic variations impacting the human sex ratio has led some scientists to doubt the relevance of Fisher’s principle to humans.”
“Our research indicates that human data do, in fact, align with Fisher’s principle, and the reason no genetic variants influencing sex ratios had previously been found is due to the inaccuracies in measuring a person’s offspring sex ratio.”
Although Zhang and Song concentrated on human sex ratios, their findings could have useful applications in the field of animal husbandry.
“In agriculture, one sex, typically females, tends to be significantly more valuable economically than the other. For instance, hens are prized for egg production and female cows for milk. Lower-value individuals, mostly males, are often culled shortly after birth,” Zhang noted. “Identifying genetic variants in farm animals that have effects similar to what was observed with the human rs144724107 could lead to substantial profits and improved animal welfare.”
The researchers’ next goal is to validate their findings across other populations, which poses a challenge due to the necessity for large sample sizes and the rarity of the genetic variant they identified.
This research received funding from the U.S. National Institutes of Health.
