Some people have genetic variants in their genome that increase their reproductive success. As a result, they have more children on average, but at the same time have a shorter life expectancy than people without these gene mutations, as a study suggests. From an evolutionary perspective, this could be a genetic tug of war, the researchers report. Why these genes only allow a compromise and not both is only beginning to be researched. In addition, the discovery may not apply to all population groups.
In nature, gene mutations that are beneficial to those who carry them usually prevail. Gene variants that counteract the aging process in humans and increase our life expectancy represent such an advantage and should therefore theoretically be passed on from generation to generation in the long term to a greater extent than genes that have the opposite effect. But reality seems to refute this principle: As previous individual case studies have shown, we humans and animals pass on gene variants that cause us to age and reduce our life expectancy at an above-average rate. However, only if these mutations also mean that we have a lot of offspring at a young age.
Science calls this genetic tug-of-war over the simultaneous advantages and disadvantages of the same gene variants the “antagonistic pleiotropy hypothesis,” whereby the number of children appears to be more important than the age. From an evolutionary perspective, this could make sense because it promotes the transmission of one's own genes as widely as possible - and thus the evolutionary fitness of the species. However, whether the theory put forward in 1957 is actually correct is also controversial among experts because it has not yet been clearly proven. Because both aspects – having many children and a long life – are not contributed by just one gene, but by countless gene variants and environmental factors.
Genetic tug of war between life expectancy and fertility
To get closer to solving this puzzle, Erping Long from the Chinese Academy of Medical Sciences (CAMS) and Jianzhi Zhang from the University of Michigan have now carried out a comprehensive analysis for the first time and analyzed data from around 276,400 people from the British UK Biobank - one one of the largest biomedical data collections in the world. The two researchers compared the test subjects' gene sequences with the actual life expectancy, number of children and the age at first and last menstruation. They took into account 583 gene variants that are important for reproduction. From this they determined statistical key figures that make comparison easier.
It showed that men and women with higher values for genes that predispose them to successful reproduction also had a lower chance of living to the age of 76 or older. In addition, these gene variants increased in the study population between 1940 and 1969, as the researchers report. This suggests that the genes for better reproduction were actually passed down over the decades and prevailed through evolution, even though they were associated with a shorter life expectancy.
The connection is more complex
This could mean that Long and Zhang have confirmed the controversial theory of genetic tug-of-war. “Natural selection cares little about how long we live after reproduction is complete, since our biological fitness is largely determined by the end of reproduction,” Zhang explains. “Interestingly, we also found that the birth of two children is statistically associated with the longest lifespan,” Zhang continues. “If you have fewer or more children, your life expectancy is shortened.” This applied to both men and women. The result, which previous studies have already come to, suggests that the connection between age and the number of children is not linear, but rather more complex.
In addition, the two researchers also found initial evidence in the data about how these gene variants work in our bodies. Accordingly, some of the mutations that are beneficial for reproduction are also linked to skin and lung cancer, others to osteoarthritis or cardiovascular diseases. For many other variants, the mechanism by which they influence reproduction and aging remains unclear. However, a striking number of these gene variants have more than one function and regulate multiple tissues or other genes. In total, 123 of the 583 gene variants examined influenced not only reproduction, but also aging - about five times more than would be expected by pure chance, as Long and Zhang report.
Lifestyle plays a bigger role than genes
The results reflect the genes and lifestyle habits of the British population, but are not necessarily valid for other populations. Because reproductive success and lifespan are influenced by both genes and the environment. “One needs to be careful when extrapolating our results because other populations have different social and environmental factors as well as genetic backgrounds,” say Long and Zhang. Studies with data from other populations must therefore first show whether the findings are generally valid - and how relevant they are today. If you take into account that contraceptives and abortions have had a massive impact on reproduction in recent decades and that medical advances continue to increase lifespan, genes play a comparatively minor role today, say the researchers. Lifestyle and technical possibilities had a much greater impact.
Source: Erping Long (Chinese Academy of Medical Sciences) et al., Science Advances, doi: 10.1126/sciadv.adh4990