A unique gene influences growth, maturity, and lifespan in vertebrates

A gene named vgll3 plays a key role in regulating growth, sexual maturity, and longevity in vertebrates. A recent study conducted on the fish Nothobranchius furzeri, a species with a naturally short lifespan, revealed that this gene produces opposite effects depending on age. In males, a genetic modification of vgll3 accelerates growth and sexual maturation, while increasing cell division in various tissues, such as germ stem cells and intestinal cells. However, this early maturation comes with long-term costs: modified fish develop tumors resembling melanomas as they age and have a reduced life expectancy.

Researchers observed that vgll3 is primarily expressed in the somatic cells of male gonads, such as Sertoli and Leydig cells, suggesting a sex-specific role. By genetically manipulating two different forms of this gene, they found that males carrying mutations in exon 1 exhibited faster maturation, increased size, and greater weight compared to unmodified fish. These changes are explained by an increase in stem cell proliferation and a modification of the response to DNA damage.

To confirm the link between vgll3 and tumor development, scientists created an immunodeficient fish model by mutating the rag2 gene. This allowed the successful transplantation of cells derived from the expansions of melanocytes observed in aged fish carrying the vgll3 mutation. The transplanted cells formed invasive tumors, confirming their cancerous nature. Additionally, modified males showed an increased risk of age-related mortality, with a 15% reduction in their median lifespan.

This discovery illustrates an evolutionary mechanism called antagonistic pleiotropy, where a gene promotes beneficial traits early in life, such as rapid growth and early maturation, but leads to harmful effects later, such as increased cancer susceptibility and reduced longevity. This trade-off could explain why certain genes, even if they shorten lifespan, persist in natural populations. Indeed, in environments where early reproduction is essential for species survival, such as in the ephemeral habitats of the fish Nothobranchius furzeri, immediate benefits outweigh long-term costs.

In humans and other vertebrates, previous studies had already linked vgll3 to the age of sexual maturity, hormone levels, and even certain types of cancer. These new findings reinforce the idea that this gene acts as a major regulator of life history traits, balancing early benefits and late costs. The precise mechanisms by which vgll3 influences these processes remain partially unknown, but its role in regulating the cell cycle, DNA repair, and hormonal signaling pathways is beginning to be better understood.

Researchers also noted that vgll3 appears to have been subject to positive selection in annual fish species, suggesting that its role in accelerating maturation may have been favored by evolution in environments where survival depends on rapid reproduction. This could explain why variants of this gene are so widespread among vertebrates, despite their negative effects on longevity.

This study opens new perspectives for understanding how certain genes shape aging and age-related diseases. It highlights the importance of evolutionary trade-offs in the regulation of complex traits, where short-term benefits can justify long-term costs.

Attributions and Sources

Origin of the Study

DOI: https://doi.org/10.1038/s41467-026-72381-0

Title: An antagonistically pleiotropic gene regulates vertebrate growth, maturity, and lifespan

Journal: Nature Communications

Publisher: Springer Science and Business Media LLC

Authors: Eitan Moses; Marva Bergman; Tehila Atlan; Elizabeth M. L. Duxbury; Roman Franěk; Omer Ben Dor; Henrik von Chrzanowski; Enas R. Abu-Zhayia; Nabieh Ayoub; Shay Kinreich; Ido Ben-Ami; Alexei A. Maklakov; Itamar Harel