Scientists Discover Genetic Mechanisms That Lead to Five-fingered Hands

A team of researchers has solved the mystery of how humans evolved to have five fingers. Early tetrapods had six fingers and how this changed during evolution was unknown. The new findings were just published in the journal Nature.

As early tetrapod animals made the transition from water to land, fins were evolving into fingers. Scientists know that there are two genes, Hoxa13 and Hoxd13, which play roles both in fin ray development and finger development. Palaeontological research shows that early tetrapods had six or more digits, raising the question of why humans and many other animals have just five.

Researchers from the Institut de recherches cliniques de Montréal (IRCM) and the Université de Montréal sought to find out how tetrapods began to develop just five digits. They speculated that two more genes, hoxa11 and hoxa13, were involved. During digit development in pentadactyl (five-fingered) animals, the genes activate in separate domains. In fish, however, the genes express in overlapped domains. An enhancer for the mouse Hoxa11 gene is also completely absent in zebrafish. All of these genes belong to the homeobox family, a set of genes that control embryonic development.

The research team triggered zebrafish-like gene regulation and expression in mouse embryos. The mice developed six or seven digits. This shows that new genes weren’t involved in the switch to pentadactyly. Instead, existing genes were repurposed and regulated differently in order to drive morphological changes in the digits. The findings suggest that the evolution of regulation mechanisms for the Hoxa11 gene was the major driver in the transition to five digits.

The team believes that their discovery may help scientists better understand certain types of developmental disorders. Many issues with fetal development are likely caused by issues with gene regulation and not simply mutations in the homeobox genes. The study also provides new insights into the early evolution of tetrapod animals.


Kherdjemil et al. Evolution of Hoxa11 regulation in vertebrates is linked to the pentadactyl state. Nature (2016).

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