The penis may have more in common with other stubby projections--fingers and toes--than most of us might have guessed. Researchers have discovered that the same genes that direct a mammalian embryo to sprout digits also tell male embryos to make a penis. The findings, reported in today's Nature, suggest that the penis, fingers, and toes may have evolved under control of the same primordial genes.
The first clue that digits and penises might be birds of a feather came in 1991, when a team led by developmental biologist Denis Duboule of the University of Geneva and Pierre Chambon of the Institute for Genetics and Molecular and Cellular Biology in Strasbourg, France, found that some mice with a mutated gene, called hoxd13, had abnormally small digits and malformed penises. The gene belongs to a family of so-called HOX genes, which are active in controlling development of body segments and appendages in a wide range of organisms. Then last February, a team led by Jeffrey Innis of the University of Michigan, Ann Arbor, showed that people with a hereditary disease called "hand-foot-genital syndrome" have a mutation in a related human gene, HOXA13. This rare disease leads to short thumbs and big toes and sometimes a urethra shifted to the base of the penis.
Those findings prompted the two teams to work together to breed mice lacking four genes: three hoxd genes and a mouse version of hoxa-13, which together are known to direct the development of limb ends. The embryos survived long enough to have distinct anatomical defects, including missing lower limbs and digits--and the absence of the entire lower urinary tract and penis. This suggested to the team that digits and penises might have emerged from the innovative use of the same genes: HOX genes. "Perhaps the origin of the penis correlates to the introduction or improvement of the digits," says Duboule.
The finding "strengthens the genetic connection between genitalia and limbs and feet," says cell biologist Bjorn Olsen of Harvard Medical School in Boston. But others are skeptical about whether this genetic connection extends widely in the animal kingdom. Axel Meyer, an evolutionary biologist at the University of Konstanz in Germany, says that sharks, fish, and other aquatic creatures have penislike appendages that evolved from finlike structures that had nothing to do with limbs.