Female moles have reproductive organs unlike any other mammal. If measured by the standards of other species, there are no fully female moles. Instead, there are males and individuals that would be considered intersex if they were another animal, having both ovarian and testicular tissue as well as vaginas that disappear between breeding seasons. A new study has explained the genetics underlying this unusual situation.
Sexual determination in every animal is much more complex than most of us were taught in high school biology. Up to 1 percent of the human population is intersex, having sexual anatomy differing from the typical male or female. Other animals are similar. Some reptiles and fish go even further, but most mammals stick closer to the binary.
Moles are the exception. In at least eight species, most males have XY sex chromosomes and produce only testicular tissue like other mammals. Functionally, female moles have two X chromosomes but possess “ovotestes”, a mix of ovaries and testes. The testicular component contains Leydig cells that produce androgens (“male” hormones), giving many of the females as much testosterone as the males, sometimes more. Biologists have concluded this is useful for a creature whose survival depends on its strength for digging but have lacked a genetic explanation to match the evolutionary one.
An analysis in Science of the genome of the Iberian mole (Talpa occidentalis, no relation to naked mole-rats) provides some answers.
"We hypothesized that in moles, there are not only changes in the genes themselves, but particularly in the regulatory regions belonging to these genes," said Professor Stefan Mundlos, from the Max Planck Institute for Molecular Genetics, in a statement.
The team's findings support this. The CYP17A1 gene, responsible for male hormones in many species, appears three times in the mole genome instead of just once, but that’s not the whole story. Certain sections of DNA occur in different locations in the mole genome compared to other mammals, changing the circumstances and extent of their expression.
"Our findings are a good example of how important the three-dimensional organization of the genome is for evolution," said senior author Dr Dario Lupiáñez. "Nature makes use of the existing toolbox of developmental genes and merely rearranges them to create a characteristic such as intersexuality. In the process, other organ systems and development are not affected."
To confirm they had identified the genetic causes, the team produced transgenic mice altered to match the moles. The male mice were unaffected, but the females produced as much testosterone as the males and were physically much stronger than unaltered female mice.
The work was particularly challenging for the large team because Iberian moles have not been successfully raised in the laboratory, so all work had to be done on wild moles.
The findings provide two important lessons with implications far wider than just moles. The paper notes that the work “highlights the evolutionary importance of genomic rearrangements and their potential to modulate developmental gene expression.”
The results could improve our understanding of intersex characteristics in humans. Mundlos noted it also refutes the tendency to treat intersex as a pathological condition, a historical hangover biologists and doctors are slowly starting to reject.