Ferocious female moles have hormones and genitals similar to men. We now know how this happens.

Moles live a hard life underground. As a result, they developed useful adaptations, such as excavator-like claws. Female moles in particular have developed an unusual strategy: high levels of testosterone, the male hormone.

This is an evolutionary advantage. It produces stronger muscles for digging, foraging and aggression, to help mothers defend themselves and their young.

Most of the year, female moles look and behave like males. They have masculinized genitals, with no external vagina and an enlarged clitoris. But when mating season comes, testosterone levels drop and a vagina forms; mating and birth follow.

How they do this has remained a mystery for a long time. But now, complete sequencing of the mole’s genome has revealed the genetic changes underlying this strange cycle in female moles, by which reproductive organs (gonads) develop and hormones are produced.

Gonads and hormones

Male development in humans and other mammals is determined by chromosomes (the structures within the cells of living things that contain genes). Females have two copies of an X chromosome. Males have a single X and a male-specific Y chromosome.

In XY embryos, a gene called SRY on the Y chromosome it intervenes in a network of 60 other genes. SRY it activates the genes of the testis and deactivates the genes of the ovary to transform a crest of cells into a testis.

In the testicle, one type of cell specializes to produce sperm and another (Leydig cells) produces male hormones, including testosterone.

Testosterone is responsible for the most visible sexual differences in males, such as larger bodies, more muscle mass, male genitalia, and more aggression. In XX embryos, an alternate path creates an ovary, which pumps estrogen.

So in mammals, different genetic pathways drive the same piece of embryonic tissue to become an ovary or a testicle. In general, there is no middle ground.

But female moles have a testicle patch inside the ovaries.

An act of evolutionary balance

In 1993, it was discovered that the basis of “intersex development” in female moles is a gonad with both ovarian and testicular tissue.

Like other male mammals, in males have a Y chromosome, which carries the SRY gene that directs the formation of the testis.

Also, like other mammals, female moles lack a Y chromosome. Curiously, however, instead of developing ovaries, they develop “ovotestes,” with ovarian tissue at one end and testicular tissue at the other.

Ovarian tissue lays eggs and enlarges during reproduction, then regresses. Testicular tissue is filled with Leydig cells that produce testosterone (but not sperm). Outside the breeding season, it expands to become larger than the ovarian tip.

This explains why female moles have male genitals and are muscular and aggressive. But how does a testicle patch form in female moles if they don’t have any SRY gene to activate the process?

Genetic modifications underlying the development of ovotestis

To look for genetic changes that could allow this to happen, a global consortium of scientists sequenced the entire genome of the mole.

They found no differences between moles and other mammals in the protein products of the 60 genes involved in sex determination. However, they discovered mutations that altered the file regulation of two of these genes in female moles.

A difference was found in the DNA sequences of a gene vital for the development of the testes: FGF9. In all mammals, this gene activates testicular growth in XY embryos and inhibits genes that determine ovarian development.

In females of other mammals, the FGF9 the gene is deactivated in the absence of SRY, but in female moles it remains on.

Genome sequencing revealed why: a large chunk of DNA just upstream of FGF9 is upside down in moles. This inversion removes the normal control sequences from the gene, allowing it to stay longer in XX embryos.

The other gene affected in female moles is CYP17A1, which codes for an enzyme essential for the production of androgens (male hormones). In female moles, this gene and its surroundings have two extra copies, which increase testosterone production.

To show that these genomic changes were indeed responsible for masculinizing female moles, the researchers introduced them into mice, causing sex reversal and higher testosterone levels.

It is important to note that these evolutionary changes are in regulation gene activity, rather than in the regulation of protein products, which could compromise other normal functions.

What it means for sex and evolution

Since mammals, including humans, develop as both males and females, we have been accustomed to considering the development of testes or ovaries in the embryo as rigorous alternatives, depending on an on / off switch (the presence or the absence of the Y chromosome e SRY gene).

But we now know that there is a complex genetic web full of checks and balances that is the basis for alternative paths of sexual development.

There are many studies on babies born with mutations in one of these genes. This indicates a more complex picture of the wiring behind the “switch” responsible for the variation in human sexual development.

There are also ferocious females in other mammal species. Female spotted hyenas are larger and more dominant than males and have male genitalia. We don’t know how this genetic change works.

The downside to this is that mating is complicated. Cubs are born through the female’s narrow phallus. Mothers and / or puppies often die during this intense process.

So while these larger, more aggressive females rule the hyena roost and get first choice at meals, like most things in the wild, it seems this comes at a price.

Large moles and ferocious female hyenas remind us that the natural world, as always, has unique evolutionary differences, illuminating our view of human variation.

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