African clawed frog gene duplication created a master sex switch

A gene duplicated during the evolutionary past has been identified as the master switch deciding whether African clawed frog embryos become male or female.

The discovery shows how evolution can reallocate its most sensitive biological choices while keeping reproduction intact.

Gene controls frog sex

The African clawed frog (Xenopus laevis) is a wholly aquatic amphibian, recognised for its flattened body, strong legs and longstanding use as a laboratory model.

In this species, early development depends on a gene known as dm-w: when it is present, the entire sexual-development pathway is redirected towards female development.

Evolutionary geneticist Ben Evans traced the origins of this switch through work on established frog lines at McMaster University and the Marine Biological Laboratory (MBL).

On a human timescale, the change is remote, but it happened about 20 million years ago - a recent event for such a basic shift in vertebrate development.

The findings indicate that an older gene involved in sex regulation split into distinct male and female functions, allowing one copy to become nonessential and eventually assume control of sex determination.

This transfer was a turning point at which a stable reproductive system shifted into a different arrangement, laying the groundwork for the wider genetic account.

Female gene blocks males

In these frogs, dm-w occurs only in females and directs early reproductive organs towards becoming ovaries by suppressing male developmental pathways.

When female embryos lacked dm-w, they developed as males, leading the researchers to regard it as the most definitive genetic indicator of sex.

The central question was how an ordinary gene shared by both sexes had transformed into a female-specific switch.

To answer it, researchers had to trace the gene’s history to before dm-w arose, when frogs possessed a different set of genetic material.

Genome accidentally duplicated

Around 20 million years ago, an ancestor of Xenopus laevis acquired a doubled genome, copying the majority of its genes.

This event produced two functional versions of almost every gene, enabling one copy to alter while the other retained its original job.

Across subsequent generations, certain surplus copies disappeared, whereas others continued to develop new activity patterns in different tissues.

These differing outcomes created the conditions for sex-related genes to separate in function, since reproductive errors carry greater consequences than most other traits.

Gene copies diverged differently

Following genome duplication, the frog had two versions of the same sex-associated gene, each descended from a shared ancestor.

Disabling the copies individually uncovered an unequal result, although this only became apparent once the frogs reached adulthood.

Some females looked healthy externally, yet no eggs formed inside their bodies; fat occupied the space instead.

“Normally, when you open up a female, you see eggs everywhere,” noted Evans.

A gene copy for healthy sperm

The outcome in males differed, as the same gene copy proved necessary for producing healthy sperm.

Males of a closely related frog species stayed fertile when the gene was absent, but fertility failed in Xenopus laevis after that copy was removed.

Typical males generated far more sperm, whereas the few sperm remaining in mutants were both limited in number and abnormally shaped.

Evolution had, without obvious external changes to sex, reassigned an essential male role to this gene.

Females lost gene dependency

Female frogs showed a surprising division: egg production relied on just one of the two gene copies.

In the more ancestral-like species, deleting the gene stopped egg production altogether; female Xenopus laevis, however, could do without one copy.

This suggests that one version retained the original egg-producing function, while the other progressively ceased to be required.

After a gene copy no longer posed a risk to fertility, changing it was no longer hazardous.

Spare copy evolved freely

Once reproduction was protected, the redundant copy had scope to drift, adapt and acquire new behaviour.

Eventually, a section of this spare copy duplicated once more and developed into dm-w, the gene that now governs sex itself.

“By becoming nonessential, a copy of this gene was able to hijack the entire system,” Evans said.

These takeovers can succeed only if their timing remains exact, since sex must be determined early without interfering with later development.

Small changes flip development

This sort of takeover represented a genetic tipping point: a threshold at which a minor alteration changes developmental outcomes.

Sex determination relies on gene networks, where timing and dosage are crucial, and the dominant signal commits development to an ovary or testis.

Minor shifts in the point at which a gene activates, or in the strength of its activation, can drive the network beyond that threshold.

This sensitivity helps account for the rapid evolution of sex systems, while also showing why evolution seldom proceeds through blind experimentation.

Relevance to human fertility

In humans, the same gene contributes to keeping the testes working correctly, and disruptions may impair fertility long after development has finished.

The frog findings demonstrate that the gene can act very differently according to where and when it operates in the body.

Such adaptability helps explain why some fertility genes seem stable over long evolutionary periods before abruptly gaining different functions.

Human biology is not frog biology, but this work illustrates why examining males and females separately can uncover effects that might otherwise remain unseen.

The findings link a new sex switch with gene duplication, revealing how one copy shed its constraints while another acquired fresh responsibilities.

Investigating comparable changes in other frogs could show when these tipping points emerge and when evolution instead avoids them.