The presence of a transposable element might explain how humans and our great ape cousins lost our tails about 25 million years ago.
The mutation, discovered by NYU Langone Health graduate student Bo Xia, is in a gene called TBXT, which codes for a transcription factor involved in embryonic development—although, according to The New York Times, this wasn’t the first time TBXT has been implicated in mammalian tail morphology. As far back as 1923, Russian geneticist Nadezhda Dobrovolskaya-Zavadskaya exposed male mice to X-rays and then observed their progeny after they bred. She saw that some of their offspring developed shortened or kinked tails, and later experiments showed that these mice had TBXT mutations.
Still, this gene hadn’t specifically been linked to the lack of tails in apes until Xia and colleagues compared the sequences of TBXT from tailless apes to those of other primates with tails, analyses that were reported in a bioRxiv preprint last week and have not yet been peer reviewed. According to Science, they discovered the insertion of a 300–base pair Alu element in a noncoding region of all of the apes’ TBXT genes but none of the monkeys’. Alu elements—a kind of transposable element or “jumping gene” that can move around the genome—are common in human genomes, making up about 10 percent of our DNA.
“It wouldn’t have jumped out at me as an obvious mutation to test [for],” Harvard University evolutionary biologist Hopi Hoekstra tells Science, calling the insight “clever.”
The Alu appears to work in concert with another Alu that had previously jumped into the gene, Science reports. This second Alu was found in all of the primates studied, including the ones with tails. But when both were present, they could stick together to form a loop, resulting in a shorter mRNA transcript.
Humans and apes produce both longer and shorter versions of the transcript, but mice only make the longer version. When the researchers used CRISPR to introduce the two-Alu version of TXBT into mice, they found that having both copies of the mutant gene was lethal, but having a longer copy and a shorter copy resulted in a range of tail lengths, including no tail at all.
While this discovery sheds light on how apes lost their tails, why they did is another question entirely. “That’s the next outstanding question: What on earth would the advantage be?” Stony Brook University in New York evolutionary morphologist Gabrielle Russo tells the Times.
Additionally, the team found that of the mice genetically modified to have alterations in TBXT, many of them developed neural tube problems similar to the types of birth defects that cause spina bifida or anencephaly, although Hoekstra notes it’s unclear how the mouse and human phenotypes are related.
“We apparently paid a cost for the loss of the tail, and we still feel the echoes,” lead author and NYU Langone Health developmental geneticist Itai Yanai tells Science. “We must have had a clear benefit for losing the tail, whether it was improved locomotion or something else.”