Why don't humans have tails? Answer may lie in genetic mechanism

Humans have many wonderful qualities, but we lack something that is a common feature among most animals with backbones: a tail. Exactly why this occurs has been a mystery.

Tails are useful for balance, propulsion, communication and defense against biting insects . However, humans and our closest primate relatives – the great apes – said goodbye to tails about 25 million years ago, when the group split from the Old World monkeys. The loss has long been associated with our transition to bipedalism, but little was known about the genetic factors that triggered taillessness in primates.

Now, Scientists have traced our tail loss to a short sequence of genetic code that is abundant in our genome but had been discarded for decades as junk DNA. , a sequence that apparently serves no biological purpose. They identified the stretch, known as the Alu element, in the regulatory code for a gene associated with tail length called TBXT. Alu is also part of a class known as jumping genes, which are genetic sequences capable of changing their location in the genome and triggering or undoing mutations.

At some point in our distant past, the Alu AluY element jumped into the TBXT gene in the ancestor of hominoids (great apes and humans). When scientists compared the DNA of six hominoid species and 15 non-hominoid primates, they found AluY only in the hominoid genomes, the scientists reported Feb. 28 in Nature magazine. And in experiments with genetically modified mice – a process that took about four years – manipulating Alu insertions into the rodents' TBXT genes resulted in variable tail lengths.

Before this study, “there were many hypotheses about why hominoids evolved to be tailless,” the most common being connecting the absence of a tail to the upright posture and the evolution of bipedal gait said study lead author Bo Xia, a researcher at the Observatory of Gene Regulation and principal investigator at the Broad Institute of MIT and Harvard University.

But to pinpoint precisely how humans and great apes lost their tails, “nothing had been discovered or hypothesized before,” Xia told CNN by email. “Our discovery proposes a genetic mechanism for the first time,” he said .

And because tails are an extension of the spinal column, the findings could also have implications for understanding neural tube malformations that can occur during human fetal development, according to the study.

See what no one else has seen

A breakthrough moment for researchers came when Xia was reviewing the TBXT region of the genome in an online database widely used by developmental biologists, said study co-author Itai Yanai, a professor at the Institute of Systems Genetics and Molecular Biochemistry and Pharmacology. from New York University Grossman School of Medicine.

“It must have been something that thousands of other geneticists looked at,” Yanai told CNN . “That's amazing, isn't it? That everyone is looking at the same thing, and Bo noticed something that no one noticed.”

Alu elements are abundant in human DNA; the insertion in TBXT is “literally one in a million that we have in our genome,” Yanai said. But while most researchers had dismissed TBXT's Alu insertion as junk DNA, Xia noticed its proximity to a neighboring Alu element. He suspected that if the elements came together, they could trigger a disruptive process in the production of proteins in the TBXT gene.

“It happened in the blink of an eye. And then it took four years of working with mice to actually test it,” Yanai said.

In their experiments, the researchers used CRISPR gene editing technology to create mice with the insertion of Alu into their TBXT genes. They found that Alu caused the TBXT gene to produce two types of proteins. One led to shorter tails; the more of this protein the genes produced, the shorter the tails .

This discovery adds to a growing body of evidence that Alu elements and other jumping gene families may not be “junk” after all, Yanai said.

“While we understand how they replicate in the genome, we are now forced to think about how they are also shaping very important aspects of physiology, of morphology, of development,” he said. “I find it amazing that an Alu element – ​​a small, insignificant thing – can lead to the loss of an entire appendage like the tail.”

The efficiency and simplicity of Alu mechanisms for affecting gene function have been underestimated for too long, Xia added.

“The more I study the genome, the more I realize how little we know about it,” said Xia.

Humans still have tails when we are developing in the womb as embryos ; This small appendage is inherited from the tailed ancestor of all vertebrates and includes 10 to 12 vertebrae. It is only visible from the fifth to the sixth week of pregnancy and, by the fetus' eighth week, its tail usually disappears . Some babies retain an embryonic tail remnant, but this is extremely rare and such tails usually lack bone and cartilage and are not part of the spinal cord. reported another team of researchers in 2012.

But while the new study explains the “how” of tail loss in humans and great apes, the “why” is still an open question, said biological anthropologist Liza Shapiro, a professor in the anthropology department at the University of Texas at Austin.

“I think it's really interesting to pinpoint a genetic mechanism that may have been responsible for tail loss in hominoids, and this paper makes a valuable contribution in that regard,” Shapiro, who was not involved in the research, told CNN by email.

“However, if this was a mutation that randomly led to tail loss in our ape ancestors, the question still arises as to whether the mutation was maintained because it was functionally beneficial (an evolutionary adaptation), or simply was not a hindrance.” said Shapiro, who investigates how primates move and the role of the spine in primate locomotion.

By the time ancestral primates began walking on two legs, they had already lost their tails. The oldest members of the hominid lineage are the early Proconsul and Ekembo apes (found in Kenya and dated to 21 million and 18 million years ago, respectively). Fossils show that although these ancient primates lacked tails, they were tree dwellers who walked on four limbs with a horizontal body posture like apes, Shapiro said.

“So the tail was lost first, and then the locomotion that we associate with great apes evolved later,” Shapiro said. “But that doesn’t help us understand why the tail was lost in the first place.”

The idea that upright walking and tail loss were functionally linked, with tail muscles being repurposed as pelvic floor muscles, “is an old idea that is NOT consistent with the fossil record,” she added. .

“Evolution works from what is already there, so I wouldn't say that the loss of the tail helps us understand the evolution of human bipedalism in a direct way. This helps us understand our great ape ancestry,” she said.

Ancestral tail

For modern humans, tails are a distant genetic memory. But the story of our tails is far from over, and there is still a lot about tail loss for scientists to explore, Xia said.

Future research could investigate other consequences of the Alu element in TBXT, such as impacts on human embryonic development and behavior, he suggested. Although the absence of a tail is the most visible result of Alu insertion, it is possible that the presence of the gene also triggered other developmental changes—as well as changes in locomotion and related behaviors in early hominoids—to accommodate the loss of the tail.

Other genes likely also played a role in tail loss. Although Alu’s role “appears to be very important”, other genetic factors likely contributed to the permanent disappearance of the tails of our primate ancestors “, said Xia.

“It's reasonable to think that during this time, there were many other mutations related to stabilizing tail loss,” Yanai said. And because such evolutionary change is complex, our tails are gone forever, he added. Even if the driving mutation identified in the study could be undone, “it still wouldn’t bring back the tail.”

The new findings may also shed light on a type of neural tube defect in embryos known as spina bifida . In their experiments, the researchers found that when mice were genetically modified for tail loss, some developed neural tube deformities that resembled spina bifida in humans.

“Perhaps the reason we have this condition in humans is because of this commitment our ancestors made 25 million years ago to lose their tails,” Yanai said. “Now that we’ve made this connection to this particular genetic element and this particularly important gene, it could open doors in studying neurological defects.”

(Mindy Weisberger is a science writer and media producer whose work has appeared in Live Science, Scientific American, and How It Works magazine)