Why don’t humans have tails?

(CNN) – Humans have many amazing traits, but we lack one thing that is a common feature among most vertebrates: a tail. The exact cause remains a mystery.

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

Now, scientists have discovered that the loss of the tail is caused by a short sequence of genetic code that is abundant in our genome, but for decades it was considered junk DNA, a sequence that apparently has no biological function. Not there. They identified a fragment in the regulatory code of a tail length-related gene called TBXT, known as an Alu element. Alu is also part of a class known as jumping genes, which are genetic sequences that are capable of changing their location in the genome and triggering or undoing a mutation.

At some time in our distant past, the Alu element Alu made the jump to the Tbxt gene in the ancestor of hominoids (great apes and humans). When scientists compared the DNA of six species of hominoids and 15 non-hominoid primates, they found AluVa only in the genomes of hominoids, they reported Feb. 28 in the journal Nature. And in experiments with genetically modified mice – a process that took about four years – modifying Alu insertions in the rodents’ TBXT gene resulted in tails of different lengths.

Before this study, “there were several hypotheses about why hominoids evolved without a tail,” the most common of which linked the absence of a tail to the evolution of upright posture and bipedal gait, said the study’s lead author, Bo. Zia, a researcher explains. Gene Regulation Observatory and principal investigator at the Broad Institute of MIT and Harvard University.

But as far as identifying exactly how humans and great apes lost their tails, “nothing had been discovered or hypothesized (before),” Xia told CNN in an email. “Our discovery is the first time that a genetic mechanism has been proposed,” he said.

And since the tail is an extension of the spinal column, the findings may also have implications for understanding neural tube malformations that can occur during human embryonic development, according to the study.

“One in lakhs”

A turning point for the 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 in the Institute of Systems Genetics and Biochemistry and Pharmacology. According to. At New York University Grossman School of Medicine.

In the study, genetically modified mice had tails of varying lengths: from no tails to long tails.  (Credit: Itai Yanai)

In the study, genetically modified mice had tails of varying lengths: from no tails to long tails. (Credit: Itai Yanai)

“This would have been something that thousands of other geneticists would have looked at,” Yanai told CNN. “It’s amazing, isn’t it? That everyone is looking at the same thing and Bo has realized something that they all haven’t.”

Alu elements are abundant in human DNA; The insertion in TBXT is “literally one of millions that exist in our genome,” Yanai said. But while most researchers had dismissed TBXT’s Alu insertion as junk DNA, Xia noticed its proximity to the neighboring Alu element. They suspected that if they paired, they might trigger a process that alters protein production in the Tbxt gene.

“It happened in an instant. And then it took us four years to test it on mice,” explains Yanai.

In their experiments, the researchers used CRISPR gene editing technology to breed mice with Alu insertions in their Tbxt gene. They found that Alu induced the Tbxt gene to produce two types of proteins. One of them caused the queues to become shorter; The more protein the genes produce, the shorter the tail.

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

“Although we know how they replicate in the genome, we are now forced to think about how they shape very important aspects of physiology, morphology and development,” he said. “I think it’s amazing that one Alu element – ​​one small thing – can cause the loss of an entire appendage like a tail.”

The effectiveness and simplicity of the Alu mechanism in influencing gene function has been underestimated for too long, Xia said.

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

Tailless and Arboreal

Humans have a tail even when we develop as fetuses in the womb; This small appendage comes from the tailed ancestor of all vertebrates and consists of 10 to 12 vertebrae. It appears between the fifth and sixth weeks of pregnancy and usually disappears by the eighth week. Another team of researchers reported in 2012 that some babies retain embryonic remains of the tail, but this is extremely rare and such tails usually lack bone and cartilage and are not part of the spinal cord. Are.

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

“I think it’s very interesting to pinpoint a genetic mechanism that may account for the loss of the tail in hominoids, and this paper makes a valuable contribution in that regard,” Shapiro, who was not involved in the research, said. Told CNN. E-mail.

In the study, genetically modified mice had tails of varying lengths: from no tails to long tails.  (Credit: Itai Yanai)

In the study, genetically modified mice had tails of varying lengths: from no tails to long tails. (Credit: Itai Yanai)

“However, if it was a mutation that caused tail loss randomly in our ape ancestors, it still raises the question of whether the mutation was maintained because it was functionally beneficial (an evolutionary adaptation), Or simply wasn’t an obstacle.” ” said Shapiro, who researches how primates walk and the role of the spine in primate locomotion.

When ancient primates began walking on two legs, they had already lost their tails. The oldest members of the hominid lineage are the primitive apes Proconsul and Akembo (found in kenya and dated to 21 and 18 million years ago, respectively). Shapiro explains that the fossils show that although these ancient primates lacked a tail, they were still arboreal, and walked on four limbs with a horizontal body posture like monkeys.

“So the tail was lost first and then the locomotion that we associate with living apes evolved,” he explains.

Walking on two legs may have evolved to adapt to the loss of the tail, which would have made it more difficult for primates to balance on branches, “but that doesn’t help us understand why the tail was lost in the first place,” says Shapiro. Said. , The idea that upright walking and the loss of the tail were functionally linked, and that tail muscles were reused as pelvic floor muscles, “is an ancient idea that does not agree with the fossil record,” he said. Said.

He said, “Evolution works from what already existed, so I wouldn’t say that the loss of the tail helps us understand the evolution of human bipedalism in any direct way. However, it does help us understand our ape lineage.” “Helps.”

a line as old as time

For modern humans, the tail is a distant genetic memory. But the story of our tails is not over yet, and scientists still have a lot to discover about tail loss, Xia says.

They suggested that other consequences of the Alu element in TBXT, such as its effect on human fetal development and behavior, could be studied in the future. Although the absence of the tail is the most visible consequence of the Alu insertion, it is possible that the presence of the gene also adapted to the loss along with other developmental changes in locomotion and other related behaviors in early hominoids.

It is also likely that other genes may have played a role in the loss of the tail. Although the role of Alu “seems very important,” it is likely that other genetic factors contributed to the permanent disappearance of the tail in our primate ancestors, Xia says.

“It is reasonable to think that there were many more mutations related to stabilization of tail loss during that time,” Yanai said. And because this evolutionary change was complex, our tails disappeared forever, he added. Even if the driver mutations identified in the study could be undone, “it still won’t give us our tails back.”

The new findings may also shed light on a type of neural tube defect in fetuses called spina bifida. In their experiments, the researchers found that when mice were genetically modified to lose their tails, some developed neural tube malformations similar to spina bifida in humans.

“Maybe the reason humans suffer from this disorder is that our ancestors lost their tails 25 million years ago,” says Yanai. “Now that we’ve made this connection with this particular genetic element and this particularly important gene, it can open the door to studying neurological defects.”

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

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