2024-03-23 17:14:00
(CNN) – Humans have many wonderful qualities, but we lack something that is a common characteristic among most animals with backbones: a tail. The exact reason has been 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 tails about 25 million years ago, when the group split from the Old World monkeys. This loss has long been associated with our transition to bipedalism, but little was known about the genetic factors that caused taillessness in primates.
Now, scientists have discovered that the loss of the tail is due to a short sequence of genetic code that is abundant in our genome, but that for decades had been considered junk DNA, a sequence that apparently has no biological function. They identified the fragment, known as the Alu element, in the regulatory code of a tail length-associated gene 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 element AluY jumped 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 AluY only in the genomes of hominoids, they reported February 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 genes resulted in tails of variable length.
Before this study, “there were many hypotheses about why hominoids evolved without tails,” the most common of which linked the absence of a tail to upright posture and the evolution of bipedal gait, explains the study’s lead author, Bo Xia, a researcher at the Gene Regulation Observatory and principal investigator at the Broad Institute of MIT and Harvard University.
But as for identifying precisely how humans and great apes lost their tails, “there was (previously) nothing discovered or hypothesized,” Xia told CNN in an email. “Our discovery is the first time that a genetic mechanism has been proposed,” she added.
And since 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.
“One in a million”
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, according to Itai Yanai, a co-author of the study and a professor at the Institute of Systems Genetics and Biochemistry and Pharmacology. at New York University Grossman School of Medicine.
In the study, the genetically modified mice have tails of different lengths: from tailless to long tails. (Credit: Itai Yanai)
“It must have been something thousands of other geneticists looked at,” Yanai told CNN. “It’s amazing, right? 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 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 they paired, they could trigger a process that altered protein production in the TBXT gene.
“That happened in an instant. And then it took us four years to test it with mice,” explains Yanai.
In their experiments, the researchers used CRISPR gene editing technology to breed mice with the Alu insertion in their TBXT genes. They discovered that Alu caused the TBXT gene to produce two types of proteins. One of them led to shorter queues; The more of that 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.
“Although we know how they replicate in the genome, we are now forced to think about how they also shape very important aspects of physiology, morphology and development,” he said. “I think it’s amazing that one Alu element – one small thing – can lead to the loss of an entire appendage like the tail.”
The effectiveness and simplicity of Alu mechanisms in 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,” Xia said.
No glue and arboreal
Humans still have a tail when we develop in the womb as embryos; This small appendage comes from the tailed ancestor of all vertebrates and includes between 10 and 12 vertebrae. It is only visible between the fifth and sixth week of gestation, and by the eighth it usually has disappeared. Some babies retain an embryonic remnant of a tail, but this is extremely rare and such tails typically lack bone and cartilage and are not part of the spinal cord, another team of researchers reported in 2012.
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 Liza Shapiro, a professor in the department of anthropology at the University of Texas at Austin.
“I think it’s very interesting to point out a genetic mechanism that could 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. in an email.
In the study, the genetically modified mice have tails of different lengths: from tailless to long tails. (Credit: Itai Yanai)
“However, if this was a mutation that randomly led to the loss of the tail 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 was not a hindrance.” “said Shapiro, who researches how primates move and the role of the spine in primate locomotion.
When ancient primates began to walk on two legs, they had already lost their tails. The oldest members of the hominid lineage are the primitive apes Proconsul and Ekembo (found in Kenya and dated 21 and 18 million years ago, respectively). Fossils show that although these ancient primates lacked tails, they were arboreal, walking on four limbs with a horizontal body posture, like monkeys, Shapiro explains.
“So first the tail was lost and then the locomotion that we associate with living apes evolved,” he explains.
Two-legged walking may have evolved to adapt to the loss of the tail, which would have made it difficult for primates to balance on branches, “but it doesn’t help us understand why the tail was lost in the first place,” Shapiro said. . The idea that upright walking and tail loss were functionally linked, and that tail muscles were repurposed as pelvic floor muscles, “is an ancient idea that does NOT agree with the fossil record,” he added.
“Evolution works off of what already exists, 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 ancestry,” he said. .
A queue as old as time
For modern humans, the tail is a distant genetic memory. But the story of our tails is far from over, and scientists still have a lot to explore about tail loss, Xia says.
Other consequences of the Alu element in TBXT, such as its impact on human embryonic development and behavior, could be studied in the future, he suggested. Although the absence of a tail is the most visible result of the Alu insertion, it is possible that the presence of the gene also caused other developmental changes – as well as locomotion and other related behaviors in early hominoids – to adapt to the loss. tail
It is also likely that other genes played a role in the loss of the tail. Although Alu’s role “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 during that time there were many more mutations related to the stabilization of tail loss,” Yanai said. And since this evolutionary change is complex, our tails disappeared forever, she added. Even if the driver mutation identified in the study could be undone, “it still wouldn’t give us back our tail.”
The new findings could 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 to lose their tails, some developed neural tube deformities similar to spina bifida in humans.
“Perhaps the reason humans suffer from this disorder is because our ancestors lost their tails 25 million years ago,” says Yanai. “Now that we have made this connection with this particular genetic element and this particularly important gene, it could open doors in the study of 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.
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