Why Humans do not have Tail

Humans have many wonderful qualities, but we lack something that’s a common feature among most animals with backbones: a tail. Exactly why that is has been something of 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 farewell to tails about 25 million years ago, when the group split from Old World monkeys. The loss has long been associated with our transition to bipedalism, but little was known about the genetic factors that triggered primate taillessness.

Now, scientists have traced our tail loss to a short sequence of genetic code that is abundant in our genome but had been dismissed for decades as junk DNA, a sequence that seemingly serves no biological purpose. They identified the snippet, known as an Alu element, in the regulatory code of 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 switching their location in the genome and triggering or undoing mutations.At some point in our distant past, the Alu element AluY 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 hominoid genomes, the scientists reported February 28 in the journal Nature. And in experiments with genetically modified mice — a process that took roughly four years — tinkering with Alu insertions in the rodents’ TBXT genes resulted in variable tail lengths.

Prior to this study “there were many hypotheses about why hominoids evolved to be tailless,” the most common of which connected taillessness to upright posture and the evolution of bipedal walking, said lead study author Bo Xia, a research fellow in 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 to propose a genetic mechanism,” he said.

And because tails are an extension of the spine, the findings could also have implications for understanding malformations of the neural tube that can occur during human fetal development, according to the study.‘One out of a million’

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

“It must have been something that thousands of other geneticists looked at,” Yanai told CNN. “That’s incredible, right? That everybody is looking at the same thing, and Bo noticed something they all didn’t.”

Alu elements are abundant in human DNA; the insertion in TBXT is “literally one out of 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 up, it could trigger a process disrupting protein production in the TBXT gene.

“That happened in a flash. 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 breed mice with the Alu insertion in their TBXT genes. They found that Alu made the TBXT gene produce two kinds of proteins. One of those led to shorter tails; 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 families of jumping genes may not be “junk” after all, Yanai said.

“While we understand how they replicate in the genome, we now are forced to think about how they’re also shaping very important aspects of physiology, of morphology, of development,” he said. “I think it’s astounding that one Alu element — one small, little thing — can lead to the loss of a whole appendage like the tail.”

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

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