On the trail of the code of tail loss

A special genetic element apparently causes us and other great apes to develop only a small tailbone instead of a tail. © libre de droit/iStock

A special trademark in sight: A study now sheds light on the genetic basis of the lack of a tail in humans and their closest relatives. According to this, a special insertion in a “tail gene” leads to a lack of development in great apes. By transferring this genetic concept, the team was also able to suppress the formation of tails in mice. There were also indications that the evolution of tail loss may have been linked to the increased risk of certain embryonic development disorders in humans.

Most animals have something at the back - there are many shapes of tails that can have different functions. Most primates also have a long extension of the spine. But this is not the case with one particular group: the great apes, which include us along with chimpanzees, gorillas and orangutans, do not have a tail. Instead, during embryonic development, only the small coccyx develops. The loss of the tail is thought to have occurred in a common ancestor of great apes that lived about 25 million years ago. What exactly underpinned this development is unclear. It is possible that the absence of the tail was advantageous for a specific way of life or locomotion. However, the appendages could also have fallen victim to saving resources: sometimes characteristics disappear in the course of evolution simply because they are no longer useful.

What prevents tail growth?

The focus of the study by Bo Xia from the NYU Grossman School of Medicine in New York was not the purpose of the loss, but rather its genetic mechanism. “Our study was dedicated to explaining how evolution removed the tails,” said Xia. To address this question, the research team analyzed numerous vertebrate genes that show evidence of a connection to the development of tails. Ultimately, a gene called TBXT came into focus. Certain mutations in the coding region of this genetic makeup are known to lead to tail development disorders in animals.

But interestingly, the researchers discovered that great apes have a TBXT gene that differs in a special way from the genetic makeup of animals with tails. Accordingly, it contains an element of around 300 base pairs that is not part of the blueprint of the protein product of the gene. It turned out that this so-called Alu element occurs a second time at another location in the TBXT gene area - but in the reverse sequence direction. After this discovery, the researchers investigated the way in which these non-coding elements could influence the function of the genetic makeup.

As the team's experiments initially revealed, the constellation of the two elements indirectly influences the genetic product. As part of the processing of the genetic information, the two sequence sections can come together. This creates a loop that influences the reading process of the genetic code. Ultimately, this creates an alternative short form of messenger RNA, which leads to the production of a special TBXT gene product. Since the loop does not necessarily have to form, the “normal” protein also still forms. In other words, two versions of TBXT arise in humans and great apes, which may be associated with the lack of tail development.

Tailless mice prove the effect

In order to prove this effect experimentally, the researchers then carried out experiments with mice: using genetic methods, they created lines of rodents that have different versions of the TBXT gene system. This showed that with artificially created characteristics that correspond to those of great apes, the mice no longer developed tails that were shortened or no longer developed at all during embryonic development. This confirmed that the formation of the two isoforms of the TBXT gene product actually affects tail development. The results therefore suggest that this genetic change occurred in our distant ancestors. The resulting loss of the tail apparently proved beneficial and the system has become established in all representatives of the great apes to this day.

Interestingly, the team also came across an indication that this adaptation might have come at a certain price: in the mice that were equipped with the genetic tail loss concept, the researchers found defects in the development of the neural tube comparatively frequently during embryonic development. Such disorders are known to cause spina bifida in humans - a developmental disorder in which the spine is not formed correctly in the womb. “Future experiments could clarify to what extent the loss of the tail required an evolutionary trade-off that resulted in an effect that now affects about one in a thousand human newborns,” says senior author Itai Yanai of the NYU Grossman School of Medicine.

Source: NYU Langone Health / NYU Grossman School of Medicine, specialist article: Nature, doi: 10.1038/s41586-024-07095-8

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