How we lost our tails
The tail of man's ancestors disappeared very quickly
Alexander Sokolov, XX2 century
Let's talk about the losses that our ancestors suffered in heavy evolutionary battles. One of such irreparable losses is the tail. Many primates can boast a gorgeous tail. In spider monkeys from the New World, the tail is actually the fifth limb, it clings to the branch perfectly, and even allows you to hold objects. The great apes here shyly looked down – there is, frankly, nothing to brag about. Probably, about 25 million years ago, the common ancestor of modern hominoids lost its tail, leaving behind only a pathetic coccyx of 3-4 fused vertebrae. Before that, for half a billion years, chordates walked around with tails, and now – bang! – he's not here. We can only wonder why this happened. Did the tail become unnecessary when the monkeys increased in size? Was it a hindrance in the transition to a terrestrial lifestyle? (We look at gibbon and doubt ...) Recent research by geneticists has shed some light on the genetics of the tail, which was helped by the study of tailless mutant mice. Scientists have obtained a list of 31 genes that play a role in the formation of tails in mammals. Nevertheless, it remained unclear exactly what genetic changes led to the disappearance of such a noticeable part of the body in the anthropoids.
To clarify the picture, the authors of the new study compared 31 "tailed" genes of humans and other primates. In addition to humans, orthologous genes (that is, genes of common origin with similar functions) of five great apes - humans, chimpanzees, bonobos, gorillas, orangutans, gibbons – and fifteen of their tailed relatives were analyzed.
By the way, Carl Zimmer in an article about this study for the New York Times writes that the researchers compared DNA of six tailless monkeys and nine tailed monkeys. And open the original article? And count? A great scientific journalist has no time?
First, the coding sequences were compared – that is, the part of DNA that is responsible for the amino acid composition of proteins – but nothing suspicious was found. Then the researchers took up the search for specific differences in hominids in non-coding DNA regions. And then luck was waiting for them: they found a piece of the genetic sequence of about 300 nucleotides in the sixth intron of the TBXT gene, present only in hominids.
An intron is a section of DNA that is cut out during gene transcription, i.e. it does not participate in protein coding.
The sequence found belonged to Alu repeats, a class of repetitive short DNA sequences that are very common in primate genomes. Humans have about 1 million copies of the Alu repeat, which is almost 10% of the entire genome. So it was exactly such an Alu repeat that was once embedded in the TBXT gene of the common ancestor of hominids. Moreover, the insert belongs to the AluY subfamily, the beginning of the activity of which, as geneticists believe, just about coincides with the time when our ancestors lost their tail.
The TBXT gene itself is very interesting, it was discovered almost 100 years ago by a Russian geneticist Nadezhda Dobrovolskaya-Zavadskaya. She investigated hereditary changes in mice under the influence of ionizing radiation and in 1923 received mutant mice with curved or shortened tails. Dobrovolskaya-Zavadskaya suggested that the pathology is associated with the loss of function of a certain gene that controls the development of the tail, which she called "gene T" (tail – tail) or Brachyury (short tail). This was TBXT. The gene encodes a protein important for the development of the chord in the embryo. Subsequently, it was shown that mutations in the coding part of the TBXT orthologs lead to the loss or shortening of the tail not only in mice, but also in cats, dogs, and zebrafish, while individuals homozygous for such mutations are usually not viable. By the way, it is because of this genetic feature that Manx cats have short tails.
The gene itself is very conservative in mammals, and this change is clearly not for nothing. But how does the insertion inside the intron, in the non-coding part, affect the work of the gene? The researchers noticed that in the fifth intron of the gene there is another Alu repeat - Alu Sx1, which occurs in all monkeys and, importantly, is located "backwards" relative to our AluY, that is, in reverse sequence. This means that in the RNA molecule formed during transcription of the TBXT gene, Alu Sx1 and AluY can "stick together", forming a loop. The easiest way to understand how this happens is by looking at the picture. Inside the loop is the sixth exon, that is, a piece of the coding part of the TBXT gene. Thus, the sixth exon "drops out", it does not participate in the formation of the protein. It turns out an alternative version of the gene, which the researchers designated TBXT-Δexon6.
The researchers were convinced that this is exactly the option that humans have and is absent in mice.
Then, on human embryonic stem cells, the experimenters showed that if the element AluY or its "brother" Alu Sx1 is removed from the TBXT gene, the TBXT-Δexon6 protein variant is not formed.
So maybe it is the TBXT-Δexon6 protein that is associated with impaired tail development?
To test this hypothesis, the researchers used genetic engineering methods to obtain mice in which the sixth exon was cut out of one of the copies of the TBXT gene. In 21 of 63 of these mice, the tail developed abnormally: it was either shortened or curved, and in 4 individuals it was absent altogether. Of course, it should be emphasized that not all mouse tails were affected. However, the researchers were convinced that the presence of the TBXT-Δexon6 variant is enough to lose the tail.
And the experiment also showed that homozygous owners of the mutation are not viable: embryos were either formed with a delay, or they developed spinal cord pathologies incompatible with life.
This, of course, is not irrefutable proof that this is how the tail disappeared from our ancestors, but such a scenario is very likely. Eureka! After all, this means that the ancient anthropoids lost their tail very quickly, it did not take thousands of generations. Some monkey – the "lucky" carrier of the AluY repeat in the TBXT gene - was born short–tailed 25 million years ago, and for some reason this feature turned out to be so useful that it spread among all its descendants.
Surprisingly, one mutation, and in the non-coding part of the genome, was enough for such a strong change. Let me remind you that there are 1 million Alu repeats in our genome, and more than 60% of them sit in introns.
Of course, using the example of mice, we see that the same mutation manifests itself in the structure of different individuals in different ways. Perhaps it was the same with our ancestors: for some time in the population of ancient hominoids there were both short-tailed and crooked-tailed, and changes in dozens of other genes affecting the same trait were required to consolidate complete "taillessness". And also pay attention to the pathology of the neural tube in homozygous mice. The advantage given to our ancestors by the absence of a tail must be very, very strong to outweigh the risk of getting something like spina bifida. In humans, the development of such pathologies may indeed be associated with mutations in TBXT.
"Thus, we assume that the evolutionary trade–off associated with the loss of the tail about 25 million years ago continues to affect health today," the authors conclude.
Portal "Eternal youth" http://vechnayamolodost.ru