How do we differ from chimpanzees?
Dozens of "gene managers" who make us human have been Discovered
Anatoly Glossev, Vesti
Biologists have made a breakthrough by identifying several dozen regulators unique to humans that control the work of genes. Their role in the evolution of our species can be very great.
The discovery is described in a scientific article published in the journal Nature Genetics (Lambert et al., Similarity regression predicts evolution of transcription factor sequence specificity).
As you know, the DNA molecule consists of two strands connected in a double helix. A DNA strand is a long chain built of individual blocks (nucleotides). A DNA strand can be compared to a long string, only there are only four "letters" (nucleotides) in its alphabet: adenine, cytosine, guanine and thymine (briefly A, C, G and T). For example, a fragment of a thread may look like this: ATSTSTAAGGTTSAGATT…
After deciphering the genome of the chimpanzee, our closest relative among modern animals, geneticists compared the DNA of the two species "letter by letter". Here a person has such and such a nucleotide in the first (second, tenth, millionth ...) position in the line, and what is the chimpanzee? It turned out that in 99% of cases the same. That is, our genomes differ only by 1%. By the way, this is only ten times more differences in genes than happens between different people (on average 0.1%).
But the idea of hiring a chimpanzee or marrying him, because he is 99% human, is unlikely to meet with understanding. How could just 1% of the genes produce such impressive differences between species? One answer is that some of these genes control the work of other genes.
As you know, a gene is an instruction for the synthesis of a protein molecule. This protein can be a building material, accelerate the necessary chemical reactions or do something else.
But there are special proteins called transcription factors (TF). Such a protein comes into contact with a DNA molecule and recognizes a certain "word" in the "string" of nucleotides. This "word" or a set of "words" constructed according to certain rules is called a motive.
Having recognized its motive, the TF attaches itself to it. By his presence, such a "guest" begins to influence the work of the genes that happen to be next to him. Thus, the gene encoding the TF itself actually controls the work of those genes next to which this TF will eventually turn out to be. Therefore, the genes encoding TF are called regulators.
Regulators can control the work of other regulators, and so on in several levels of hierarchy. Thus, a random mutation affecting the upper-level regulator can change the work of many genes that determine many signs of the organism. This is one of the mechanisms that allow evolution by mutations in individual genes to produce real revolutions in the structure of organisms.
It is not surprising that biologists have long been studying the question of how different transcription factors are in different animals. But until now, scientists have discovered an amazing uniformity.
Even in humans and drosophila flies (!), and even more so in humans and chimpanzees, the set of TF is almost the same. And until now, it was believed that almost identical TF are attached to the same motives. And since the DNA molecules of our species, as we remember, are very similar, the same genes are likely to be in the vicinity of this motif in humans and chimpanzees.
Divergence on target motives between TF of different types. Pie charts show the degree of similarity between TF of different classes in this species and the rest. Illustration by Sam Lambert; translated by Vesti.The science.
However, there was a flaw in this logical chain. A new study refutes the thesis that similar in structure TF are attached to the same motives. The first author of the article Samuel Lambert (Samuel Lambert) from the University of Toronto has developed a new method for comparing transcription factors among themselves.
Recall that a protein molecule is also a "string of letters", only the letters in this case are amino acids, and there are 20 of them in the alphabet. You can calculate how similar two TF are by comparing them "letter by letter". This is exactly how the previous algorithms worked.
But the amino acids that are in direct contact with DNA make up only a small part of the TF molecule. Meanwhile, it is they who first of all determine which motive the protein will "sit down" on. Figuratively, we can say that the motif is a lock, and the TF is a bulky structure from which a small key sticks out. Which lock will be opened determines the structure of the key, and not the surrounding aggregates.
This fact was taken into account in the new method. Calculating the degree of similarity of TF of different types, the computer gives more weight to the differences in those areas that directly bind to DNA (the "key to the lock").
This technique made it possible to find out that proteins, which according to previous counting methods turned out to be almost the same, actually fit together with different sections of DNA and, therefore, affect different genes.
"Even in closely related species, there is an important part of TF that can bind to different sequences [of nucleotides],– says Lambert. – This means that they may have different functions, regulating the work of different genes, which may be important for species differences."
So, it turned out that almost half of the motives that are targets for certain human TF do not attract the attention of drosophila transcription factors, and vice versa. Thus, the conclusions of previous studies about our almost complete similarity with flies in this matter seem to have turned out to be premature (which, of course, flatters humanity's self-esteem).
The difference between a human and a chimpanzee is not so impressive. But even here there were dozens of transcription factors unique to humans that affect the work of hundreds of genes.
"We believe that these molecular differences may be the reason for some of the differences between chimpanzees and humans," Lambert says.
Especially a lot of newly identified TF unique to humans turned out to be among zinc fingers. This is the name of proteins with a characteristic finger-like structure containing zinc ions.
The functions of these proteins have not yet been sufficiently studied. However, it is known that organisms with more diverse zinc fingers have more cell types. Cellular diversity may allow them to create more complex organs with subtle functions. It is possible that these proteins have played a role in the development of our unique brain and immune system for the animal world.
Zinc fingers also affect sexual dimorphism, that is, anatomical differences between males and females of the same species.
The exact functions of the TF found unique to humans have yet to be established. And it is unlikely that it will be easy to do, given that there are no such proteins in experimental animals.
By the way, the new results may be unpleasant news for many biologists. As you know, the best (and perhaps the only truly effective) method to find out the function of a particular gene is to "break" it and see how such a mutation will affect the experimental organism. Of course, no one will conduct such experiments on people, but experimenters take advantage of the fact that the vast majority of genes in humans and, say, mice coincide or almost coincide.
As it has now become clear, with genes encoding transcription factors, it is necessary to exercise increased caution, because their external similarity does not guarantee that TF attaches to the same motives and performs the same functions.
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