Cellular Anthropology
Why don't we look like chimpanzees
Kirill Stasevich, "Science and Life"With all the similarity of the great apes with man himself, it is unlikely that anyone will confuse them with humans.
The strongest external differences between us and them are manifested in the face: the length of the nose, the length of the jaws, skin pigmentation and other facial parameters in chimpanzees, our closest relatives, are completely different than ours. Meanwhile, our genomes with chimpanzees are 98.7% similar. Until recently, it looked like a paradox: how, with such genetic similarity, two species can have such a different appearance. The answer here is that the same genes can work in different ways, that is, some gene in a monkey may be more active, and in a human – less, and it can turn on in different parts of the same organ.
The work of genes is controlled by numerous regulatory elements, some of which belong to the group of enhancers. This is the name of the sequences in DNA with which transcription factors bind, triggering the synthesis of RNA on the gene (which, in turn, then go to the ribosomes that assemble the polypeptide chain in accordance with the information copied from DNA into RNA). The enhancer itself does not encode anything, RNA is not synthesized on it, but the activity of a particular gene depends on how the enhancer interacts with transcription proteins. Researchers from Stanford University have suggested that the differences in appearance between humans and monkeys are rooted precisely in the fact that the enhancer sequences in the two species work differently (Scientists home in on origin of human, chimpanzee facial differences).
To test this, Sarah Prescott and her colleagues used cells of the so–called neural crest, a structure that appears in the early stages of embryo development. As the name implies, the crest gives rise to the elements of the nervous system, but, in addition, its stem cells are involved in the formation of the adrenal glands, skin pigment cells originate from them and they also form the cartilage of the facial skull. In the experiments, however, not real embryonic material was used, but induced stem cells: normal, specialized skin or blood was taken from humans and chimpanzees, which were then converted to a non-specialized, stem state by molecular and cellular methods. Then such rejuvenated cells were provided with instructions that guided them along the path of neural crest development, while simultaneously observing the activity of regulatory genetic elements in them.
In an article in Cell (Prescott et al., Enhancer Divergence and cis-Regulatory Evolution in the Human and Chimp Neural Crest), the authors write that most of the genetic regulators in human cells and in monkey cells were the same, but they really worked differently: about 1000 enhancers activity depended on the type of organism. Accordingly, the activity of genes under the control of enhancers also changed. For example, the PAX3 and PAX7 genes, which directly affect the length of the facial part of the skull and the pigmentation of the skin on the face, are present in both humans and chimpanzees, but they worked more strongly in chimpanzees. On the other hand, the BMP4 gene, which determines the shape of the jaws, worked more actively in humans. BMP4 is present in birds, fish, and other animals, and if its activity is artificially spurred, for example, in mice, the rodent's skull will become rounder, and the eyes will noticeably shift from the sides of the head to the front of the muzzle (we can say that the appearance of the mouse will slightly "humanize"). Stem cells, in which genes and their regulators begin to work differently, "sculpt a portrait" of future mice, humans or chimpanzees in a different way.
Diagram from the article in Cell – VM
The results obtained once again confirm the well-known theory that evolution does not invent new genes so much as it changes the way old ones are managed. Moreover, the changes in management are again connected not with the fact that new control elements have appeared (new enhancers, promoters, insulators, etc.), but with mutations in already existing regulators. On the example of humans and monkeys, geneticists from Cornell University showed this not so long ago: in a 2013 article in Nature Genetics, they said that if ordinary human genes received quite a few mutations during evolutionary development, then regulatory elements mutated very much compared to chimpanzees; and most of the mutational differences occurred in those areas that regulate the transcription of genes responsible for immunity, blood, the nervous system and some other processes.
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14.09.2015