Spotlight on for underappreciated bodily fluids: Researchers have gained insight into the interesting evolution of mucus in mammals. In order to ensure the production of the vital secretions, some initially non-mucous proteins were apparently cleverly transformed into slime-forming substances - into so-called mucins - in the course of development. The scientists emphasize that the information about the basics of mucus formation can also be of importance for medicine.
Yuck slime! The slimy substance does not have a good image - but wrongly so. Because the viscous liquids fulfill extremely important functions in the body. Viewed objectively, we are actually downright slimy people: Every day, humans produce enormous amounts of the secretions that line large areas of the body – especially in the respiratory and digestive systems. The slime provides a slip effect there and protects the sensitive surfaces from drying out, dirt and pathogens. It also provides a home for the beneficial microbes in our bodies. If something is wrong with human mucus production, this can have correspondingly serious health consequences.
Because of this importance, slime has been the focus of science for some time. The researchers led by Stefan Ruh from the University at Buffalo in the US state of New York are also dedicating themselves to the topic. Specifically, they are working on the substances that turn liquids into mucus: mucins are glycoproteins that consist of a central protein chain and side chains of sugar compounds. These polysaccharides give the mucins their high water-binding capacity, which in turn is responsible for the typically slimy, gel-like consistency. In slimy secretions there are different versions of mucins that have special properties and functions. "For the past 30 years, my lab has been studying mucins in saliva, primarily because they protect teeth from tooth decay and help balance the microbiota in the oral cavity," says Ruh.
target mucilage
In the course of their research, the scientists noticed that there is a small salivary mucin called MUC7 in humans that, surprisingly, mice do not have. As was subsequently shown, however, the rodents instead have a similarly large salivary mucin called MUC10. It was therefore assumed that the two proteins are related to each other from an evolutionary point of view. But as the researchers discovered with surprise, this is not the case: the construction plan differed significantly. However, further research revealed that a protein found in human tears called PROL1 shares some of the structure of mouse MUC10: PROL1 looks very similar to MUC10, but lacks the mucus-forming sugar-coated repeats that make MUC10 a mucin.
"We therefore suspected that the tear gene was somehow repurposed during evolution," says senior author Omer Gokcumen of the University at Buffalo. It was apparently equipped with the typical genetic repeat sequences, which in turn are responsible for the formation of the mucin structures. The scientists wondered whether other mucins in mammals might also have formed from non-mucin proteins in this way. They followed this lead by examining mucin genes from 49 mammalian species.
Widespread “slimification”
As they report, they identified 15 cases in which new mucins apparently developed through “mucinization” from a protein that was not originally related to these substances. It is becoming apparent that in the process, new sections have been attached to the non-mucus base - more amino acids that are loaded with the "mucus-causing" sugar molecules. More copies then made the proteins longer and longer, ultimately turning them into mucins, the scientists explain. "The repeats we see in the mucins are termed 'PTS repeats' because of their high content of the amino acids proline, threonine and serine, and they help the mucins in their important biological functions of lubricating and protecting blood vessels tissue surfaces to support the lubricity of food,” says Ruhl.
The researchers suspect that this principle of "mucinization" of proteins - or the genes on which they are based - occurred frequently in the developmental history of mammals. They now want to investigate further whether the same evolutionary mechanism also drove the formation of some mucilage in other "mucilage" such as snails or fish. As the team concludes, studying mucus proteins and their history is not only interesting from an evolutionary point of view. "I think the field of research may have broader implications, both for understanding adaptive evolution and for possibly explaining certain disease-causing aspects," says lead author Petar Pajic from the University at Buffalo. "If mucins evolved again and again from non-mucins in different species at different times, this suggests that there is some kind of adaptive pressure that makes them advantageous. However, if this mechanism gets out of hand, it may lead to diseases such as certain types of cancer or mucosal diseases,” says Pajic.
Source: University at Buffalo, professional article: Science Advances, doi: 10.1126/sciadv.abm8757