Snot, a miracle of evolution

New mucus research has revealed that evolved in mammals many times and often surprisingly until it becomes like this viscous fluid that coats everything from slugs to saliva in the mouth, among other bodily fluids, according to what is published in the journal “Science Advances”.

The study focused on proteins called mucins, molecules with a variety of functions, primarily as components of mucus, where they contribute to the sticky consistency of the substance.

By comparing mucin genes in 49 mammalian species, scientists have identified 15 cases in which new mucins appear to have evolved through additive process which transformed a non-mucin protein into a mucin.

The scientists propose that each of these “mucinization” events it all started with a protein that wasn’t mucin. At some point, evolution added a new section to this non-mucin base: a section made up of a short chain of building blocks called amino acids that are decorated with sugar molecules. Over time, this new region duplicated and multiple copies were added to further elongate the protein, turning it into mucin.

The duplicated regions, called “repeats,” are essential for mucin function, say University at Buffalo researchers Omer Gokcumen and Stefan Ruhl, lead authors of the study, and Petar Pajic, first author.

Viscosity is key

The sugars that coat these sections stick out like the hairs of a bottle brush, giving mucins the viscous property that is vital for many of the important tasks these proteins perform.

“I don’t think it’s been known before that protein function can evolve in this way, from a protein gaining repeats. A protein that isn’t mucin becomes mucin just by gaining repeats. It’s an important way in which evolution does It’s an evolutionary trick, and now we’re documenting what’s happening again and again,” says Gokcumen, associate professor of biological sciences at UB College of Arts and Sciences.

The repeats we see in mucins are called “repeat PTS” for its high content of the amino acids proline, threonine and serine, and aids mucins in their important biological functions, which range from lubricating and protecting tissue surfaces to helping our food to be slippery and we can swallow it”, explains Stefan Ruhl, acting dean of the UB School of Dentistry and professor of oral biology.

“Beneficial microbes have evolved to live in surfaces covered with mucuswhile mucus can, at the same time, act as a protective barrier and defend against disease by shielding us from unwanted pathogenic intruders,” he adds.

“Few people know that the first purified and biochemically characterized mucin came from a salivary gland,” he adds, the microbiota of the oral cavity.

“I think this work is really interesting,” says Gokcumen. “It was one of those times when we got lucky. We were studying saliva, then we found something interesting and cool and decided to look into it.”

By studying saliva, the team realized that a small human salivary mucin, called MUC7, was not present in mice. However, rodents had a similar sized salivary mucin called MUC10. The scientists wanted to know if these two proteins were linked in a evolutionary perspective.

The answer was negative, but what the research found next was a surprise: Although MUC10 does not appear to be related to MUC7, a protein found in human tears, called PROL1, shared part of the structure of MUC10. PROL1 looked a lot like MUC10, without the sugar-coated bottle-shaped repeats that make MUC10 a mucin.

“We think that, in some way, this tear gene ends up being reused,” says Gokcumen. “It acquires the repeats that give it the function of mucin, and now it is abundantly expressed in the saliva of mice and rats.”

Scientists wondered if other mucins could have formed in the same way. They began to investigate and discovered several examples of the same phenomenon. Although many mucins share a common ancestry among several groups of mammalsthe team documented 15 cases in which evolution appeared to have converted non-mucin proteins into mucins through the addition of PTS repeats.

Surprising trait of life

And it was “with a fairly conservative eye,” Gokcumen points out, noting that the study focused on one region of the genome of a few dozen mammalian species. Rate the slime of “surprising vital trait” and is curious whether the same evolutionary mechanism could have resulted in the formation of certain mucins in slugs, slug eels, and other creatures. More research is needed to find an answer.

“How the new functions of genes evolve is still a question that we ask ourselves today -adds Pajic, doctoral student in biological sciences at UB-. Thus, we join this discourse by providing proof of a new mechanism, in which gaining repeat sequences within a gene gives rise to a new function.”

“I think this could have even broader implications, both in understanding adaptive evolution and in the possible explanation of certain pathogenic variants,” he continued. “If these mucins continue to evolve from non-mucins over time in different species and at different times, that suggests there’s some sort of adaptive pressure that makes them beneficial. And then, on the other end of the spectrum, maybe if this mechanism gets ‘out of control’ – it happens too often, or in the wrong tissue – then maybe it can lead to diseases like certain cancers or mucosal diseases.”

Mucin study demonstrates how a long collaboration between evolutionary biologists and UB dental researchers contributes new knowledge about genes and proteins which are also important for human health.

“My team has been studying mucins for many decades, and my collaboration with Dr. Gokcumen has taken this research to a new level by revealing all this exciting new knowledge about their evolutionary genetics,” Ruhl said. “At this late stage in my career, it is also immensely rewarding to see the flame of scientific curiosity carried by a new generation of young researchers like Petar Pajic.”

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