How did we get all this mud? In mammals, proteins called mucins have evolved – again and again – co-opting non-mucin proteins in surprising ways, study finds – Genetics News

From slime-coating slugs to the saliva in our mouths, many slippery bodily fluids contain mucus. So how did this marvel of biology evolve?

In mammals, the answer is many times, and often surprisingly so, according to a new study of proteins called mucins. These molecules have various functions, but as a family they are known as components of mucus, where they contribute to the sticky consistency of the substance.

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

The scientists propose that each of these “mucinization” events started with a protein that was not 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, with multiple copies added to stretch the protein even further, making it a mucin.

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

The sugars covering these sections protrude outward like the hairs of a bottle brush, and they give mucins the viscous property that is vital for many of the important tasks these proteins perform.

The research will be published on August 26 in Scientific advances.

“I don’t think it’s been known before that protein function can evolve in this way, from a protein gaining repeat sequences. A protein that is not mucin becomes mucin simply by gaining repeats. It’s an important way that evolution mucks up It’s an evolutionary trick, and we’re now documenting it over and over again,” says Gokcumen, PhD, associate professor of biological sciences at UB College. of Arts and Sciences.

“The repeats we see in mucins are called ‘PTS repeats’ for their high content of the amino acids proline, threonine and serine, and they help mucins in their important biological functions that range from lubricating and protecting the surfaces of fabrics to make our food slippery. so we can swallow it,” says Stefan Ruhl, DDS, PhD, acting dean of UB’s dental school and professor of oral biology. “Beneficial microbes have evolved to live on mucus-covered surfaces, while mucus can simultaneously act as a protective barrier and defend against disease by shielding us from unwanted pathogenic intruders. »

“Few people know that the first mucin that was purified and biochemically characterized came from a salivary gland,” adds Ruhl. “My lab has been studying mucins in saliva for 30 years, mainly because they protect teeth from decay and because they help balance the microbiota in the oral cavity. »

The intriguing evolution of an “incredible life trait”

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

By studying saliva, the team noticed that a small salivary mucin in humans called MUC7 was not present in mice. Rodents, however, had a similarly sized salivary mucin called MUC10. The scientists wanted to know: were these two proteins evolutionarily related?

The answer was no. But what the research found next was a surprise. While MUC10 did not appear to be related to MUC7, a protein found in human tears called PROL1 shared part of MUC10’s structure. PROL1 looked a lot like MUC10, minus the sugar-coated bottle brush repeats that make MUC10 a mucin.

“We think that somehow this tear gene ends up being repurposed,” Gokcumen says. “It gains the repeats that give it mucin function, and it is now abundantly expressed in mouse and rat saliva. »

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 common ancestry among various mammalian groups, the team documented 15 cases in which evolution appears to have converted non-mucin proteins into mucins via the addition of PTS repeats.

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

“How new gene functions evolve is still a question we ask ourselves today,” says Pajic, a UB doctoral student in biological sciences. “Thus, we add to this discourse by providing evidence for a new mechanism, where obtaining repeat sequences within a gene gives rise to a new function. »

“I think this could have even broader implications, both for understanding adaptive evolution and for possibly explaining certain pathogenic variants,” adds Pajic. “If these mucins keep evolving from non-mucins over and over again in different species at different times, that suggests there is some sort of adaptive pressure that makes them beneficial. And then, on the other end of the spectrum, maybe if that mechanism is going to “go off the rails” – happening too much, or in the wrong tissue – then maybe it can lead to diseases like certain cancers or diseases of the mucous membranes. »

The mucin study demonstrates how a long-standing partnership between evolutionary biologists and UB dental researchers is yielding new insights into genes and proteins that are also important to 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 these exciting new insights into their evolutionary genetics,” Ruhl says. “At this late stage in my career, it is also extremely gratifying to see the flame of scientific curiosity being carried by a new generation of young researchers like Petar Pajic. »

Additional research co-authors include Shichen Shen, PhD, postdoctoral associate, and Jun Qu, PhD, professor, both in the Department of Pharmaceutical Sciences, UB School of Pharmacy and Pharmaceutical Sciences and the Center for excellence in Bioinformatics and Life Sciences; and Alison J. May, PhD, former postdoctoral researcher, and Sarah Knox, PhD, associate professor, both in the Department of Cell and Tissue Biology at the University of California, San Francisco School of Dentistry. May is now an assistant professor at the Icahn School of Medicine at Mount Sinai.

The scientists who conducted the study are supported by the US National Science Foundation, as well as the National Institute of Dental and Craniofacial Research and the National Cancer Institute, both part of the US National Institutes of Health .

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How did we get all this mud? In mammals, proteins called mucins have evolved – again and again – co-opting non-mucin proteins in surprising ways, study finds – Genetics News

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