Slime is everywhere. Shape the texture of your body fluids, from the saliva in your mouth to the goo that covers your organs. It protects you from pathogens, including coronavirus, while creating a home in your mouth for billions of friendly bacteria. Help snails have sex Spiderman hanging from walls, hagfish turn water into a rapidly expanding goo, lampreys filter their food and swifts build nests.
But while slime is essential to all forms of complex life, its evolutionary origins have remained obscure.
I am an evolutionary geneticist who studies how humans and their genomes evolve. Together with my colleagues, including my longtime co-worker Stefan Ruhl and my student Petar Pajic, we addressed this evolutionary conundrum in our recently published article. We started by looking at how salivary slime is produced in different species. What we found is that slime opens a window into the role that repetitive DNA plays in the mysteries of evolution.
What are mucins?
Slime is made up of proteins called mucins, which are vessels for sugar molecules. These sugars are the main masters of making things slimy.
Unlike other proteins, which typically have complex 3D shapes, mucins often take the form of long, stiff rods. The sugar molecules are attached along the length of the rods, creating complex brush-like structures.
This collaboration between the constituent elements of proteins and the sugars linked to them, repeated over and over again, is essential for the properties of the mucins. These structures can adhere to other mucins and microbes, changing the physical properties of the fluids surrounding them into a viscous, viscous substance.
The evolution of the slime
Despite the remarkable properties of mucins and their essential role in biology, how they evolved has escaped scientists.
To begin understanding the evolutionary origins of mucins, my colleagues and I began looking for common genetic ancestors for mucins in 49 mammal species. After all, evolution often fumbles, but rarely invents. The simplest way to evolve a new gene is to copy and paste an existing one and make small changes to the new copy to adapt it to environmental circumstances. The chances of a species independently inventing a complex mucin from scratch are astronomically small. Our research team was confident that copying and pasting existing mucin genes that then adapt to the needs of a particular species was the main driver of mucin evolution.
But our initial assumptions turned out to be incomplete. Copying and pasting mucin genes into a genome should lead to child genes that have similarities to each other. While some mucins met our criteria, a previous study looked at all known genes that code for mucins in people and found a number of “orphaned” mucins that don’t belong to any gene family. They exist on their own in the vast landscape of the human genome.
We then focused on finding such orphaned genes in the genomes of dozens of species in the genetic databases. We found 15 cases of new mucin genes that evolved in different mammals, devoid of any connection with known mucin genes.
Further investigation, however, revealed that these mucin genes have relatives after all. They share ancestry with other rod-shaped proteins rich in the amino acid proline, which is commonly found in saliva. These proline-rich proteins, however, lack the major repetitive protein structures that help mucins bind to sugar molecules.
We hypothesized that these proline-rich proteins could undergo “mucinization” by repeatedly adding proteins that bind to sugar molecules, called glycoproteins. To test this, we compared the sequences of genes that code for mucins and genes that code for proline-rich proteins in different mammals, including people. We found that the sequences were very similar. The only difference was the presence of repeated segments of glycoproteins in the mucins. This meant that some proteins could be turned into mucins simply by adding copies of these repeating segments.
Repetitive DNA and evolution
Our results reveal the diversity of mucins in an entire type of creature, opening a glimpse into the slimy playing field of evolution’s adaptation.
Researchers often ignore repetitive genetic sequences because they are rarely found within genes that code for proteins that perform many biological functions in cells. But in the case of mucins, creating repetitive sequences from scratch turns out to be an important engine for their evolution. Our previous work on primates suggests that the number of repeating sugar-binding segments present in a given mucin may be the factor that determines its differences from others.
It is possible that the addition of repetitive genetic sequences could also discreetly model other functions in the genome as well. Indeed, such tandem repeats are a common type of mutation in the human genome, and recent studies suggest their unknown role in biological variation between people.