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DNA is the genetic code that provides the biological instructions for every living species, but not every bit of DNA helps the species survive. Some pieces of DNA are more like parasites, along for the ride and their own survival.

To translate DNA into proteins, the building blocks of life, many of these selfish DNA elements have to be removed from the genetic code. Doing so enables the body to produce the wide diversity of proteins that allow for complex life, but the process can also lead to health problems, like some kinds of cancer.

University of California, Santa Cruz researchers are studying the ways that these genetic elements hide and make copies of themselves, so they can propagate within a species' DNA, or even hop from one species to an unrelated one in a process called horizontal gene transfer.

A published in the Proceedings of the National Academy of Sciences proves that a type of genetic element called "introners" are the cause of many of these selfish genes spreading within and between species. It provides evidence for eight instances in which introners have transferred between unrelated species, the first proven examples of this phenomenon.

These results help us understand how genomes evolved to become so complex, and how we might take advantage of that complexity in human health research.

"[Introners are] a way that genome architectures and complexity arise, but not necessarily because there is natural selection that favors this complexity," said Russ Corbett-Detig, senior author on the study and professor of biomolecular engineering at the Baskin School of Engineering. "A few may ultimately benefit the host, but most are just cheaters that found a really good way to hide in the genome."

Investigating introners

Corbett-Detig and his former undergraduate student Landen Gozashti, now a postdoctoral fellow at UC Berkeley following a stellar Harvard Ph.D., have spent years studying introns, the segments of noncoding DNA that must be removed before proteins can be produced.

They wanted to figure out why these non-protein-coding bits of DNA are seen in varying amounts across all animals, plants, fungi, and protists, and how they have managed to so successfully replicate themselves and survive. It's long been a mystery of how all these introns first came to exist within DNA, as most don't seem to serve an evolutionary function.

Scientists are interested in this as a way to further understand genome evolution, but also because introns allow for a crucial process called "alternative splicing." Introns must be spliced out of the DNA sequence to create proteins, but this process can have variation and error, which means that different versions of a protein can be created from the same gene.

Ultimately this means that an organism can be more complex, but it also introduces the risk of health problems if splicing breaks a gene. Many researchers, including those at the UC Santa Cruz Genomics Institute, are studying how alternative splicing can be studied to better understand genetic disease. This research enhances the basic science of that health-related work.

In this study, the researchers have proven that introners are one of the main ways that new introns appear with a species' DNA. Introners are a kind of transposable element, a "jumping gene" that can move from part of a genome to another, that have found a way to successfully make copies of introns throughout a genome. The team's past work has suggested this, but their advanced methods of searching the DNA of a wide range of species has now allowed them to definitively confirm their hypothesis.

The researchers searched for introners in the DNA of thousands of species, something only recently made possible due to ongoing coordinated efforts to sequence a wide range of biodiversity and make the data publicly available, like the and the .

They found evidence for 1,093 families of introners among the 8,716 genomes they analyzed, suggesting that there are many kinds of introners out there capable of spreading introns through the genomes of various species.

"Because transposons are insanely diverse and present in basically every eukaryote, it implies that this really can be a very general way that new introns arise in different lineages," Corbett-Detig said.

These introners most commonly appeared in species of algae, fungi, and diverse single-celled eukaryotes, with an example found in a sea urchin and a tunicate, a tubular marine invertebrate.

Transfer between species

Among the many genomes they analyzed, the researchers found the first direct evidence for horizontal gene transfer of introners. They found eight examples of an introner hopping out of the genome of one species and settling into the genome of another unrelated species that mating could not explain.

In one case, the researchers found horizontal gene transfer between two species so unrelated that their last common ancestor was 1.6 billion years ago. In looking at the genomes of the two species—a sea sponge and a marine protist called a dinoflagellate—they found evidence that around 40 million years ago, an introner jumped from one of these species to the other.

The researchers hypothesize that the introners could be hitching a ride on giant viruses in order to transfer between species.

"That virus itself is a selfish element as well, so this is like a selfish element shuttling around on another selfish element," Corbett-Detig said.

Although eight examples of horizontal gene transfer may not seem like many, the researchers believe there would be many more if they kept looking within the 8.74 million species of eukaryotes that exist.

"Given how little of eukaryotic diversity we've sampled, I promise you that if we sampled the rest of them, we'd find many more," Corbett-Detig said.