A long-standing genomic mystery has been solved by scientists

A long-standing genomic mystery has been solved by scientists ...

Introns are non-coding DNA regions found in eukaryotic organisms. They are then transcribed into RNA but are removed before the final mRNA is formed. Introns are thought to have evolved as a way to broaden the amount of protein that can be produced from a single gene.

Researchers from UCSC believe that introns, an eukaryotes' unique molecular complexity, originate primarily from introners.

Introns, non-coding DNA segments that must be removed from genetic code before protein synthesis, are one of the most significant mysteries in biology. Despite their ubiquity, there are significant differences in the number of introns found in different species' genomes, even among closely related species.

A new research conducted by researchers at the University of California, Santa Cruz, has suggested that introners are the only plausible explanation for intron burst events, which occur when thousands of introns appear in a genome seemingly all at the same time. Evidence of this is also found in animals throughout the evolutionary tree of life.

Russell Corbett-Detig, an associate professor of biomolecular engineering and senior author of the research, believes "this study" provides a plausible explanation for the vast majority of intron origins.

“This is the only one that I know of that might generate thousands and thousands of introns all at the same time in the genome.”

Introns are important because they allow for alternative splicing, which allows one gene to code for many transcripts and thus perform many complex cellular functions. Introns can also affect gene expression, the rate at which genes are turned on to make proteins and other non-coding RNA. This is why certain cancers are caused by missed splicing.

Corbett-Detig and his colleagues sifted the genomes of 3,325 eukaryotic species — all of whom have access to high-quality reference genomes — to discover how common introner-derived introns are and in what groups of species they are most likely to be found.

From animals to single-cell protists, this evidence was found in many different species. They are thought to be both the fundamental and most widespread source of introns across the evolutionary tree.

"You see this in a pretty wide range of animals, which suggests it's a fairly general mechanism," Corbett-Detig said.

When it comes to evolutionary history, this analysis can only detect evidence of introner-dervied introns dating back a few million years. In some species, such as humans, in the earlier stages of this analysis, it's possible that intron bursts might have occurred at a time beyond the scope of this analysis — meaning this study probably greatly underestimates the true scope of introner-dervied introns across all eukaryotes.

Introners may be viewed as a parasite with the intention to survive and reproduce themselves in a new species. When an introner enters a new organism, that new host has never seen that element before and has no mechanism to defend itself.

Landen Gozashti, the study's first author who worked on the analysis methods as an undergraduate at UCSC and is now a graduate student at Harvard University, believes that everything in evolution is a conflict.

Introners discovered a way to have less impact on the host gene's fitness while preserving its effects throughout the generations of the host species' evolution by being spliced out of the DNA sequence.

Despite the fact that all introners were found across all species, the findings suggested that marine organisms were 6.5 times more likely to have introners than land animals.

This is likely to be the result of a phenomenon called horizontal gene transfer, in which genes are transferred from one species to another, rather than the usual vertical transfer through mating and the passing of genes from parent to child in marine environments.

Introners are able to travel this way because they belong to a group of genomic elements called transposable elements, which are able to transcend the cell environment in which they live, making them mechanistically well-equipped to cross species via horizontal gene transfer.

It's possible that land animals acquired introns from intron bursts long ago, considering that all species evolved from marine organisms.

“If your ancestors were marine organisms, which they were all, there’s a good possibility that a lot of your introns are some form of inherited from a similar [introner burst] event back then,” Corbett-Detig said.

More introners were also discovered in fungal species, which are also known to have higher rates of horizontal gene transfer, further supporting the notion that introner gain is a result of this phenomenon.

Corbett-Detig intends to look for similarities in two different species' horizontal gene transfer via nearly identical introners in future experiments. His algorithms will scan each new genome's introners and compare it to all of the known introners to see if there are any differences.

This research challenges one of the most fundamental genome evolution theories concerning what drives genomic complexity in eukaryotes. Furthermore, it claims that at a given point in evolution, many species had relatively small effective population sizes, meaning that very few organisms in a species were producing offspring to produce their next generation.

Introners, which are neutral to somewhat deleterious, would be more likely in populations with lower effective populations, according to the authors, but they found the opposite. For example, Symbiodinium, a protist known to have a much higher effective population size than humans, land plants, and other invertebrates, is the species that seems to be gaining the most introns.

This analysis shows that genome complexity arises not as a result of the genome itself, but as a result of the intrusive transposable element, the introner, as it attempts to spread. As introners and other elements struggle to survive and persist, this conflict drives genome complexity.

Introns' ability to respond to the negative effects of introns is also demonstrated in their ability to affect gene expression. Those who do have introners had a lower overall expression level when comparing them to genes without them.

Introners are not necessarily the cause of this decreased expression, but that genes that are less expressed have a higher tolerance for an element that might be affecting the species' survival, while genes that are highly expressed and may be coding for vital functions in the body may not tolerate the introduction of new introns that might interfere with their function.

Corbett-Detig's ongoing research on this topic involves looking at actual evidence of how individuals within a species react to intron bursts. He has identified several species that are experiencing ongoing intron bursts and is looking at the effect of introners on the cells' DNA and RNA. The species' evolutionary fitness

Landen Gozashti, Scott W. Roy, Alexander Kramer, Manuel Ares Jr., and Russell Corbett-Detig, Proceedings of the National Academy of Sciences, 19 October 2022 DOI: 10.1073/pnas.2209766119

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