There are many reasons for thinking that introns are mostly junk DNA.
Lately there's a new argument that seems to be taken seriously. Several labs have looked closely at the small number of essential introns in yeast and determined that some of them are essential because they contain other genes, such as snoRNA genes. There's another subset that contain some sort of regulatory sequences that help regulate the growth of yeast cells under starvation conditions (Morgan et al., 2019; Parenteau et al., 2019) [Yeast loses its introns].
The bottom line, as far as I'm concerned, is that something like 99.7% of all the introns in the ancestor of modern Baker's yeast were junk but there's a small number that have secondarily acquired a function.
Two of the authors of one of the papers cited above have looked at the same data and reached a very different conclusion.
Here's how they put it in their conclusion.
- The size and sequence of introns in related species are not conserved and almost all of the sequences are evolving at the rate expected for neutral substitutions and fixation by drift.
- Many species have lost introns or reduced their lengths drastically suggesting that the presence of large introns can be detrimental in some cases (probably large populations).
- After decades of searching, there are very few cases where introns and/or parts of introns have been shown to be essential.
- Researchers routinely construct intronless versions of eukaryotic genes and they function normally when re-inserted into the genome.
- Intron sequences are often littered with transposon and viral sequences that have inserted into the intron and this is not consistent with the idea that intron sequences are important.
- About 98% of the introns in modern yeast (Saccharomyces cerevisiae) have been eliminated during evolution form a common ancestor that probably had about 18,000 introns [Yeast loses its introns]. This suggests that there was no selective pressure to retain those introns over the past 100 million years.
- About 245/295 of the remaining introns in yeast have been artificially removed by researchers who are constructing an artificial yeast genome suggesting that over 80% of the introns that survived evolutionary loss are also junk [Yeast loses its introns].
Lately there's a new argument that seems to be taken seriously. Several labs have looked closely at the small number of essential introns in yeast and determined that some of them are essential because they contain other genes, such as snoRNA genes. There's another subset that contain some sort of regulatory sequences that help regulate the growth of yeast cells under starvation conditions (Morgan et al., 2019; Parenteau et al., 2019) [Yeast loses its introns].
The bottom line, as far as I'm concerned, is that something like 99.7% of all the introns in the ancestor of modern Baker's yeast were junk but there's a small number that have secondarily acquired a function.
Two of the authors of one of the papers cited above have looked at the same data and reached a very different conclusion.
Parenteau, J., and Elela, S. A. (2019) Introns: Good Day Junk Is Bad Day Treasure. TRENDS in Genetics. 35:923-934 [doi: 10.1016/j.tig.2019.09.010]Here's how they explain their stance in the paper's introduction.
Abstract: Introns are ubiquitous in eukaryotic transcripts. They are often viewed as junk RNA but the huge energetic burden of transcribing, removing, and degrading them suggests a significant evolutionary advantage. Ostensibly, an intron functions within the host pre-mRNA to regulate its splicing, transport, and degradation. However, recent studies have revealed an entirely new class of trans-acting functions where the presence of intronic RNA in the cell impacts the expression of other genes in trans. Here, we review possible new mechanisms of intron functions, with a focus on the role of yeast introns in regulating the cell growth response to starvation.
Clearly, removing introns correctly from pre-mRNAs is important but cannot explain their ubiquitous preservation in genomic DNA across the course of evolution. Certainly, they are not simply disposable junk. In organisms with large genomes, introns are indispensable for the process of alternative splicing, which is essential for regulating gene expression and function. However, introns are also preserved in organisms where alternative splicing and splicing-dependent regulation of gene expression are rare. Why would single cells with compact genomes tolerate the energetic cost of transcribing, splicing, and degrading introns if their only function is associated with the act of their removal? Could introns serve functions other than regulating the expression of host genes? In the past few years, sequencing advances and our ability to delete introns from eukaryotic genomes have started to provide answers to some of these questions. Introns are now known to provide a reservoir of small noncoding (nc)RNAs that act in trans on other genes. Recent studies have shown that intronic RNAs also function as direct regulators of multiple cell-response genes during nutrient depletion.This isn't a case of viewing a glass as either half full or half empty. It's a case of viewing a glass as either >99% empty (i.e. mostly junk) or ~1% full (i.e. mostly functional). The authors are ignoring all the evidence suggesting that introns are mostly junk and concentrating on the relatively few examples where they have acquired a function. They then extrapolate from these few examples to declare that introns in general are not junk.
Here's how they put it in their conclusion.
Modern introns are not junk DNA, but rather they are noncoding sequences that have gained functions through evolution to merit their maintenance. It is possible that a population bottleneck, or inability to eliminate introns, provided the initial reason for their preservation and allowed introns to develop these functions. However, it is becoming increasingly clear that these introns have rapidly gained inherent functions beyond regulating their host gene that further supported their maintenance through evolution.It seems obvious that none of the reviewers of this paper had a problem with such a conclusion. Am I the only one who sees a problem?
1. Alternative splicing is a common reason for thinking that introns are essential but we now know that alternative splicing isn't common so it can't account for the vast majority of introns.
Morgan, J.T., Fink, G.R., and Bartel, D.P. (2019) Excised linear introns regulate growth in yeast. Nature [doi: 10.1038/s41586-018-0828-1]
Parenteau, J., Maignon, L., Berthoumieux, M., Catala, M., Gagnon, V., and Elela, S.A. (2019) Introns are mediators of cell response to starvation. Nature. [doi: 10.1038/s41586-018-0859-1]
