Introns: what are they and why bother?

All living organisms rely on the exquisite structure of DNA to survive, thrive, and reproduce. Despite tremendous progress in the field of evolutionary biology thanks to Mendel, Darwin, Dobzhansky, Mayr, and others, it wasn’t until 1953—63 short years ago!—that Watson and Crick published a paper describing the structure of DNA. Building on the work of many others, including the often overlooked x-ray crystallography of Rosalind Franklin, Watson and Crick described a double helix structure with a backbone made of sugars and phosphates attached to nitrogenous bases united in the center by hydrogen bonds. Each of the nitrogenous bases is either a purine (i.e., adenine – A or guanine – G) or pyrimidine (i.e., thymine – T or cytosine – C), and they are arranged such that A pairs with T while G pairs with C. The structure of DNA, including its complementary base pairs and reverse polarity, makes it quite easy to see how the molecule could “unzip” for replication (Futuyma 1998).

 

 

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Watson and Crick (left and right, respectively) with their 1953 model. (Image from dataphys.org)
DNA
DNA structure – (a) double helix and (b) sugar phosphate backbone with nitrogenous bases joined by hydrogen bonds (Image from cnx.org)

While this information is likely review for most readers, the complexities of DNA’s structure and function become nearly infinite from this point forward, and despite tremendous advances, our understanding is still quite limited in many ways. One of the more interesting and historically mysterious aspects of DNA, especially in humans, is the existence of non-coding regions. Simply put, DNA is a sequence of many base pairs that get transcribed into mRNA, and when the mRNA is read in groups of three base pairs, codons are formed that dictate the translation of a specific amino acid. These amino acids then join together to form a specific protein. This process is often referred to as the Central Dogma of Molecular Biology (Crick 1970). The segment of DNA that codes for a specific polypeptide, which may be part or all of a protein, is called a gene (Futuyma 1998). Interestingly, within the gene there are regions that serve a purpose for coding, called exons, and regions that are non-coding, called introns. It is easy to remember which is which if you think about the fact that the information in the coding regions, exons, exits the nucleus before translation!

 

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Stepping through the Central Dogma of Molecular Biology. (Image from en.citizendium.org, Thomas Wright Sulcer)

You may be wondering at this point, as I often have, what is the point of having non-coding regions of DNA?!? This means more DNA to replicate and more DNA to create and fix; all of this means more energy and resources are devoted to a seemingly useless part of the molecule. A single human gene can have up to 8 introns, and the transcription of a single one of these can take hours to complete, meaning introns are quite costly to keep up (Chorev and Carmel 2012)! Research in recent years, however, suggests that these non-coding introns may not be so useless after all.

One somewhat obvious use of having non-coding regions interspersed throughout coding regions in genes hinges on the Central Dogma of Molecular Biology mentioned above. When genes are transcribed into mRNA only certain parts of the genes are transcribed, and this enables a small number of genes to code for a much larger number of proteins. Having the coding region broken up into smaller pieces by the insertion of introns allows for a far greater number of combinations of these coding regions, or exons, to be made (Nilsen and Graveley 2010). Further, research shows that in eukaryotes, genes with introns tend to produce more proteins than they do if their introns are removed (Buchman and Berg 1988). This may be because introns have components that promote or regulate the transcription of DNA to mRNA, such as enhancers and silencers (Chorev and Carmel 2012). Thinking back on the amount of time that it takes to transcribe some introns, some researchers also suggest that this delay could actually be an important pause in the time that a protein appears after a gene is activated, which could be especially important for developmental processes (Swinburne et al. 2008).

While this is by no means a comprehensive treatment of introns, hopefully it fueled your interest to learn more about this fascinating aspect of our DNA!

 

References

Buchman, A.R. and P. Berg. 1988. Comparison of intron-dependent and intron-independent gene expression. Molecular and Cellular Biology 8(10): 4395-4405.

Chorev, M. and L. Carmel. 2012. The function of introns. Frontiers in Genetics 3:55.

Crick, F. 1970. Central dogma of molecular biology. Nature 227: 561-563.

Futuyma, D. 1998. Evolutionary Biology, Third Edition. Sinauer Associates, Inc. Sunderland, Massachusetts.

Nilsen, T.W. and B.R. Graveley. Expansion of the eukaryotic proteome by alternative splicing. Nature 463: 457-463.

Swinburne, I.A., Miguez, D.G., Landgraf, D., and P.A. Silver. Intron length increases oscillatory periods of gene expression in animal cells. Genes and Development 22:2342-2346.