Posted by jlwile on June 11, 2010
Before the human genome was sequenced, it was thought that humans had well over 100,000 genes. This reasonable conclusion was based on the fact that that the human body is estimated to produce 120,000 – 140,000 different proteins. Since biology had determined that a gene tells a cell how to make a protein, it was assumed that 120,000 – 140,000 proteins would require 120,000 – 140,000 different genes.
As is often the case with science, however, the data turned out to be very surprising. When the human genome was initially sequenced, it was estimated to contain about 30,000 genes. Today, it is thought that the human genome contains 20,000–25,000 genes.1
So if a human cell requires a gene in order to make a protein, and if the human body produces as many as 140,000 different proteins, how can it do so with “only” 20,000–25,000 genes? A large part of the answer to that question has to do with an amazing process called alternative splicing.
To understand alternative splicing, you need to first understand what a gene is and how it instructs the cell to make a protein. A gene is a stretch of DNA that essentially has a recipe for making a specific protein. The stretch of DNA is copied (actually a negative image is made) by a similar molecule called messenger RNA (abbreviated as mRNA). That mRNA then leaves the nucleus (where most of the cell’s DNA is found) and takes the copied recipe to a ribosome, where the protein is made according to the recipe found on the mRNA. That’s the overview of how a gene tells a cell to make a specific protein.
There are a few things I glossed over in that quick explanation, but I want to highlight one of them, because that’s where alternative splicing comes in. It turns out that the genes in human (and all eukaryotic) DNA are made up of sections called introns and exons. Initially, RNA makes a copy of all sections. At that point, it is called “pre-mRNA.” Before it leaves the nucleus to go to a ribosome, however, the introns are removed, as shown in the figure below:
The blue sections in the illustration represent introns, and the other sections represent exons. Before the pre-mRNA becomes mRNA and can leave the nucleus, the introns (blue sections) are removed, so that in the end, only the exons are left. This, of course, led many researchers to think that introns were useless “junk DNA.” After all, what possible purpose could they serve if their copies were removed before the mRNA left the nucleus? This, of course, fit nicely with Dr. Susumu Ohno’s concept that sections of junk DNA were leftover “fossils” of extinct DNA produced by the evolutionary process. As a result, the idea that introns are junk became very popular.
We now know that this idea is simply wrong. At least one of the functions that introns serve is to separate the exons so that one gene can code for many different proteins. Remember, there are only 20 – 25 thousand genes in the human genome, but they code for 120 – 140 thousand proteins. This happens because the exons in a single gene can be spliced together in different ways. Consider the figure below.
In the figure, the colored regions represent exons, and the black bars on the pre-mRNA represent introns. When the gene is originally copied, the introns and exons are both copied together, making the pre-mRNA. When the introns are removed from the pre-mRNA, the cell can use the exons as building blocks to make different proteins. In the illustration, the red exon, the yellow exon, and the blue exon are put together, making one protein. When the red exon, the green exon, and the blue exon are put together, however, a completely different protein is made. Thus, a single gene can produce more than one protein, because the exons can be put together in different ways. That’s alternative splicing, and it’s the major reason the human genome can have so few genes but code for so many proteins.
This, of course, is an amazingly elegant design. It takes a huge amount of information and compresses it into a small package. However, one important question should come to mind: “How often is this elegant design actually used?” In other words, do most genes participate in alternative splicing, or do just a few? The answer is we aren’t sure yet, but most studies indicate that up to 95% of the genes in the human genome participate in alternative splicing!2,3
Is that the only thing introns do? Are they just “spacers” that separate the exons so the exons can be spliced together in different ways? Probably not. You certainly wouldn’t expect that in such an elegantly-designed system. In the end, there are probably other jobs introns perform as well. As an article in the journal Science says:
Introns may play other vital roles, however. For instance, a slew of so-called small nucleolar RNAs (snoRNAs) are encoded by introns. Because snoRNAs accumulate in the nucleolus, where the protein-making ribosomes are formed, researchers speculate that they play a role in ribosome assembly.4
In addition, we know that certain introns play a vital role in the regulation of genes.5,6
So far from being the “junk” that many first imagined, introns are clearly a very important part of the genome. Indeed, as Dr. John S. Mattick, director of the Institute for Molecular Bioscience at the University of Queensland said:
The failure to recognize the full implications of this—particularly the possibility that the [introns] may be transmitting parallel information in the form of RNA molecules—may well go down as one of the biggest mistakes in the history of molecular biology
The more we learn about the genome, the less junk there appears to be. This, of course, supports the creationist view of the genome.
3. Qun Pan, et al., “Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing,” Nature Genetics 40:1413-1415, 2008 available online with subscription
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5. L Ottavio, et al., “Importance of introns in the growth regulation of mRNA levels of the proliferating cell nuclear antigen gene,” Mol Cell Biol 10:303-309, 1990
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6. A. B. Rose, “Intron-Mediated Regulation of Gene Expression,” Current Topics in Microbiology and Immunology 326:277-290, 2008
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