Alan Lambowitz a Professor of Molecular Biology and Director of the Institute of Molecular and Cellular Biology, University of Texas at Austin, explains:

“Introns are mysterious elements in evolution. Until the 1970s it was believed that genes in all organisms would be continuous and that they would make a continuous RNA, which would then get translated into a continuous protein. It was found, however, that most genes of the eukaryotes, the higher organisms including humans, aren’t like that at all. Most of the genes in higher organism are discontinuous. They consist of DNA coding regions that are separated by areas known as introns.”

“Genomes become loaded down with these introns, which are thought to have evolved from genomic parasites that existed for their own benefit and could spread without killing the host organism. It remains a major question in evolution as to why these introns exist, and how they came to compose such a large part of the human genome,” said Lambowitz.

Intron Secondary Structure in RNA. Click image for more info.

It’s a grand mystery, all right.  Genetics, epigenetics and the intron effect make the field of genetic sciences fascinating, time consuming and inevitably a source of many wonders to come.

Lambowitz and Georg Mohr began investigating Thermosynechococcus elongatus, a cyanobacterium that can survive at temperatures up to 150º F, after they noticed an unusually high percentage of the bacteria’s genetic sequence was composed of elements known as group II introns. These bacteria were found living in hot springs in Japan and may help solve one of the mysteries of the early evolution of complex organisms.  Lambowitz and Mohr’s study publishes free online this week in PLoS Biology. The bacterium has lessons and perhaps resources key to 21st century biofuel production.

In order to better understand the early history of introns, Lambowitz and Mohr have focused their investigation on bacteria because they’re believed to be the original evolutionary wellspring of the introns. They’re looking at T. elongatus in particular because it’s the only known bacteria in which introns have proliferated in a manner similar to that in higher organisms, such as humans.

Mohr, a colleague research scientist in Lambowitz’s lab explains, “We can’t go back a billion years in a time machine to see how introns proliferated in the early eukaryotes. What we can do is investigate the mechanisms that have allowed introns to proliferate in this organism, and try to infer how they evolved in eukaryotes, like humans, in which as much as 40 percent of the genome is made up of introns.”

As the pair’s work progressed, one of mechanisms they’ve identified, perhaps the most surprising, has been that heat plays a significant role in allowing introns to proliferate in T. elongatus. High temperatures, like those found in the hot springs in which the bacteria live, can unwind the DNA strands in the genome and make it easier for the introns to insert themselves.

Lambowitz expounds on the heat impact with a preliminary thought: This evidence of “DNA melting” is particularly suggestive when trying to imagine how introns proliferated in early eukaryotes, because the earth was hotter a billion or so years ago, when the early eukaryotes emerged. The genomes of the early eukaryotes may have begun with only a few introns, but over time, thanks in part to the high temperatures, the introns could have proliferated rapidly.  It’s a good starting point kind of idea.

The steak of the discovery and perhaps an early use may prove an enormous boon to researchers who are trying to use other high-temperature (“thermophilic”) bacteria to improve the efficiency of biofuels.  While we observers don’t get to hear about the experiments that don’t work out there must a lot of ideas that should have worked in genetic engineering that didn’t.  A better handle on the intron or the control of them or perhaps adding them in an engineered design is a high probability aspect of the best ideas we will see in the coming years.

Lambowitz has a real world example, “There’s one bacterial species in particular, which lives at high temperature and is very good at converting cellulose to ethanol, but has been intractable to genetic manipulation. The Department of Energy has a considerable amount of money invested in it, and they need to improve the strains but haven’t been able to do it. When we discovered these thermophilic introns, which work better at high temperatures, we were able to adapt them pretty rapidly for gene targeting.”  The intron is on its way into genetic engineering.

The technology for using group II introns in gene targeting, known as “targetron” technology, was pioneered by Lambowitz and his coworkers. Lambowitz and Mohr are already working with scientists at Oak Ridge National Laboratory to see if they can successfully genetically engineer thermophilic bacteria for increased biofuel production. They also foresee applying what they’ve discovered about T. elongatus introns and temperature to a whole range of biotech and biomedical applications that involve organisms and enzymes that function best at high temperatures.

Meanwhile the pair is still planning to delve further into the more profound, basic scientific questions that drew them to the subject in the first place.

While introns are seemingly obscure parts of the DNA chain they could prove to be the segment of the engineering opportunity that really puts the biology effort for bio products into high gear.  Much is yet to be discovered, but take note that this level of research is where the Nobel committee should be looking for prizewinners.

Just how all the parts, DNA, RNA, epigenetic effects and the influence of introns fit together promises to be the most interesting story of the 21st century – so far.  What else might be in the manual of life in every cell that will be discovered and put to work is up for research – let the most creative, and inquisitive minds go forth in to the source of the biological universe of life.


13 Comments so far

  1. Other Art on August 20, 2010 3:20 AM

    In addition, the proper gene signals must be identified, RNA molecules must be bound to ribosomes, and the presence of introns must be considered.

  2. Alfred on August 20, 2010 3:25 AM

    The remaining pieces of mRNA, called exons , are then spliced to form the final mRNA molecule.

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