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Rare Evolutionary Event Detected in University of Texas Lab

Rare Evolutionary Event Detected in University of Texas Lab

It took nearly a half trillion tries before researchers at The University of Texas at Austin witnessed a rare event and perhaps solved an evolutionary puzzle about how introns – noncoding sequences of DNA located within genes – multiply in a genome.

Budding yeast added new noncoding genetic material

The results, published today in the Proceedings of the National Academy of Sciences, address fundamental questions about the evolution of new species and could expand our understanding of gene expression and the causes of diseases such as cancer.

"Until now, the only way researchers could track the evolution of introns was through phylogenetic analysis, which is examining the evolutionary relationships among sets of related organisms," says Scott Stevens, associate professor of molecular biosciences. "Our work is the first experimental verification that shows how introns can be transposed into an organism."

For a long time, scientists have known that much of the DNA within any given organism's genome does not code for functional molecules or protein. However, recent research has found that these genetic sequences, misnamed "junk" DNA in the past, often do have functional significance.

These introns are no exception. Now known to play a role in gene expression, introns are the portion of gene sequences that are removed or spliced out of RNA before genes are translated into protein. When eukaryotes first diverged from bacteria, there was a massive invasion of introns into the genome. All living eukaryotes — from yeast to mammals — share this common ancestor, and whereas simple organisms such as yeast have eliminated most of their introns, organisms such as mammals have considerably expanded their intron inventory. Humans have more than 200,000 introns that take up about 40 percent of the genome.

In the current paper, Stevens and co-author Sujin Lee, a former graduate student in cellular and molecular biology at UT Austin, used a new reporter assay to directly detect the loss and gain of introns in budding yeast (Saccharomyces cerevisiae). The team tested nearly a half trillion yeast and found only two instances in which an intron was added to a new gene. The proposed mechanism for this addition is a reversal of a splicing reaction.

Normally, to make proteins, RNA is read from the instructions in DNA, and the introns are spliced out. But in these two instances, the cell allowed the spliced out introns to make it back into a different RNA and was recombined back into the genome, thus creating a permanent genetic change. These are called intron gains, and if these accumulate over time, they can contribute to the development of new species as well as human disease.

"We showed in this project that introns continue to be gained, although infrequently at any point in time," says Stevens. "But can introns drive evolution? If these sequences give organisms a selective advantage and become fixed in a population, others have shown that it can be a major factor in the creation of new species."

These evolutionary advances come at a cost, however, because diseases such as cancer correlate with the improper removal of introns from RNA. Stevens adds, "We are continuing this work to further understand how this process impacts our genetic history, our future, and the prospects of curing disease."

The Department of Molecular Biosciences at The University of Texas at Austin funded this research. Screening was assisted by students in the Vertebrate Interactome Stream of the Freshman Research Initiative.
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Comments 2

 
Guest - Renata on Tuesday, 24 May 2016 04:14

I'm curious...How the mRNA is recombined back into the genome?

I'm curious...How the mRNA is recombined back into the genome?
Kristin E Phillips on Tuesday, 24 May 2016 11:00

Reverse splicing and subsequent reverse transcription by a cellular reverse transcriptase generate the cDNA copy containing the newly inserted intron.

Homologous recombination between the genome and cDNA copy yields a new intron gain allele.

//cns.utexas.edu/images/easyblog_shared/2016/b2ap3_thumbnail_Adding-intron-to-genome.jpg

Reverse splicing and subsequent reverse transcription by a cellular reverse transcriptase generate the cDNA copy containing the newly inserted intron. Homologous recombination between the genome and cDNA copy yields a new intron gain allele. [img]//cns.utexas.edu/images/easyblog_shared/2016/b2ap3_thumbnail_Adding-intron-to-genome.jpg[/img]
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