April 01, 2012
Silent Genetic Variants Not So Silent After All

So-called silent mutations in coding regions of DNA change how fast proteins get produced from the RNA that is translated from DNA. So the silent mutations aren't so silent after all. Generations of biology students have been misinformed.

By measuring the rate of protein production in bacteria, the team discovered that slight genetic alterations could have a dramatic effect. This was true even for seemingly insignificant genetic changes known as “silent mutations,” which swap out a single DNA letter without changing the ultimate gene product. To their surprise, the scientists found these changes can slow the protein production process to one-tenth of its normal speed or less.

Each amino acid in a protein (really in a peptide) gets coded for genetically by a 3 letter sequence of DNA called a codon. Since there are about 3 times as many codons as there are amino acids many triplet sequences code for the same amino acid. So, for example, ATT, ATC, and ATA all code for the amino acid isoleucine. For decades the prevailing view was that it did not matter whether ATT, ATC, or ATA was found in a genetic sequence. But doubts about that view rose (see below) due to a flood of genetic data showing that the silent variations were not evenly distributed as would be expected if they had equal effects. This research provides an explanation: The supposedly redundant codons get translated into /p>

Codon triplets that code for the same amino acid do not all get read by ribosomal RNA to create peptides at the same speed - at least in bacteria.

As described today in the journal Nature, the speed change is caused by information contained in what are known as redundant codons — small pieces of DNA that form part of the genetic code. They were called “redundant” because they were previously thought to contain duplicative rather than unique instructions.

This new discovery challenges half a century of fundamental assumptions in biology. It may also help speed up the industrial production of proteins, which is crucial for making biofuels and biological drugs used to treat many common diseases, ranging from diabetes to cancer.

“The genetic code has been thought to be redundant, but redundant codons are clearly not identical,” said Jonathan Weissman, PhD, a Howard Hughes Medical Institute Investigator in the UCSF School of Medicine Department of Cellular and Molecular Pharmacology.

Cheaper DNA sequencing provided the raw data that led scientists to suspect that the so-called silent mutations were not so silent. Now we know at least one reason why.

Many organisms have a clear preference for one type of codon over another, even though the end result is the same. This begged the question the new research answered: if redundant codons do the same thing, why would nature prefer one to the other?

This particular discovery, as important as it is, seems less important than why the scientists were motivated to investigate this problem. The answer: Analysis of a flood of genetic data showed unexpected patterns in relative frequencies of codon triplets. We are living in the early stages of what is effectively the Great Genetic Data Flood. The costs of genetic sequencing started declining much more rapidly in 2008 and have dropped by about 6 orders of magnitude over the last 10 years. At least a couple of more orders of magnitude of cost drop are still to come and DNA sequencing will become so cheap that most of us will get our DNA sequenced some time in the next 5 years.

The Great Genetic Data Flood is going to provide clues that will lead to a very large number of other discoveries. My three biggest areas of interest: A) genetic variations that cause cognitive differences; B) genetic variations that enable cancer cells escape from the regulatory mechanisms that govern cell growth and movement; and C) genetic variants that impact life expectancy. My guess is the biggest benefits of cheap genetic sequencing in the next 5 years will come in the form of improvements in cancer treatments that target genetic mutations for cancer spread.

Share |      Randall Parker, 2012 April 01 09:58 PM  Bio Genetic Regulation

Done Gone Galt said at April 4, 2012 5:39 PM:

If this Great Genetic Data Flood should provide the means to engineer personality traits; I am glad I won't live to see all that is done with that knowledge.

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