29 March 2012

The Reality of Gene Expression is Not Politically Correct

UC San Francisco scientists are clarifying yet another aspect of gene expression, which makes humans distinctly different from each other and from other species. Once considered unimportant, "silent mutations" which change one "DNA letter" but leave the gene product unchanged, have recently been found to make a difference -- sometimes a big difference. The UCSF researchers are starting to discover why.
Table of Codons
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.

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 andMolecular Pharmacology.

"We didn't understand much about the rules," he added, but the new work suggests nature selects among redundant codons based on genetic speed as well as genetic meaning.

proteins made from genes containing particular sequences (referred to technically as Shine-Dalgarno sequences) were produced more slowly than identical proteins made from genes with different but redundant codons. They showed that they could introduce pauses into protein production by introducing such sequences into genes.

What the scientists hypothesize is that the pausing exists as part of a regulatory mechanism that ensures proper checks — so that cells don't produce proteins at the wrong time or in the wrong abundance.

A Primer on DNA Codons

All life on earth relies on the storage of genetic information in DNA (or in the case of some viruses, RNA) and the expression of that DNA into proteins to build the components of cells and carry out all life's genetic instructions.

Every living cell in every tissue inside every organism on Earth is constantly expressing genes and translating them into proteins—from our earliest to our dying days. A significant amount of the energy we burn fuels nothing more than this fundamental process.

The genetic code is basically a universal set of instructions for translating DNA into proteins. DNA genes are composed of four types of molecules, known as bases or nucleotides (often represented by the four letters A, G, T and C). But proteins are strings of 20 different types of amino acids.

To code for all 20 amino acids, the genetic code calls for genes to be expressed by reading groups of three letters of DNA at a time for every one amino acid in a protein. These triplets of DNA letters are called codons. But because there are 64 possible ways to arrange three bases of DNA together — and only 20 amino acids used by life — the number of codons exceeds the demand. So several of these 64 codons code for the same amino acid.

Scientists have known about this redundancy for 50 years, but in recent years, as more and more genomes from creatures as diverse as domestic dogs to wild rice have been decoded, scientists have come to appreciate that not all redundant codons are equal.
It is still politically correct to say that all modern humans share 99.9% of their genes with each other, although science has since proved that to be wrong. It is also commonly stated that humans share 99% of their genes with chimpanzees. But when the crucial subtleties of gene expression are taken into account, these PC truisms are patently false. Even identical twins can differ significantly, in terms of gene expression.

Besides the issue of redundant codons discussed above, there are issues of "copy number variants," transposon jumping genes, non-coding RNA, non-coding DNA, transcription factor variation, and a host of other mechanisms of gene expression variation yet to be discovered, elucidated, and clarified.

There is far more room for variation in the genome and epigenome than was understood just a decade ago or less. This is true for individual differences, just as it is true for gender and ethnic differences of gene expression and phenotype variation. There is no longer any excuse for intelligent and well-read persons to claim that humans have no significant genetic differences.

Reality is not politically correct, so it becomes politically expedient to abolish reality. Good luck with that.


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“During times of universal deceit, telling the truth becomes a revolutionary act” _George Orwell

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