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Sunday, July 3, 2011

RNA/DNA discrepancies

Vivian Cheung of the University of Pennsylvania and her colleagues from that school, the University of North Carolina and the Howard Hughes Medical Institute have found a large number of discrepancies between DNA sequences and their corresponding RNAs. These disparities could have implications for disease susceptibility and other factors of variability between people.

In the standard model of protein synthesis, the sequence of nucletotides in DNA is faithfully copied into RNA, which in turn is used to create the exact sequence of amino acids specified by that DNA. Apart from substituting U’s for T’s and some splicing, the RNA sequence is supposed to be virtually identical to the DNA template from which it was made. After all, our proteins are determined by our genes, aren’t they?

While this mechanism still holds true, the adherence between DNA sequence and protein structure isn’t as solid as once thought. It turns out that there are many discrepancies between RNA and DNA. In a sample of B cells from 27 people, Cheung and her colleagues found over 10,000 of these single nucleotide changes (RNA-DNA differences, or RDDs). 40% of the genes in the B cells had at least one RDD. RDDs were also found in skin and brain cells from both infants and adults. Interestingly, the RDDs did not appear to be random. Individuals who had an RDD at a specific location in one cell, such as a C where an A should have been according to the DNA sequence, had that same change to a C at the same place in all their cells.

Although there are enzymes (deaminases) that alter RNA sequences as compared to their DNA templates, these enzymes cannot account for nearly half of the RDDs discovered by the team. As of now, the mechanism behind those changes remains unknown.

These data bring into question just how much we can know about ourselves from sequencing our genomes. Thanks to the RDDs, two individuals with the same DNA sequence might very well end up with different proteins, and consequently, different health risks or physical or mental attributes.

Top: Comparison of a single-stranded RNA and a double-stranded DNA with their corresponding nucleotides.
By Sponk, 3/23/2010.