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New research indicates that DNA sequence itself influences mutation rate
Date:5/24/2010

May 24, 2010 Genetic variation due to DNA mutation is a driving force of adaptation and evolution, as well as a contributing factor to disease. However, the mechanisms governing DNA mutation rate are not well understood. In a report published online today in Genome Research (http://www.genome.org), researchers have identified intrinsic properties of DNA that influence mutation rate, shedding light on mechanisms involved in genome maintenance and potentially disease.

Some DNA mutations are subject to natural selection, either conferring a biological advantage that is selected for, or a negative effect that is selected against. Mutations not under selection are said to be neutral, and the rate at which neutral mutations accumulate is reflective of the true DNA mutation rate. Researchers can estimate this mutation rate by comparing neutrally evolving sequences in species that share a common ancestor.

Interestingly, the neutral mutation rate can vary significantly between different regions of chromosomes. This suggests that the context of the DNA influences how rapidly it accumulates mutations. Sequence high in pairs of the bases C and G (CpGs) where the C's are chemically modified, have been positively correlated with mutation rate. However, the chemical modification of CpGs makes them prone to mutation themselves, and with time they are eliminated from neutrally evolving sequences. NIH researchers Jean-Claude Walser and Anthony Furano have taken advantage of this property to investigate the role of CpGs on the mutation rate of non-CpG DNA, by comparing "old" and "young" sequences.

Walser and Furano compared the CpG content and DNA changes in inactive L1 retrotransposons shared by humans and chimpanzees. These ancient DNA sequences that had previously expanded in our common ancestor to multiple copies interspersed throughout the genome, but are now extinct "DNA fossils" that are neutrally e
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Contact: Peggy Calicchia
calicchi@cshl.edu
516-422-4012
Cold Spring Harbor Laboratory
Source:Eurekalert

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