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Using statistics to decipher secrets of natural mutation

A new mathematical approach for analyzing the complex, subtle patterns of natural mutation in DNA will, according to its developers, help biologists understand how mutation contributes to evolutionary change in mammals.

The researchers, Howard Hughes Medical Institute investigator Phil Green and his student Dick Hwang, published a description of their new analytical approach and an initial application August 3, 2004, in the online early edition of the Proceedings of the National Academy of Sciences. Both are at the University of Washington in Seattle.

"Understanding naturally occurring mutations has been of great interest because mutations are major drivers of evolution," said Green. "However, it's surprising how little is still known about their causes."

Previous studies have revealed a number of biases in the rates of different types of mutational change. These arise in part from the innate biochemical characteristics of the four DNA nucleotide units adenine, guanine, cytosine and thymine that affect their vulnerability to modification and the accuracy with which they are replicated when cells divide. Particular nucleotide sequences, for example cytosine-guanine (CpG) dinucleotides, form "hotspots" regions that are particularly vulnerable to alterations that convert one nucleotide to another, causing mutations.

To understand these biases, Hwang and Green sought to develop a flexible approach to analyze the process of "neutral DNA evolution," in regions thought to lack genes and other functionally important sequences. "If you want to get an unvarnished picture of the mutation process itself, uncorrupted by natural selection, you want to look at neutrally evolving DNA," said Green. "Mutations in DNA that is not functional should better represent the complete spectrum of naturally occurring mutations. Mutations are of course also occurring in the genes and those are of interest because they can create new phenotypes and cause variati
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Contact: Jennifer Michalowski
michalow@hhmi.org
301-215-8576
Howard Hughes Medical Institute
16-Aug-2004


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