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doi:10.1534/genetics.106.067199
A more recent version of this article appeared on May 1, 2007.
REGULAR RESEARCH PAPERS |
Experimental estimate of the abundance and effects of nearly neutral mutations in the RNA virus 
6
Christina L Burch 1*, Sebastien Guyader 1, Haipeng Shen 1 and Daniel Samarov 1
1 University of North Carolina
* To whom correspondence should be addressed. E-mail: cburch{at}bio.unc.edu.
Submitted on October 23, 2006
Revised on December 11, 2006
Accepted on 23 February 2007
Although the frequency and effects of neutral and nearly neutral mutations are critical to evolutionary patterns and processes governed by genetic drift, the small effects of such mutations make them difficult to study empirically. Here we present the results of a Mutation Accumulation experiment designed to assess the frequencies of deleterious mutations with undetectable effects. We promoted the accumulation of spontaneous mutations by subjecting independent lineages of the RNA virus 
6 to repeated population bottlenecks of a single individual. We measured fitness following every bottleneck to obtain a complete picture of the timing and effects of the accumulated mutations with detectable effects, and sequenced complete genomes to determine the number of mutations that were undetected by the fitness assays. To estimate the effects of the undetected mutations, we implemented a likelihood model developed for QTL data (Otto and Jones 2000) to estimate the number and effects of the undetected mutations from the measured number and effects of the detected mutations. Using this method we estimated a deleterious mutation rate of U = 0.028 and a gamma effects distribution with mean s = 0.066 and coefficient of variation 
= 0.162. Although our estimates of U and s fall within the range of recent mutation rate and effect estimates in eukaryotes, the fraction of mutations with detectable effects on laboratory fitness (39%) appears to be far higher in 6 than in eukaryotes.
Key Words: RNA virus, mutation accumulation, nearly neutral, spontaneous deleterious mutation
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