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Genetics, Vol. 167, 815-826, June 2004, Copyright © 2004
doi:10.1534/genetics.103.025262
Estimates of the Genomic Mutation Rate for Detrimental Alleles in Drosophila melanogaster
Brian Charlesworth1, Helen Borthwick, Carolina Bartolomé and Patricia Pignatelli2
Institute of Cell, Animal and Population Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom
1 Corresponding author: Institute for Cell, Animal and Population Biology, Ashworth Laboratories, King's Bldgs., University of Edinburgh, W. Mains Rd., Edinburgh EH9 3JT, United Kingdom.
E-mail: brian.charlesworth{at}ed.ac.uk
The net rate of mutation to deleterious but nonlethal alleles and the sizes of effects of these mutations are of great significance for many evolutionary questions. Here we describe three replicate experiments in which mutations have been accumulated on chromosome 3 of Drosophila melanogaster by means of single-male backcrosses of heterozygotes for a wild-type third chromosome. Egg-to-adult viability was assayed for nonlethal homozygous chromosomes. The rates of decline in mean and increase in variance (DM and DV, respectively) were estimated. Scaled up to the diploid whole genome, the mean DM for homozygous detrimental mutations over the three experiments was between 0.8 and 1.8%. The corresponding DV estimate was 
0.11%. Overall, the results suggest a lower bound estimate of at least 12% for the diploid per genome mutation rate for detrimentals. The upper bound estimates for the mean selection coefficient were between 2 and 10%, depending on the method used. Mutations with selection coefficients of at least a few percent must be the major contributors to the effects detected here and are likely to be caused mostly by transposable element insertions or indels.
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