Analysis and implications of mutational variation |
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Authors: | Peter D Keightley Daniel L Halligan |
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Institution: | (1) Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, West Mains Road, Edinburgh, EH9 3JT, UK |
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Abstract: | Variation from new mutations is important for several questions in quantitative genetics. Key parameters are the genomic mutation
rate and the distribution of effects of mutations (DEM), which determine the amount of new quantitative variation that arises
per generation from mutation (V
M
). Here, we review methods and empirical results concerning mutation accumulation (MA) experiments that have shed light on
properties of mutations affecting quantitative traits. Surprisingly, most data on fitness traits from laboratory assays of
MA lines indicate that the DEM is platykurtic in form (i.e., substantially less leptokurtic than an exponential distribution),
and imply that most variation is produced by mutations of moderate to large effect. This finding contrasts with results from
MA or mutagenesis experiments in which mutational changes to the DNA can be assayed directly, which imply that the vast majority
of mutations have very small phenotypic effects, and that the distribution has a leptokurtic form. We compare these findings
with recent approaches that attempt to infer the DEM for fitness based on comparing the frequency spectra of segregating nucleotide
polymorphisms at putatively neutral and selected sites in population samples. When applied to data for humans and Drosophila, these analyses also indicate that the DEM is strongly leptokurtic. However, by combining the resultant estimates of parameters
of the DEM with estimates of the mutation rate per nucleotide, the predicted V
M
for fitness is only a tiny fraction of V
M
observed in MA experiments. This discrepancy can be explained if we postulate that a few deleterious mutations of large effect
contribute most of the mutational variation observed in MA experiments and that such mutations segregate at very low frequencies
in natural populations, and effectively are never seen in population samples. |
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Keywords: | Mutation Quantitative traits Fitness Distribution of effects |
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