deleterious mutation

Haag-Liautard C, Dorris M, Maside X, Macaskill S, Halligan DL, Houle D, Charlesworth B & Keightley PD 2007 Direct estimation of per nucleotide and genomic deleterious mutation rates in Drosophila. Nature 445:82-85.

  • from 37 mutation events that we detected, we obtained a mean estimate for u of 8.4 × 10−9 per generation
  • by multiplying u by an estimate of the fraction of mutations that are deleterious in natural populations of Drosophila10, we estimate that U is 1.2 per diploid genome
  • assuming that point mutations and indels are equally deleterious on average, the mean genomic deleterious mutation rate is U = 1.15 (95% CI 0.49–2.19)
  • indels are more likely to be strongly deleterious than point mutations
  • including this information gives a slightly higher estimate for U of 1.20 (95% CI 0.51–2.28; Table 2)
  • we found significant genetic variation in the mutation rate between genotypes
  • our estimate of the nucleotide site mutation rate is about 5-fold (95% confidence limits 2-fold and 12-fold) higher than a phylogenetic estimate from synonymous site divergence
  • assuming that wild flies undergo ten generations per year
  • this could be partly due to inaccurate estimates of species divergence times
  • or to differences in generation times between laboratory flies and wild flies
  • our estimate for u indicates that U probably exceeds one event per diploid genome per generation in Drosophila and is unlikely to be less than 0.5
  • this is comparable with an estimate in C. elegans based on direct sequencing
  • genomic deleterious mutation rates estimated from the divergence of fitness traits in MA lines strongly disagree between these species
  • about 0.01 in C. elegans
  • up to about 1.0 in Drosophila
  • it is unexpected that some Drosophila MA experiments should yield similar phenotypic6 and DNA-based (our study) estimates of U
  • the reasons for this discrepancy remain obscure
  • non-zero rates of recombination can be maintained by both Hill–Robertson interference11 and synergistic epistasis28
  • with genomic deleterious mutation rates as low as 0.5
  • (our lower confidence limit)
  • our estimate of U = 1.2 seems too low for deterministic selection against deleterious mutations to allow the maintenance of sexual reproduction with a twofold cost
  • although the mechanism might work if U were as high as our upper confidence limit