deleterious mutation

Denver DR, Morris K, Lynch M & Thomas WK 2004 High mutation rate and predominance of insertions in the Caenorhabditis elegans nuclear genome. Nature 430:679-672.

• our sequence-based estimate of U_t (~2.1 mutations per haploid genome per generation) is about two orders of magnitude higher than the haploid deleterious genomic mutation rate (U_d) estimated by laboratory fitness assays with the same set of C. elegans MA lines
• (U_d < 0.015 mutations per haploid genome per generation)
• indicating that most mutations in the MA lines (more than 99%) might either be neutral or have deleterious effects too mild to be detected in laboratory fitness assays
• comparative analyses of Caenorhabditis genome sequences suggest that the vast majority of nonsynonymous mutations (~94% on the basis of a between-species K_a / K_s ratio of 0.06)²⁴ are sufficiently deleterious for selection to act against them in nature
• fitness-based estimates of U_d are known to be highly dependent on environmental conditions
• if we consider only nonsynonymous base substitution mutations and indels in exon sequence, the mutation rate reported here coupled with the K_a / K_s data for Caenorhabditis yields an estimate of 0.48 for U_d
• this approximation of U_d is probably an underestimate
• because it does not consider mutations in intron and intergenic regions that can also have negative effects
• the fact that our sequence-based minimal estimate for U_d in C. elegans is about 30-fold higher than the estimate based on laboratory fitness assays indicates that most spontaneous mutations in C. elegans have very mildly deleterious effects that are realized only in natural contexts