deleterious mutation - senecio7の日記

Keightley PD & Eyre-Walker A 1999 Terumi Mukai and the riddle of deleterious mutation rates. Genetics 153:515-523.

one approach to estimating the mutation rate to deleterious, but nonlethal, mutations is to use information on the rate at which visible mutations arise
for loci that generate visible mutations in Drosophila, rates typically run around 10⁻⁵ (Drake et al. 1998)
assuming that D. melanogaster contains 15,000 loci, this translates to a genome-wide mutation rate of 0.15 per haploid
some 15-fold higher than the lethal rate
paradoxically, however, mutations with visible effects occur much less frequently than lethals in genome-wide surveys (Muller 1950)
the likely explanation is that genes used in assays for visible phenotypes have mutation rates higher than those of other genes, for a variety of reasons
furthermore, many deleterious mutations do not have visible effects

some of the apparent decline in fitness of the quasinormal lines in Mukai and Ohnishi's experiments might be nonmutational in origin
the most plausible nonmutational explanation for Mukai and Ohnishi's results comes from a later Drosophila MA experiment involving Cy/Pm
Fry et al. (1999) observed that Cy expression is variable
heterozygotes may be distinguished from wild types only if an additional chromosome 2 marker is present
if the ability of an experimentalist to recognize weak Cy expression improved over time, the relative viability of wild-type chromosomes would appear to decline over time

there has recently been renewed interest in inferring rates and effects of deleterious mutations
the longest-running published MA experiment in a eukaryote has been reported by Fernandez and Lopez-Fanjul (1996)
mean egg-to-adult viability (measured under noncompetitive conditions) declined relative to the control at a rate of only about 0.1% per generation (Garcia-Dorado 1997)
Bateman estimates of U (per haploid genome) and s are ~0.02 and ~0.10, respectively (Garcia-Dorado et al. 1999)
the estimate for U is, therefore, more than 10-fold lower than those obtained by Mukai and Ohnishi (Table 1)

Fry et al. (1999) have reported the results from a chromosome 2 MA experiment in Drosophila carried out over 27-33 generations with a design similar to Mukai and Ohnishi's
in addition they performed parallel assays of three control populations maintained at large effective size
resulting Bateman estimates of U (extrapolated to the whole haploid genome) and s are 0.05 and 0.11, respectively

are the estimates of U given by Mukai and colleagues correct?
it is possible that they are, but for wrong reasons
Mukai and colleagues probably did overestimate the mutation rate to mutations of moderate effect (i.e., the mutations detected in an MA experiment)
or there was exceptional TE activity in Mukai's lines
the band-morph and molecular divergence estimates are underestimates because they do not include mutations outside coding regions or mutations caused by TEs
the deleterious mutation rate caused by point mutations in Drosophila is likely to be ~0.1
the original estimates of U ≥ 0.5 and s ≤ 3% given by Mukai have been extensively cited and used by geneticists
they may have only very limited application