deleterious mutation - senecio7の日記

Manna F, Gallet R, Martin G & Lenormand T 2012 The high-throughput yeast deletion fitness data and the theories of dominance. J Evol Biol 25:892-903.

the data on deletion of small effects are not sufficiently reliable to be informative on this question
deletions of large effect exhibit no correlation between homo- and heterozygous fitness effects, a pattern that sheds new light on the h-s correlation issue

the mean heterozygous fitness effect of lethal and nonlethal mutations has even been shown to be very similar in Drosophila (Simmons & Crow, 1977) and yeast (Szafraniec et al., 2003)

because the dominance of individual mutations is traditionally defined as a ratio, it has very poor mathematical and statistical properties

regression slopes were extremely variable among environments or between replicates
it ranges from negative (− 0.15 in YPG medium) to positive (+ 1.02 in YPL)
the slope of this regression is a measure of average dominance
these results impede any general conclusion to be drawn regarding dominance
they are also at odds with most previous findings regarding the dominance of mildly deleterious mutations (Manna et al., 2011 and references therein), which lies in the range 0.2–0.3

regression slopes of hetero- vs. homozygous effects are nearly zero within large-effect deletions
in contrast with the variable findings within small-effect deletions, this pattern is consistent across replicates and environments
within deletions of large effects, the heterozygous fitness effect is constant on average and does not increase when the homozygous effect increases
this pattern is very similar to the finding that lethal and nonlethal mutations have on average the same heterozygous effect

for mutations of large effect, it is certainly simpler to say that the average heterozygous effect of deletions is constant with increased homozygous effect than to assume a complex h-s relationship that exactly cancels out to lead to this simple pattern

most data form a dense correlated cloud that could be compatible with constant dominance, and the remaining deletions exhibit uncorrelated homozygous and heterozygous effects, a pattern qualitatively consistent with models presented in Manna et al. (2011)
an equally nice description is that there are two classes of mutations:
one with small effects and constant dominance
another with larger effects and constant heterozygous effect
the latter class would also include lethals that are known to exhibit similar heterozygous effects than the bulk of nonlethal mutations