Compensating for deleterious mutations

Fitness recovery and compensatory evolution in natural mutant lines of C.
Elegans.
By Estes S, Phillips PC, Denver DR.
Evolution. 2011 Aug;65(8):2335-44. doi: 10.1111/j.1558-5646.2011.01276.x. Epub
2011 Apr 11.
Abstract
Deleterious mutation accumulation plays a central role in evolutionary genetics, 
conservation biology, human health, and evolutionary medicine (e.g., methods of
viral attenuation for live vaccines). It is therefore important to understand
whether and how quickly populations with accumulated deleterious mutational loads
can recover fitness through adaptive evolution. We used laboratory experimental
evolution with four long-term mutation-accumulation (MA) lines of Caenorhabditis 
elegans nematodes to study the dynamics of such fitness evolution. We previously 
showed that when homozygous mutant populations are evolved in large population
sizes, they can rapidly achieve wild-type fitness through the accumulation of new
beneficial or compensatory epistatic mutations. Here, we expand this approach to 
demonstrate that when replicate lineages are initiated from the same mutant
genotype, phenotypic evolution is only sometimes repeatable. MA genotypes that
recovered ancestral fitness in the previous experiment did not always do so here.
Further, the pattern of adaptive evolution in independently evolved replicates
was contingent upon the MA genotype and varied among fitness-related traits. Our 
findings suggest that new beneficial mutations can drive rapid fitness evolution,
but that the adaptive process is rendered somewhat unpredictable by its
susceptibility to chance events and sensitivity to the evolutionary history of
the starting population.