Dissecting the sequential evolution of a selfish mitochondrial genome in Caenorhabditis elegans data

Mitochondrial genomes exist in a nested hierarchy of populations where
mitochondrial variants are subject to genetic drift and selection at each
level of organization, sometimes engendering conflict between different
levels of selection, and between the nuclear and mitochondrial genomes.
Deletion mutants in the Caenorhabditis elegans mitochondrial genome can
reach high intracellular frequencies despite strongly detrimental effects
on fitness. During a mutation accumulation (MA) experiment in C. elegans,
a 499 bp deletion in ctb-1 rose to 90% frequency within cells while
significantly reducing fitness. During the experiment, the
deletion-bearing mtDNA acquired three additional mutations in nd5, namely
two single insertion frameshift mutations in a homopolymeric run, and a
base substitution. Despite an additional fitness cost of these secondary
mutations, all deletion-bearing molecules contained the nd5 mutations at
the termination of the MA experiment. The presence of mutant mtDNA was
associated with increased mtDNA copy-number. Variation in mtDNA
copy-number was greater in the MA lines than in a wildtype nuclear
background, including a severe reduction in copy-number at
one generational timepoint. Evolutionary replay experiments using
different generations of the MA experiment as starting points suggests
that two of the secondary mutations contribute to the proliferation of the
original ctb-1 deletion by unknown mechanisms.