BACKGROUND: The theory of Muller' Ratchet predicts that small asexual 
populations are doomed to accumulate ever-increasing deleterious mutation loads 
as a consequence of the magnified power of genetic drift and mutation that 
accompanies small population size. Evidence for Muller's Ratchet and knowledge 
on its underlying molecular mechanisms, however, are lacking for natural 
populations.
RESULTS: We characterized mitochondrial genome evolutionary processes in 
Caenorhabditis briggsae natural isolates to show that numerous lineages 
experience a high incidence of nonsynonymous substitutions in protein-coding 
genes and accumulate unusual deleterious noncoding DNA stretches with associated 
heteroplasmic function-disrupting genome deletions. Isolate-specific deletion 
proportions correlated negatively with nematode fecundity, suggesting that these 
deletions might negatively affect C. briggsae fitness. However, putative 
compensatory mutations were also observed that are predicted to reduce 
heteroplasmy levels of deleterious deletions. Paradoxically, compensatory 
mutations were observed in one major intraspecific C. briggsae clade where 
population sizes are estimated to be very small (and selection is predicted to 
be relatively weak), but not in a second major clade where population size 
estimates are much larger and selection is expected to be more efficient.
CONCLUSION: This study provides evidence that the mitochondrial genomes of 
animals evolving in nature are susceptible to Muller's Ratchet, suggests that 
context-dependent compensatory mutations can accumulate in small populations, 
and predicts that Muller's Ratchet can affect fundamental evolutionary forces 
such as the rate of mutation.