title: Muller's Ratchet and compensatory mutation in Caenorhabditis briggsae mitochondrial genome evolution.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Zoology and Center for Genome Research and Biocomputing, Oregon State University, Corvallis, Oregon, 97331, USA. howed@science.oregonstate.edu
authors.forename: Dana K
authors.initials: DK
authors.lastname: Howe
authors.forename: Dee R
authors.initials: DR
authors.lastname: Denver
mesh_terms: D000818:Animals; D005075:Biological Evolution; D002107:Caenorhabditis / Q000235:genetics* / Q000502:physiology; D018509:DNA, Helminth / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics; D017353:Gene Deletion; D049751:Genome, Helminth; D054629:Genome, Mitochondrial; D008957:Models, Genetic; D009154:Mutation; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D012100:Reproduction, Asexual; D017422:Sequence Analysis, DNA
chemical_list: D018509:DNA, Helminth; D004272:DNA, Mitochondrial