title: Mitochondrial Mutation Rate, Spectrum and Heteroplasmy in Caenorhabditis elegans Spontaneous Mutation Accumulation Lines of Differing Population Size.
abstract: Mitochondrial genomes of metazoans, given their elevated rates of evolution, have served as pivotal markers for phylogeographic studies and recent phylogenetic events. In order to determine the dynamics of spontaneous mitochondrial mutations in small populations in the absence and presence of selection, we evolved mutation accumulation (MA) lines of Caenorhabditis elegans in parallel over 409 consecutive generations at three varying population sizes of N = 1, 10, and 100 hermaphrodites. The N =1 populations should have a minimal influence of natural selection to provide the spontaneous mutation rate and the expected rate of neutral evolution, whereas larger population sizes should experience increasing intensity of selection. New mutations were identified by Illumina paired-end sequencing of 86 mtDNA genomes across 35 experimental lines and compared with published genomes of natural isolates. The spontaneous mitochondrial mutation rate was estimated at 1.05 × 10-7/site/generation. A strong G/C→A/T mutational bias was observed in both the MA lines and the natural isolates. This suggests that the low G + C content at synonymous sites is the product of mutation bias rather than selection as previously proposed. The mitochondrial effective population size per worm generation was estimated to be 62. Although it was previously concluded that heteroplasmy was rare in C. elegans, the vast majority of mutations in this study were heteroplasmic despite an experimental regime exceeding 400 generations. The frequencies of frameshift and nonsynonymous mutations were negatively correlated with population size, which suggests their deleterious effects on fitness and a potent role for selection in their eradication.
authors.affiliation: Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX.
authors.forename: Anke
authors.initials: A
authors.lastname: Konrad
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA.
authors.forename: Owen
authors.initials: O
authors.lastname: Thompson
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Waterston
authors.affiliation: Department of Zoology and Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Donald G
authors.initials: DG
authors.lastname: Moerman
authors.affiliation: Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Keightley
authors.affiliation: Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX.
authors.forename: Ulfar
authors.initials: U
authors.lastname: Bergthorsson
authors.affiliation: Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX.
authors.forename: Vaishali
authors.initials: V
authors.lastname: Katju
mesh_terms: D000818:Animals; D005075:Biological Evolution; D017173:Caenorhabditis elegans / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics; D019143:Evolution, Molecular; D054629:Genome, Mitochondrial / Q000235:genetics*; D008928:Mitochondria / Q000235:genetics; D009154:Mutation; D000067552:Mutation Accumulation; D059645:Mutation Rate; D010802:Phylogeny; D058974:Phylogeography; D011156:Population Density; D012641:Selection, Genetic / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods
chemical_list: D004272:DNA, Mitochondrial
keywords: Caenorhabditis elegans; genetic drift; heteroplasmy; mitochondria; mitochondrial effective population size; mutation rate; selection; spontaneous mutation