Direct estimation of the mitochondrial DNA mutation rate in Drosophila melanogaster

Cathy Haag-Liautard, Nicole Coffey, David Houle, Michael Lynch, Brian Charlesworth, Peter D. Keightley

Research output: Contribution to journalArticle

165 Citations (Scopus)

Abstract

Mitochondrial DNA (mtDNA) variants are widely used in evolutionary genetics as markers for population history and to estimate divergence times among taxa. Inferences of species history are generally based on phylogenetic comparisons, which assume that molecular evolution is clock-like. Between-species comparisons have also been used to estimate the mutation rate, using sites that are thought to evolve neutrally. We directly estimated the mtDNA mutation rate by scanning the mitochondrial genome of Drosophila melanogaster lines that had undergone approximately 200 generations of spontaneous mutation accumulation (MA). We detected a total of 28 point mutations and eight insertion-deletion (indel) mutations, yielding an estimate for the single-nucleotide mutation rate of 6.2 × 10-8 per site per fly generation. Most mutations were heteroplasmic within a line, and their frequency distribution suggests that the effective number of mitochondrial genomes transmitted per female per generation is about 30. We observed repeated occurrences of some indel mutations, suggesting that indel mutational hotspots are common. Among the point mutations, there is a large excess of G→A mutations on the major strand (the sense strand for the majority of mitochondrial genes). These mutations tend to occur at nonsynonymous sites of protein-coding genes, and they are expected to be deleterious, so do not become fixed between species. The overall mtDNA mutation rate per base pair per fly generation in Drosophila is estimated to be about 10X higher than the nuclear mutation rate, but the mitochondrial major strand G→A mutation rate is about 70X higher than the nuclear rate. Silent sites are substantially more strongly biased towards A and T than nonsynonymous sites, consistent with the extreme mutation bias towards A+T. Strand-asymmetric mutation bias, coupled with selection to maintain specific nonsynonymous bases, therefore provides an explanation for the extreme base composition of the mitochondrial genome of Drosophila.

Original languageEnglish (US)
Article numbere204
Pages (from-to)1706-1714
Number of pages9
JournalPLoS Biology
Volume6
Issue number8
DOIs
StatePublished - Aug 1 2008
Externally publishedYes

Fingerprint

Mutation Rate
Drosophila melanogaster
Mitochondrial DNA
mitochondrial DNA
Genes
mutation
Mitochondrial Genome
Mutation
INDEL Mutation
Point Mutation
Diptera
Drosophila
Mitochondrial Genes
Molecular Evolution
Base Composition
point mutation
Clocks
Genetic Markers
Base Pairing
Nucleotides

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Haag-Liautard, C., Coffey, N., Houle, D., Lynch, M., Charlesworth, B., & Keightley, P. D. (2008). Direct estimation of the mitochondrial DNA mutation rate in Drosophila melanogaster. PLoS Biology, 6(8), 1706-1714. [e204]. https://doi.org/10.1371/journal.pbio.0060204

Direct estimation of the mitochondrial DNA mutation rate in Drosophila melanogaster. / Haag-Liautard, Cathy; Coffey, Nicole; Houle, David; Lynch, Michael; Charlesworth, Brian; Keightley, Peter D.

In: PLoS Biology, Vol. 6, No. 8, e204, 01.08.2008, p. 1706-1714.

Research output: Contribution to journalArticle

Haag-Liautard, C, Coffey, N, Houle, D, Lynch, M, Charlesworth, B & Keightley, PD 2008, 'Direct estimation of the mitochondrial DNA mutation rate in Drosophila melanogaster', PLoS Biology, vol. 6, no. 8, e204, pp. 1706-1714. https://doi.org/10.1371/journal.pbio.0060204
Haag-Liautard C, Coffey N, Houle D, Lynch M, Charlesworth B, Keightley PD. Direct estimation of the mitochondrial DNA mutation rate in Drosophila melanogaster. PLoS Biology. 2008 Aug 1;6(8):1706-1714. e204. https://doi.org/10.1371/journal.pbio.0060204
Haag-Liautard, Cathy ; Coffey, Nicole ; Houle, David ; Lynch, Michael ; Charlesworth, Brian ; Keightley, Peter D. / Direct estimation of the mitochondrial DNA mutation rate in Drosophila melanogaster. In: PLoS Biology. 2008 ; Vol. 6, No. 8. pp. 1706-1714.
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