A genome-wide view of Caenorhabditis elegans base-substitution mutation processes
- 22 September 2009
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 106 (38), 16310-16314
- https://doi.org/10.1073/pnas.0904895106
Abstract
Knowledge of mutation processes is central to understanding virtually all evolutionary phenomena and the underlying nature of genetic disorders and cancers. However, the limitations of standard molecular mutation detection methods have historically precluded a genome-wide understanding of mutation rates and spectra in the nuclear genomes of multicellular organisms. We applied two high-throughput DNA sequencing technologies to identify and characterize hundreds of spontaneously arising base-substitution mutations in 10 Caenorhabditis elegans mutation-accumulation (MA)-line nuclear genomes. C. elegans mutation rate estimates were similar to previous calculations based on smaller numbers of mutations. Mutations were distributed uniformly within and among chromosomes and were not associated with recombination rate variation in the MA lines, suggesting that intragenomic variation in genetic hitchhiking and/or background selection are primarily responsible for the chromosomal distribution patterns of polymorphic nucleotides in C. elegans natural populations. A strong mutational bias from G/C to A/T nucleotides was detected in the MA lines, implicating oxidative DNA damage as a major endogenous mutagenic force in C. elegans. The observed mutational bias also suggests that the C. elegans nuclear genome cannot be at equilibrium because of mutation alone. Transversions dominate the spectrum of spontaneous mutations observed here, whereas transitions dominate patterns of allegedly neutral polymorphism in natural populations of C. elegans and many other animal species; this observation challenges the assumption that natural patterns of molecular variation in noncoding regions of the nuclear genome accurately reflect underlying mutation processes.This publication has 36 references indexed in Scilit:
- A genomic bias for genotype–environment interactions in C. elegansMolecular Systems Biology, 2012
- Analysis of the genome sequences of three Drosophila melanogaster spontaneous mutation accumulation linesGenome Research, 2009
- Molecular Spectrum of Spontaneous de Novo Mutations in Male and Female Germline Cells of Drosophila melanogasterGenetics, 2009
- Estimation of Nucleotide Diversity, Disequilibrium Coefficients, and Mutation Rates from High-Coverage Genome-Sequencing ProjectsMolecular Biology and Evolution, 2008
- A genome-wide view of the spectrum of spontaneous mutations in yeastProceedings of the National Academy of Sciences of the United States of America, 2008
- TileQC: A system for tile-based quality control of Solexa dataBMC Bioinformatics, 2008
- Base-pairing properties of the oxidized cytosine derivative, 5-hydroxy uracilBiochemical and Biophysical Research Communications, 2008
- Transition-Transversion Bias Is Not Universal: A Counter Example from Grasshopper PseudogenesPLoS Genetics, 2007
- High mutation rate and predominance of insertions in the Caenorhabditis elegans nuclear genomeNature, 2004
- Patterns of nucleotide substitution in pseudogenes and functional genesJournal of Molecular Evolution, 1982