Denver C.elegans base-substitution mutation processes
A genome-wide view of Caenorhabditis elegans base-substitution mutation processes
10 C.elegans mutation-accumulation lines derived from the N2 progenitor are sequenced here using both 454 and Illumina sequencing technologies.
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 and spectrum 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 theMAlines, 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.