Spontaneous Mutation Rates

There is a long-standing interest in the study of mutations—from the quest to enhance evolutionary inference related to the genetic underpinnings of disease, to the improvement of our understanding of the chronology of human evolution, to characterizing relationships between species. There is substantial uncertainty in historical estimates obtained from indirect methods: classical genetic approaches, going back to Haldane’s work in 1935 that utilized information from incidence of genetic disorders; and phylogenetic approaches, based on Kimura’s observation that under neutrality the mutation rate is equal to the rate of divergence. However, recent advances in high-throughput sequencing have made it possible to estimate mutation rates directly from parent-offspring trios and multigenerational pedigrees. Moreover, the combination of mutation accumulation studies with high-throughput sequencing has led to nearly complete, largely unbiased insights into the genome-wide spontaneous mutation rate in several experimentally tractable organisms. This chapter will focus on the basic concepts underlying the different methods used to estimate spontaneous mutation rates and will summarize current knowledge regarding the evolution of mutation rates across taxa.