Research Highlights

The evolution of sequencing

Peter Keightley and his team at the University of Edinburgh have used high-throughput sequencing technology at the Gene Pool to estimate the background mutation rate in Drosophila melanogaster fruit flies (1).

Measuring the underlying mutation rate in organisms is essential to understanding their evolution. Evolution by natural selection acts on variation between individuals, and the ultimate source of that variation is mutation. So the mode and tempo of evolution depends on the rate at which new mutations arise. For example, knowing the rate at which spontaneous mutations occur in the absence of natural selection or environmental factors allows researchers to calculate when two species diverged, and can be used to uncover the effects of ongoing selection.

Using strains inbred over hundreds of generations to reduce the effect of natural selection, the group was able to sequence 60% of the Drosophila genome for rare mutations. They estimated the mutation rate to be 3.5x10-9 per site per generation, similar to earlier estimates of the same lines based on traditional sequencing methods. However, this rate was significantly different from estimates on other known inbred strains (2), suggesting substantial spontaneous mutation rate variation in Drosophila.

Past studies of Drosophila mutation rate were restricted to very small proportions of the genome, in part due to the limitations of DNA sequencing and mutation detection technology. But the new high-throughput technology provided by the Gene Pool, a SULSA-supported facility, allowed the authors to compare most of the genome, providing a more accurate result free of biases due to target selection.

Moving forward

The authors have demonstrated the power of high-throughput DNA sequencing technology for more accurate measurement of background mutation rates. In future, this power can be harnessed to allow sequencing of parents and offspring directly. This would remove the need for inbred lines, as the ability to detect extremely rare mutations would allow genome analysis without accumulation of mutations over many generations. This sequencing technology will also allow analysis of mutation rates in organisms with long generation times, opening up new possibilities in the study of evolution and in the identification of spontaneous mutations underpinning disease.

Melanie Lawrence, Melanie.Lawrence@hgu.mrc.ac.uk

1. Keightley PD, Trivedi U, Thomson M, Oliver F, Kumar S and Blaxter ML, 2009. Genome Research 19, 1195-1201
2. Haag-Liautard C, Dorris M, Maside X, Macaskill S, Halligan DL, Houle D, Chalesworth B, Keightley PD, 2007. Nature 445, 82-85