University of California, San Francisco

A biochemist looks at how DNA sequencing can reveal more than just sequences.

Huge advances in DNA sequencing have allowed us to readily determine the sequence of almost any living (and a few extinct) species. Yet arguably, most biological insight comes from work on five model organisms: Escherichia coli, baker's yeast, roundworms, fruitflies and mice. Unfortunately, many important biological processes are not captured in these creatures.

Papers from two groups, one led by Andrew Camilli of Tufts University in Boston, Massachusetts, the other by Brian Akerley at the University of Massachusetts in Worcester, describe new genetic tools that allow the quantitative dissection of gene function in a wide range of microorganisms (T. van Opijnen et al. Nature Methods 6, 767–772; 2009; and J. D. Gawronski et al. Proc. Natl Acad. Sci. USA 106, 16422–16427; 2009). These studies combine exhaustive transposon mutagenesis — whereby thousands of small DNA segments, or transposons, are introduced into the genome to mutate many genes — with massively parallel, or 'deep' sequencing of transposon/chromosome junctions to monitor the consequences of the loss of single or pairs of genes on the organisms' traits.

The real power of the approaches comes from the deep sequencing, which tracks the abundance of individual transposon mutants after they have been subjected to a stress. Knowing by how much each mutant has grown or suffered under the stress provides a measure of the relative roles that the mutated genes have.

I find it particularly gratifying that the advances in deep sequencing that have allowed us to catalogue so many genes from so many organisms can now be harnessed to help us figure out what these genes actually do.