Short-read sequencing techniques provide the opportunity to capture genome-wide sequence data in a single experiment. A current challenge is to identify questions that shallow-depth genomic data can address successfully and to develop corresponding analytical methods that are statistically sound. Here, we apply the Roche/454 platform to survey natural variation in strains of Drosophila melanogaster from an African (n = 3) and a North American (n = 6) population. Reads were aligned to the reference D. melanogaster genomic assembly, single nucleotide polymorphisms were identified, and nucleotide variation was quantified genome wide. Simulations and empirical results suggest that nucleotide diversity can be accurately estimated from sparse data with as little as 0.2x coverage per line. The unbiased genomic sampling provided by random short-read sequencing also allows insight into distributions of transposable elements and copy number polymorphisms found within populations and demonstrates that short-read sequencing methods provide an efficient means to quantify variation in genome organization and content. Continued development of methods for statistical inference of shallow-depth genome-wide sequencing data will allow such sparse, partial data sets to become the norm in the emerging field of population genomics.
Sackton, Timothy BKulathinal, Rob JBergman, Casey MQuinlan, Aaron RDopman, Erik BCarneiro, MauricioMarth, Gabor THartl, Daniel LClark, Andrew GengR01 AI064950/AI/NIAID NIH HHS/R01 AI064950-04/AI/NIAID NIH HHS/R01 HG004719/HG/NHGRI NIH HHS/R01 HG004719-01/HG/NHGRI NIH HHS/R01 HG004719-02/HG/NHGRI NIH HHS/R01 HG004719-02S1/HG/NHGRI NIH HHS/R01 HG004719-03/HG/NHGRI NIH HHS/R01 HG004719-04/HG/NHGRI NIH HHS/England2009/01/01 00:00Genome Biol Evol. 2009 Nov 18;1:449-65. doi: 10.1093/gbe/evp048.