Justin B. Lack*,¹, Charis M. Cardeno^†, Marc W. Crepeau^†, William Taylor^‡, Russell B. Corbett-Detig^§,**, Kristian A. Stevens^†, Charles H. Langley^†,¹ and John E. Pool*,¹

GENETICS April 1, 2015 vol. 199 no. 4 1229-1241

http://www.genetics.org/content/199/4/1229.abstract?etoc

Abstract

Hundreds of wild-derived Drosophila melanogaster genomes have been published, but rigorous comparisons across data sets are precluded by differences in alignment methodology. The most common approach to reference-based genome assembly is a single round of alignment followed by quality filtering and variant detection. We evaluated variations and extensions of this approach and settled on an assembly strategy that utilizes two alignment programs and incorporates both substitutions and short indels to construct an updated reference for a second round of mapping prior to final variant detection. Utilizing this approach, we reassembled published D. melanogaster population genomic data sets and added unpublished genomes from several sub-Saharan populations. Most notably, we present aligned data from phase 3 of the Drosophila Population Genomics Project (DPGP3), which provides 197 genomes from a single ancestral range population of D. melanogaster (from Zambia). The large sample size, high genetic diversity, and potentially simpler demographic history of the DPGP3 sample will make this a highly valuable resource for fundamental population genetic research. The complete set of assemblies described here, termed the Drosophila Genome Nexus, presently comprises 623 consistently aligned genomes and is publicly available in multiple formats with supporting documentation and bioinformatic tools. This resource will greatly facilitate population genomic analysis in this model species by reducing the methodological differences between data sets.

Figure 1

Comparison of genomic coverage and error rate for various genome assembly pipeline variations, based on resequencing of the D. melanogaster reference. (A) Heat maps illustrating variation in coverage (left) and error rate (right) at the Q75 threshold chosen to optimize the trade-off between coverage and error rate. (B) Evaluation of the trade-off between genomic coverage and error rate for the haploid caller of the Unified Genotyper; quality values ranged from 10 to 100. Resequenced genomes from the reference strain (y¹ cn¹ bw¹ sp¹) were modified to simulate realistic levels of variation. We chose a cutoff of Q75 (red) to maximize coverage and minimize error.