Uninformative polymorphisms bias genome scans for signatures of selection

Marius Roesti,Walter Salzburger,Daniel Berner

doi:10.1186/1471-2148-12-94

Abstract

BackgroundWith the establishment of high-throughput sequencing technologies and new methods for rapid and extensive single nucleotide (SNP) discovery, marker-based genome scans in search of signatures of divergent selection between populations occupying ecologically distinct environments are becoming increasingly popular.Methods and ResultsOn the basis of genome-wide SNP marker data generated by RAD sequencing of lake and stream stickleback populations, we show that the outcome of such studies can be systematically biased if markers with a low minor allele frequency are included in the analysis. The reason is that these ‘uninformative’ polymorphisms lack the adequate potential to capture signatures of drift and hitchhiking, the focal processes in ecological genome scans. Bias associated with uninformative polymorphisms is not eliminated by just avoiding technical artifacts in the data (PCR and sequencing errors), as a high proportion of SNPs with a low minor allele frequency is a general biological feature of natural populations.ConclusionsWe suggest that uninformative markers should be excluded from genome scans based on empirical criteria derived from careful inspection of the data, and that these criteria should be reported explicitly. Together, this should increase the quality and comparability of genome scans, and hence promote our understanding of the processes driving genomic differentiation.

Highlights

With the establishment of high-throughput sequencing technologies and new methods for rapid and extensive single nucleotide (SNP) discovery, marker-based genome scans in search of signatures of divergent selection between populations occupying ecologically distinct environments are becoming increasingly popular
The number of single nucleotide polymorphisms (SNPs) dropped by 46.5% and 34% in the Constance and Boot system when singleton loci were excluded by setting n to two (Figure 2A)
The genomic location of these singleton loci did not show any systematic association with chromosome position

Summary

Introduction

With the establishment of high-throughput sequencing technologies and new methods for rapid and extensive single nucleotide (SNP) discovery, marker-based genome scans in search of signatures of divergent selection between populations occupying ecologically distinct environments are becoming increasingly popular. (Note that we here use divergent selection in a broad sense, including situations where an allele is selected in one environment but neutral in the other.) On the other hand, reference-based genome scans map loci physically to an available genome e.g., [15,16,17,18]. This offers a great advantage: loci occurring in the same genomic neighbourhood, and exhibiting some physical linkage, will tend to display correlated FST values that can be integrated by taking a sliding window approach. Depending on the marker resolution, outlier regions may be screened for candidate genes potentially targeted by divergent selection

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