Uninformative polymorphisms bias genome scans for signatures of selection

BACKGROUND: 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. METHODS AND RESULTS: On 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. CONCLUSIONS: We 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.