Identification of Selective Sweeps Using a Dynamically Adjusted Number of Linked Microsatellites

Abstract

There is currently large interest in distinguishing the signatures of genetic variation produced by demographic events from those produced by natural selection. We propose a simple multilocus statistical test to identify candidate sites of selective sweeps with high power. The test is based on the variability profile measured in an array of linked microsatellites. We also show that the analysis of flanking markers drastically reduces the number of false positives among the candidates that are identified in a genomewide survey of unlinked loci and find that this property is maintained in many populationbottleneck scenarios. However, for a certain range of intermediately severe population bottlenecks we find genomic signatures that are very similar to those produced by a selective sweep. While in these worst-case scenarios the power of the proposed test remains high, the false-positive rate reaches values close to 50%. Hence, selective sweeps may be hard to identify even if multiple linked loci are analyzed. Nevertheless, the integration of information from multiple linked loci always leads to a considerable reduction of the falsepositive rate compared to a genome scan of unlinked loci. We discuss the application of this test to experimental data from Drosophila melanogaster.

Hitchhiking Mapping Reveals a Candidate Genomic Region for Natural Selection in Three-Spined Stickleback Chromosome VIII

“…These caveats can be avoided by screening a large number of markers spaced across an organism's whole genome to characterize the background levels of marker variability and differentiation (Schlö tterer 2003). Second, as the analysis of genome scan data involves multiple statistical tests, identification of false-positive footprints of selection may become an issue (Wiehe et al 2007). One way to alleviate this particular problem is to genotype more loci in the genomic regions near a candidate locus.…”

“…One way to alleviate this particular problem is to genotype more loci in the genomic regions near a candidate locus. It is unlikely that a signature of selection emerging from a particular genomic region is false if it is detected in more than one marker locus (Wiehe et al 2007). However, while the analysis of markers flanking genomic regions of the candidate locus does not completely rule out demographic explanations, it is expected to result in a considerable reduction in the number of false positives (Thornton and Jensen 2007;Wiehe et al 2007).…”

“…It is unlikely that a signature of selection emerging from a particular genomic region is false if it is detected in more than one marker locus (Wiehe et al 2007). However, while the analysis of markers flanking genomic regions of the candidate locus does not completely rule out demographic explanations, it is expected to result in a considerable reduction in the number of false positives (Thornton and Jensen 2007;Wiehe et al 2007). Conducting this type of fine-scale analyses at the genomic level is becoming more feasible due to the increased availability of the whole-genome sequences for various organisms in recent years (Benson et al 2007;Storz and Hoekstra 2007).…”

“…This kind of analysis can identify loci showing footprints of natural selection and provide a starting point for a finer-scale analysis around these candidate loci. The adjacent marker loci can provide further proof of selection in a particular genomic region, but can also help to narrow down the genomic interval at which selection is operating (Wiehe et al 2007). Previous studies suggest that this approach might be useful in identifying genes involved in domestication, artificial selection, or in resistance to a drug treatment (Kohn et al 2000;Nair et al 2003;DuMont and Aquadro 2005;Olsen et al 2006;Pool et al 2006;Sutter et al 2007).…”

Second-Order Moments of Segregating Sites Under Variable Population Size

“…The reasoning here is that the traces of selective sweeps may be distinguished from those of recent population bottlenecks, since only the former have a local effect, while the latter should have a chromosomewide effect. In a test tailored for multiple microsatellite loci, Wiehe et al (2007) found that this is often the case, but, for a certain (population genetically relevant) range of demographic parameters the false positive rate to detect selective sweeps is still unacceptably high. Other recently popularized methods to detect traces of selection are centered around the analysis of linkage disequilibrium (Kim and Nielsen 2004;Stephan et al 2006;McVean 2007) or the structure and frequency spectrum of haplotypes (Sabeti et al 2002(Sabeti et al , 2007.…”