Detecting recent selective sweeps while controlling for mutation rate and background selection.
A composite likelihood ratio test implemented in the program sweepfinder is a commonly used method for scanning a genome for recent selective sweeps. sweepfinder uses information on the spatial pattern (along the chromosome) of the site frequency spectrum around the selected locus. To avoid confounding effects of background selection and variation in the mutation process along the genome, the method is typically applied only to sites that are variable within species. However, the power to detect and localize selective sweeps can be greatly improved if invariable sites are also included in the analysis. In the spirit of a Hudson-Kreitman-Aguadé test, we suggest adding fixed differences relative to an out-group to account for variation in mutation rate, thereby facilitating more robust and powerful analyses. We also develop a method for including background selection, modelled as a local reduction in the effective population size. Using simulations, we show that these advances lead to a gain in power while maintaining robustness to mutation rate variation. Furthermore, the new method also provides more precise localization of the causative mutation than methods using the spatial pattern of segregating sites alone.
Max F. Perutz Laboratory, University of Vienna, Vienna, Austria.|Vienna Graduate School of Population Genetics, University of Veterinary Medicine, Vienna, Austria.|Department of Ecology and Evolutionary Biology, University of California, Los Angeles, 621 Charles E. Young Drive South, Los Angeles, CA, 90095-1606, USA.
Christian D
CD
Huber
Departments of Biology and Statistics, Pennsylvania State University, University Park, PA, USA.|Institute for CyberScience, Pennsylvania State University, University Park, PA, USA.
Michael
M
DeGiorgio
Department Biologie II, Ludwig-Maximilians-Universität München, Großhaderner Str. 2, 82152, Planegg-Martinsried, Germany.
Ines
I
Hellmann
Departments of Integrative Biology and Statistics, University of California, Berkeley, CA, USA.
Rasmus
R
Nielsen
D005787:Gene Frequency; D005828:Genetics, Population; D006801:Humans; D008957:Models, Genetic; D059645:Mutation Rate; D012641:Selection, Genetic
Hudson-Kreitman-Aguadé test; background selection; population bottlenecks; sweep detection; sweepfinder