SweepFinder is a popular program that implements a powerful likelihood-based method for detecting recent positive selection, or selective sweeps. Here, we present SweepFinder2, an extension of SweepFinder with increased sensitivity and robustness to
the confounding effects of mutation rate variation and background selection, as well as increased flexibility that enables the user to examine genomic regions in greater detail and to specify a fixed distance between test sites. Moreover, SweepFinder2 enables the use of invariant sites for sweep detection, increasing both its power and precision relative to SweepFinder.
While much effort has focused on detecting positive and negative directional selection in the human genome, relatively little work has been devoted to balancing selection. This lack of attention is likely due to the paucity of sophisticated methods f
or identifying sites under balancing selection. Here we develop two composite likelihood ratio tests for detecting balancing selection. Using simulations, we show that these methods outperform competing methods under a variety of assumptions and demographic models. We apply the new methods to whole-genome human data, and find a number of previously-identified loci with strong evidence of balancing selection, including several HLA genes. Additionally, we find evidence for many novel candidates, the strongest of which is FANK1, an imprinted gene that suppresses apoptosis, is expressed during meiosis in males, and displays marginal signs of segregation distortion. We hypothesize that balancing selection acts on this locus to stabilize the segregation distortion and negative fitness effects of the distorter allele. Thus, our methods are able to reproduce many previously-hypothesized signals of balancing selection, as well as discover novel interesting candidates.
