Genetic adaptation to external stimuli occurs through the combined action of mutation and selection. A central problem in genetics is to identify loci responsive to specific selective constraints. Many tests have been proposed to identify the genomic signatures of natural selection by quantifying the skew in the the site frequency spectrum (SFS) under selection relative to neutrality. We build upon recent work that connects many of these tests under a common framework, by describing how selective sweeps impact the scaled SFS (and cross-population SFS). We show that the specific skew depends on many attributes of the sweep, including the selection coefficient and the time under selection. Using supervised learning on extensive simulated data, we characterize the features of the scaled SFS that best separate different types of selective sweeps from neutrality. We develop a test, SFselect, that consistently outperforms many existing tests over a wide range of selective sweeps. Applying SFselect to variation data from a laboratory evolution experiment of Drosophila melanogaster adapted to hypoxia, we identify loci that strengthen the role of the Notch pathway in hypoxia tolerance, but were missed with previous approaches. Finally, we discuss the challenges and possibilities of learning to identify soft selection (e.g. on the standing variation) and distinguish it from classic hard selective sweeps.
Roy Ronen is a PhD candidate in the Bioinformatics and Systems Biology program at University of California, San Diego. He works with Dr. Vineet Bafna on the application of statistical learning and discrete algorithms to population genetics. Before this, he completed his undergraduate degree in computer science at Ben-Gurion University in Israel, and worked at Tel Aviv University’s high-throughput sequencing facility as a software developer. Roy is interested in the theory and application of methods for identifying mechanism of genetic adaptation.
Monday Jan 27th, 2014
12:45 PM Lunch: sign up sheet here. Come early for lunch, because we cannot take food into the seminar room!
1:15 PM Seminar starts.
Location: Munzer Hall (after Li Ka Shing on the medical campus)
Host: Carlos Bustamante
Schedule: Rosario Monge (rmonge at stanford.edu)