SPECIAL ISSUE: DETECTING SELECTION IN NATURAL POPULATIONS: MAKING SENSE OF GENOME SCANS AND TOWARDS ALTERNATIVE SOLUTIONS Inferring the age of a fixed beneficial allele LOUISE ORMOND,* † MATTHIEU FOLL,* †‡ GREGORY B. EWING,* † SUSANNE P. PFEIFER* † and JEFFREY D. JENSEN* † *School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne, Switzerland, †Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland, ‡International Agency for Research on Cancer (IARC), Lyon, France Abstract Estimating the age and strength of beneficial alleles is central to understanding how adaptation proceeds in response to changing environmental conditions. Several haplo- type-based estimators exist for inferring the age of segregating beneficial mutations. Here, we develop an approximate Bayesian-based approach that rather estimates these parameters for fixed beneficial mutations in single populations. We integrate a range of existing diversity, site frequency spectrum, haplotype- and linkage disequilibrium- based summary statistics. We show that for strong selective sweeps on de novo muta- tions the method can estimate allele age and selection strength even in nonequilibrium demographic scenarios. We extend our approach to models of selection on standing variation, and co-infer the frequency at which selection began to act upon the muta- tion. Finally, we apply our method to estimate the age and selection strength of a pre- viously identified mutation underpinning cryptic colour adaptation in a wild deer mouse population, and compare our findings with previously published estimates as well as with geological data pertaining to the presumed shift in selective pressure. Keywords: adaptation, ecological genetics, population genetics – empirical, population genetics – theoretical Received 8 May 2015; revision received 14 October 2015; accepted 9 November 2015 Introduction Selective sweeps are believed to have played a role in shaping genomic patterns of variation across a wide range of species. Estimating the parameters underlying this process, including the beneficial allele age and asso- ciated selection strength, can provide deeper insights into the mode and tempo of adaptation. With regard to allele age in particular, one question that has remained of particular focus is whether specifically identified ben- eficial mutations correspond with the timing of an envi- ronmental change experienced by the population in question – be it the colonization of a novel habitat or a sudden geological event. This question is often posed in the context of whether adaptive events more commonly draw on new or standing genetic variation – and indeed, significant debate remains around this topic (Jensen 2014). Adaptation from new mutations may be said to be ‘mutation limited’, in that the appropriate mutation would need to occur after the shift in selective pressure. Thus, the ability to accurately infer the age and the starting frequency at the onset of selection of identified beneficial mutations relative to known envi- ronmental shifts will be key for advancing this debate. Many tests have been designed to identify the action of selection in the genome from patterns of polymor- phism (see review of Thornton et al. (2007); Bank et al. (2014)). These rely on frequency changes in linked neu- tral sites induced by a selective sweep, a process known as ‘genetic hitchhiking’ (Kaplan et al. 1989). Polymor- phism-based signals are relatively fleeting and are typi- cally visible only on a timescale of 0.1 N e generations or less, for an effective population size N e (Przeworski 2003). Yet the majority of approaches are intended to only identify beneficial fixations, and comparatively few approaches exist for inferring the age of these variants. Over the last few years, method development has lar- gely focused on time-sampled data sets, and much pro- gress has been made in this area (e.g. McVean 2002; Correspondence: Jeffrey D. Jensen, E-mail: jeffrey.jensen@epfl.ch © 2015 John Wiley & Sons Ltd Molecular Ecology (2015) doi: 10.1111/mec.13478