title: Clear: Composition of Likelihoods for Evolve and Resequence Experiments.
abstract: The advent of next generation sequencing technologies has made whole-genome and whole-population sampling possible, even for eukaryotes with large genomes. With this development, experimental evolution studies can be designed to observe molecular evolution "in action" via evolve-and-resequence (E&R) experiments. Among other applications, E&R studies can be used to locate the genes and variants responsible for genetic adaptation. Most existing literature on time-series data analysis often assumes large population size, accurate allele frequency estimates, or wide time spans. These assumptions do not hold in many E&R studies. In this article, we propose a method-composition of likelihoods for evolve-and-resequence experiments (Clear)-to identify signatures of selection in small population E&R experiments. Clear takes whole-genome sequences of pools of individuals as input, and properly addresses heterogeneous ascertainment bias resulting from uneven coverage. Clear also provides unbiased estimates of model parameters, including population size, selection strength, and dominance, while being computationally efficient. Extensive simulations show that Clear achieves higher power in detecting and localizing selection over a wide range of parameters, and is robust to variation of coverage. We applied the Clear statistic to multiple E&R experiments, including data from a study of adaptation ofDrosophila melanogasterto alternating temperatures and a study of outcrossing yeast populations, and identified multiple regions under selection with genome-wide significance.
authors.affiliation: Department of Electrical and Computer Engineering, University of California, San Diego, California 92093 airanmehr@gmail.com.
authors.forename: Arya
authors.identifier: 0000-0002-8404-9797
authors.initials: A
authors.lastname: Iranmehr
authors.affiliation: Department of Electrical and Computer Engineering, University of California, San Diego, California 92093.
authors.forename: Ali
authors.identifier: 0000-0002-5000-5876
authors.initials: A
authors.lastname: Akbari
authors.affiliation: Institut für Populationsgenetik, Veterinärmedizinische Universität Wien, 1210 Vienna, Austria.
authors.forename: Christian
authors.identifier: 0000-0003-4710-6526
authors.initials: C
authors.lastname: Schlötterer
authors.affiliation: Department of Computer Science and Engineering, University of California, San Diego, California 92093.
authors.forename: Vineet
authors.initials: V
authors.lastname: Bafna
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D004331:Drosophila melanogaster / Q000235:genetics; D019143:Evolution, Molecular; D005787:Gene Frequency; D016678:Genome / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D011156:Population Density; D012641:Selection, Genetic
keywords: Wright–Fisher process; experimental evolution; genetic drift; hidden Markov model; selection; time-series data