Natural Selection in the Great Apes

Natural Selection in the Great Apes Alexander Cagan,†,1 Christoph Theunert,†,1,2 Hafid Laayouni,†,3,4 Gabriel Santpere,†,3,5 Marc Pybus,3 Ferran Casals,6 Kay Prüfer,1 Arcadi Navarro,3,7 Tomas Marques-Bonet,3,7 Jaume Bertranpetit,‡,3,8 and Aida M. Andrés*,‡,1 1 Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany Department of Integrative Biology, University of California, Berkeley, Berkeley, CA 3 Departament de Ciencies Experimentals i de la Salut, Institut de Biologia Evolutiva, Universitat Pompeu Fabra, Barcelona, Catalonia, Spain 4 Departament de Genètica i de Microbiologia, Universitat Autonoma de Barcelona, Bellaterra, Barcelona, Catalonia, Spain 5 Department of Neuroscience, Yale University School of Medicine, New Haven, CT 6 Genomics Core Facility, Departament de Ciencies Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Catalonia, Spain 7 Instituci o Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain 8 Department of Archaeology and Anthropology, Leverhulme Centre for Human Evolutionary Studies, University of Cambridge, Cambridge, United Kingdom † These authors contributed equally to this work. ‡ These authors equally co-supervised this work. *Corresponding author: E-mail: . Associate editor: Ryan Hernandez 2 Article Natural selection is crucial for the adaptation of populations to their environments. Here, we present the first global study of natural selection in the Hominidae (humans and great apes) based on genome-wide information from population samples representing all extant species (including most subspecies). Combining several neutrality tests we create a multi-species map of signatures of natural selection covering all major types of natural selection. We find that the estimated efficiency of both purifying and positive selection varies between species and is significantly correlated with their long-term effective population size. Thus, even the modest differences in population size among the closely related Hominidae lineages have resulted in differences in their ability to remove deleterious alleles and to adapt to changing environments. Most signatures of balancing and positive selection are species-specific, with signatures of balancing selection more often being shared among species. We also identify loci with evidence of positive selection across several lineages. Notably, we detect signatures of positive selection in several genes related to brain function, anatomy, diet and immune processes. Our results contribute to a better understanding of human evolution by putting the evidence of natural selection in humans within its larger evolutionary context. The global map of natural selection in our closest living relatives is available as an interactive browser at http://tinyurl.com/nf8qmzh. Key words: evolution, adaptation, comparative genomics, primates. Introduction Understanding the adaptive genetic changes that led to the emergence of modern humans continues to be a major focus of modern genomics (Pritchard et al. 2010; Enard et al. 2014). However, despite much work in this field, many central questions remain unanswered. For example, it is still unclear what percentage of the human genome has been shaped by natural selection, which genetic variants are responsible for the phenotypes that make humans unique, and to what extent demographic factors have influenced the rate of adaptive evolution through human history. These questions can only be answered through a deeper understanding of the evolution both of the human genome and also of other closely related species. While laboratory studies on adaptation in organisms such as Drosophila have furthered our understanding of adaptive evolution (Lee et al. 2014), the usefulness of these model organisms for understanding adaptation in humans is limited by the wide disparities that exist between them and humans, in both physiology and demography. Investigation of the molecular basis of adaptation is also hindered by differences in the structure and content of the genomes of more distantly related organisms. Studying our closest living relatives, the great apes, is therefore crucial for furthering our understanding of human evolution. The Hominidae (humans and great apes) share several traits that make them particularly interesting. Relative to their ancestors they have evolved larger brains, more complex social systems and, arguably, the ability to create and maintain cultural traditions (McGrew 2004). Furthermore, the Hominidae species differ from one another in important ways (including their morphology, physiology, behavior and ß The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact 3268 Open Access Mol. Biol. Evol. 33(12):3268–3283 doi:10.1093/molbev/msw215 Abstract MBE Natural Selection in the Great Apes . doi:10.1093/molbev/msw215 Results Sample Processing In order to assess the influence of natural selection, we use a dataset of 54 non-human great ape and nine human genomes sequenced to an average of 25-fold coverage (supplementary table S1, Supplementary Material online). Because of differences in demography and selective pressures on autosomes and sex chromosomes, we focus exclusively on the autosomes. We take particular care to minimize the influence of errors and biases in genomic data and ensure that our data is of the highest possible quality—something particularly important when comparing species. All reads were mapped to the same reference genome (human hg18). We built on the extensive data filtering strategy of Prado-Martinez et al. (2013) (see “Dataset” in “Methods” section). This conservative filtering strategy resulted in the exclusion of 726 Mb (23%) of the autosomal genome. This includes tandem repeats (38 Mb), segmental duplications (154 Mb) and structural variants annotated in at least one species (334 Mb) (see supplemen tary fig. S1, Supplementary Material online), all identified by unusual read-depth, so alternative methods (Gokcumen et al. 2013; Sudmant et al. 2015) may identify nonidentical regions. While certain genomic regions and gene families may be enriched in structural variation and be disproportionately affected by this filtering step, their removal is essential to minimize artifacts. We also excluded genomic gaps (226 Mb) and base pairs that were not covered by a minimum of five reads in all individuals per species. The resulting dataset includes on an average 2,099 Mb of analyzable genome sequence per species (see supplementary fig. S1, Supplementary Mater (...truncated)