title: Human genome variation and the concept of genotype networks.
abstract: Genotype networks are a concept used in systems biology to study sets of genotypes having the same phenotype, and the ability of these to bring forth novel phenotypes. In the past they have been applied to determine the genetic heterogeneity, and stability to mutations, of systems such as metabolic networks and RNA folds. Recently, they have been the base for reconciling the neutralist and selectionist views on evolution. Here, we adapted this concept to the study of population genetics data. Specifically, we applied genotype networks to the human 1000 genomes dataset, and analyzed networks composed of short haplotypes of Single Nucleotide Variants (SNV). The result is a scan of how properties related to genetic heterogeneity and stability to mutations are distributed along the human genome. We found that genes involved in acquired immunity, such as some HLA and MHC genes, tend to have the most heterogeneous and connected networks, and that coding regions tend to be more heterogeneous and stable to mutations than non-coding regions. We also found, using coalescent simulations, that regions under selection have more extended and connected networks. The application of the concept of genotype networks can provide a new opportunity to understand the evolutionary processes that shaped our genome. Learning how the genotype space of each region of our genome has been explored during the evolutionary history of the human species can lead to a better understanding on how selective pressures and neutral factors have shaped genetic diversity within populations and among individuals. Combined with the availability of larger datasets of sequencing data, genotype networks represent a new approach to the study of human genetic diversity that looks to the whole genome, and goes beyond the classical division between selection and neutrality methods.
authors.affiliation: Institut de Biologia Evolutiva, CSIC-Universitat Pompeu Fabra, Barcelona, Catalonia, Spain.
authors.forename: Giovanni Marco
authors.initials: GM
authors.lastname: Dall'Olio
authors.affiliation: Institut de Biologia Evolutiva, CSIC-Universitat Pompeu Fabra, Barcelona, Catalonia, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Bertranpetit
authors.affiliation: Institute of Evolutionary Biology and Environmental Studies, University of Zurich, Zürich, Switzerland; The Swiss Institute of Bioinformatics, Lausanne, Switzerland; The Santa Fe Institute, Santa Fe, New Mexico, United States of America.
authors.forename: Andreas
authors.initials: A
authors.lastname: Wagner
authors.affiliation: Institut de Biologia Evolutiva, CSIC-Universitat Pompeu Fabra, Barcelona, Catalonia, Spain; Universitat Autonòma de Barcelona, Barcelona, Spain.
authors.forename: Hafid
authors.initials: H
authors.lastname: Laayouni
mesh_terms: D005075:Biological Evolution; D003198:Computer Simulation; D056726:Genetic Association Studies; D018740:Genetic Heterogeneity; D056426:Genetic Loci; D014644:Genetic Variation; D005828:Genetics, Population; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008957:Models, Genetic; D016366:Open Reading Frames; D049490:Systems Biology