Detecting genomic regions under selection is an important objective of population genetics. Typical analyses for this goal are based on exploiting genetic diversity patterns in present time data but rapid advances in DNA sequencing have increased the availability of time series genomic data. A common approach to analyze such data is to model the temporal evolution of an allele frequency as a Markov chain. Based on this principle, several methods have been proposed to infer selection intensity. One of their differences lies in how they model the transition probabilities of the Markov chain. Using the Wright-Fisher model is a natural choice but its computational cost is prohibitive for large population sizes so approximations to this model based on parametric distributions have been proposed. Here, we compared the performance of some of these approximations with respect to their power to detect selection and their estimation of the selection coefficient. We developped a new generic Hidden Markov Model likelihood calculator and applied it on genetic time series simulated under various evolutionary scenarios. The Beta with spikes approximation, which combines discrete fixation probabilities with a continuous Beta distribution, was found to perform consistently better than the others. This distribution provides an almost perfect fit to the Wright-Fisher model in terms of selection inference, for a computational cost that does not increase with population size. We further evaluated this model for population sizes not accessible to the Wright-Fisher model and illustrated its performance on a dataset of two divergently selected chicken populations.
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http://dx.doi.org/10.1534/g3.119.400778 | DOI Listing |
J Theor Biol
February 2025
Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, CH-1015, Switzerland; SIB Swiss Institute of Bioinformatics, Lausanne, CH-1015, Switzerland. Electronic address:
The Wright-Fisher model and the Moran model are both widely used in population genetics. They describe the time evolution of the frequency of an allele in a well-mixed population with fixed size. We propose a simple and tractable model which bridges the Wright-Fisher and the Moran descriptions.
View Article and Find Full Text PDFbioRxiv
November 2024
Department of Microbiology & Immunology, University of Michigan, Ann Arbor, MI, USA.
SARS-CoV-2 has undergone repeated and rapid evolution to circumvent host immunity. However, outside of prolonged infections in immunocompromised hosts, within-host positive selection has rarely been detected. The low diversity within-hosts and strong genetic linkage among genomic sites make accurately detecting positive selection difficult.
View Article and Find Full Text PDFJ Mol Evol
December 2024
Department of Genetics, Development and Cell Biology, Iowa State University, Ames, Iowa, IA, 50011, USA.
G3 (Bethesda)
January 2025
Department of Genomics and Evolutionary Biology, National Institute of Genetics, Mishima, Shizuoka, 411-8540, Japan.
Local adaptation is widely seen when species adapt to spatially heterogeneous environments. Although many theoretical studies have investigated the dynamics of local adaptation using 2-population models, there remains a need to extend the theoretical framework to continuous space settings, reflecting the real habitats of species. In this study, we use a multidimensional continuous space model and mathematically analyze the establishment process of local adaptation, with a specific emphasis on the relative roles of mutation and migration.
View Article and Find Full Text PDFJ Math Biol
November 2024
University of Torino and Collegio Carlo Alberto, Turin, Italy.
Coupled Wright-Fisher diffusions have been recently introduced to model the temporal evolution of finitely-many allele frequencies at several loci. These are vectors of multidimensional diffusions whose dynamics are weakly coupled among loci through interaction coefficients, which make the reproductive rates for each allele depend on its frequencies at several loci. Here we consider the problem of filtering a coupled Wright-Fisher diffusion with parent-independent mutation, when this is seen as an unobserved signal in a hidden Markov model.
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