Title: Clonal interference can cause wavelet-like oscillations of multilocus linkage disequilibrium
Authors : Garcia, Victor
Glassberg, Emily C.
Harpak, Arbel
Feldman, Marcus W.
Published in : Journal of The Royal Society Interface
Volume(Issue) : 15
Issue : 140
Publisher / Ed. Institution : The Royal Society
Issue Date: 21-Mar-2018
License (according to publishing contract) : Licence according to publishing contract
Type of review: Peer review (Publication)
Language : English
Subjects : Genetic interference; Human immunodeficiency virus; Multilocus linkage disequilibrium
Subject (DDC) : 572: Biochemistry
616: Internal medicine and diseases
Abstract: Within-host adaptation of pathogens such as human immunodeficiency virus (HIV) often occurs at more than two loci. Multiple beneficial mutations may arise simultaneously on different genetic backgrounds and interfere, affecting each other's fixation trajectories. Here, we explore how these evolutionary dynamics are mirrored in multilocus linkage disequilibrium (MLD), a measure of multi-way associations between alleles. In the parameter regime corresponding to HIV, we show that deterministic early infection models induce MLD to oscillate over time in a wavelet-like fashion. We find that the frequency of these oscillations is proportional to the rate of adaptation. This signature is robust to drift, but can be eroded by high variation in fitness effects of beneficial mutations. Our findings suggest that MLD oscillations could be used as a signature of interference among multiple equally advantageous mutations and may aid the interpretation of MLD in data.
Departement: Life Sciences und Facility Management
Organisational Unit: Institute of Applied Simulation (IAS)
Publication type: Article in scientific Journal
DOI : 10.1098/rsif.2017.0921
ISSN: 1742-5689
1742-5662
URI: https://digitalcollection.zhaw.ch/handle/11475/7498
Appears in Collections:Publikationen Life Sciences und Facility Management

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