title: Population genomics of intrapatient HIV-1 evolution.
abstract: Many microbial populations rapidly adapt to changing environments with multiple variants competing for survival. To quantify such complex evolutionary dynamics in vivo, time resolved and genome wide data including rare variants are essential. We performed whole-genome deep sequencing of HIV-1 populations in 9 untreated patients, with 6-12 longitudinal samples per patient spanning 5-8 years of infection. The data can be accessed and explored via an interactive web application. We show that patterns of minor diversity are reproducible between patients and mirror global HIV-1 diversity, suggesting a universal landscape of fitness costs that control diversity. Reversions towards the ancestral HIV-1 sequence are observed throughout infection and account for almost one third of all sequence changes. Reversion rates depend strongly on conservation. Frequent recombination limits linkage disequilibrium to about 100 bp in most of the genome, but strong hitch-hiking due to short range linkage limits diversity.
authors.affiliation: Evolutionary Dynamics and Biophysics, Max Planck Institute for Developmental Biology, Tübingen, Germany.
authors.forename: Fabio
authors.initials: F
authors.lastname: Zanini
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden.
authors.forename: Johanna
authors.initials: J
authors.lastname: Brodin
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden.
authors.forename: Lina
authors.initials: L
authors.lastname: Thebo
authors.affiliation: Evolutionary Dynamics and Biophysics, Max Planck Institute for Developmental Biology, Tübingen, Germany.
authors.forename: Christa
authors.initials: C
authors.lastname: Lanz
authors.affiliation: Department of Clinical Science and Education, Stockholm South General Hospital, Stockholm, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Bratt
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden.|Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Albert
authors.affiliation: Evolutionary Dynamics and Biophysics, Max Planck Institute for Developmental Biology, Tübingen, Germany.
authors.forename: Richard A
authors.identifier: http://orcid.org/0000-0003-2525-1407
authors.initials: RA
authors.lastname: Neher
mesh_terms: D008040:Genetic Linkage; D014644:Genetic Variation; D016679:Genome, Viral; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008137:Longitudinal Studies; D056186:Metagenomics; D009154:Mutation; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA
keywords: HIV-1; deep sequencing; evolution; evolutionary biology; fitness landscapes; genomics; infectious disease; microbiology; reversion; viruses