ArticlePLoS computational biology2016
Effects of Darwinian Selection and Mutability on Rate of Broadly Neutralizing Antibody Evolution during HIV-1 Infection.
Article in PLoS computational biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- TyCHE enables time-resolved lineage tracing of heterogeneously-evolving populations.bioRxiv : the preprint server for biology · 2025Article
- B cell phylogenetics in the single cell era.Trends in immunology · 2024Review
- Immunoglobulin VDJ repertoires reveal hallmarks of germinal centers in unique cell clusters isolated from zebrafish (Frontiers in immunology · 2022Article
- Article
- Genome edited B cells: a new frontier in immune cell therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- Coevolutionary transitions emerging from flexible molecular recognition and eco-evolutionary feedback.iScience · 2021Article
- Distinct clonal evolution of B-cells in HIV controllers with neutralizing antibody breadth.eLife · 2021Article
- Prospective Artificial Intelligence to Dissect the Dengue Immune Response and Discover Therapeutics.Frontiers in immunology · 2021Review
- Vaccine targeting SIVmac251 protease cleavage sites protects macaques against vaginal infection.The Journal of clinical investigation · 2020Article
- Article
- VRC34-Antibody Lineage Development Reveals How a Required Rare Mutation Shapes the Maturation of a Broad HIV-Neutralizing Lineage.Cell host & microbe · 2020Article
- Targeted selection of HIV-specific antibody mutations by engineering B cell maturation.Science (New York, N.Y.) · 2019Article
- Repertoire-wide phylogenetic models of B cell molecular evolution reveal evolutionary signatures of aging and vaccination.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Correction: Effects of Darwinian Selection and Mutability on Rate of Broadly Neutralizing Antibody Evolution during HIV-1 Infection.PLoS computational biology · 2019Article
- cAb-Rep: A Database of Curated Antibody Repertoires for Exploring Antibody Diversity and Predicting Antibody Prevalence.Frontiers in immunology · 2019Article
- The expanding array of HIV broadly neutralizing antibodies.Retrovirology · 2018Review
- Sequencing HIV-neutralizing antibody exons and introns reveals detailed aspects of lineage maturation.Nature communications · 2018Article
- Predicting B cell receptor substitution profiles using public repertoire data.PLoS computational biology · 2018Article
- Selection and Neutral Mutations Drive Pervasive Mutability Losses in Long-Lived Anti-HIV B-Cell Lineages.Molecular biology and evolution · 2018Article
- Computational Strategies for Dissecting the High-Dimensional Complexity of Adaptive Immune Repertoires.Frontiers in immunology · 2018Review
Corrections and comments
- Erratum issued
Authors and funding
7 authors.
Funding
Abstract
Accumulation of somatic mutations in antibody variable regions is critical for antibody affinity maturation, with HIV-1 broadly neutralizing antibodies (bnAbs) generally requiring years to develop. We recently found that the rate at which mutations accumulate decreases over time, but the mechanism governing this slowing is unclear. In this study, we investigated whether natural selection and/or mutability of the antibody variable region contributed significantly to observed decrease in rate. We used longitudinally sampled sequences of immunoglobulin transcripts of single lineages from each of 3 donors, as determined by next generation sequencing. We estimated the evolutionary rates of the complementarity determining regions (CDRs), which are most significant for functional selection, and found they evolved about 1.5- to 2- fold faster than the framework regions. We also analyzed the presence of AID hotspots and coldspots at different points in lineage development and observed an average decrease in mutability of less than 10 percent over time. Altogether, the correlation between Darwinian selection strength and evolutionary rate trended toward significance, especially for CDRs, but cannot fully explain the observed changes in evolutionary rate. The mutability modulated by AID hotspots and coldspots changes correlated only weakly with evolutionary rates. The combined effects of Darwinian selection and mutability contribute substantially to, but do not fully explain, evolutionary rate change for HIV-1-targeting bnAb lineages.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.