ArticlePLoS genetics2014
Selection on a variant associated with improved viral clearance drives local, adaptive pseudogenization of interferon lambda 4 (IFNL4).
Article in PLoS genetics, 2014. 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 60 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
60 citing papers in PubMed.
- IFNL4 genotype and other personal characteristics to predict response to 8-week sofosbuvir-based treatment for chronic hepatitis C.The Journal of infection · 2024Article
- Variants ofGenes · 2023Article
- Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2023Article
- Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2023Article
- Human and pathogen genotype-by-genotype interactions in the light of coevolution theory.PLoS genetics · 2023Review
- No Association of IFNL4 Genotype With Opportunistic Infections and Cancers Among Men With Human Immunodeficiency Virus 1 Infection.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023Article
- Maximum SNP FST Outperforms Full-Window Statistics for Detecting Soft Sweeps in Local Adaptation.Genome biology and evolution · 2022Article
- Historic and Prehistoric Epidemics: An Overview of Sources Available for the Study of Ancient Pathogens.Epidemiologia (Basel, Switzerland) · 2022Review
- IFNL4 rs368234815 polymorphism does not predict risk of BK virus associated nephropathy after living-donor kidney transplant: A case-control study.Clinical transplantation · 2022Article
- Article
- The role of IFNL4 in liver inflammation and progression of fibrosis.Genes and immunity · 2022Review
- Distinct molecular phenotypes involving several human diseases are induced by IFN-λ3 and IFN-λ4 in monocyte-derived macrophages.Genes and immunity · 2022Article
- Macrophages and neutrophils express IFNλs in granulomas fromFrontiers in immunology · 2022Article
- SARS-CoV-2 infection in India bucks the trend: Trained innate immunity?American journal of human biology : the official journal of the Human Biology Council · 2021Article
- Analysis of Genomic DNA from Medieval Plague Victims Suggests Long-Term Effect of Yersinia pestis on Human Immunity Genes.Molecular biology and evolution · 2021Article
- HepaticInternational journal of molecular sciences · 2021Article
- IFN-λ4 is associated with increased risk and earlier occurrence of several common infections in African children.Genes and immunity · 2021Article
- IFN-λ4 genetic variants influence clinical malaria episodes in a cohort of Kenyan children.Malaria journal · 2021Article
- Interferon-lambda 3 and 4 Polymorphisms Increase Sustained Virological Responses and Regulate Innate Immunity in Antiviral Therapy With Pegylated Interferon-Alpha.Frontiers in cellular and infection microbiology · 2021Article
- A Role of Variance in Interferon Genes to Disease Severity in COVID-19 Patients.Frontiers in genetics · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
8 authors.
Funding
Abstract
Interferon lambda 4 gene (IFNL4) encodes IFN-λ4, a new member of the IFN-λ family with antiviral activity. In humans IFNL4 open reading frame is truncated by a polymorphic frame-shift insertion that eliminates IFN-λ4 and turns IFNL4 into a polymorphic pseudogene. Functional IFN-λ4 has antiviral activity but the elimination of IFN-λ4 through pseudogenization is strongly associated with improved clearance of hepatitis C virus (HCV) infection. We show that functional IFN-λ4 is conserved and evolutionarily constrained in mammals and thus functionally relevant. However, the pseudogene has reached moderately high frequency in Africa, America, and Europe, and near fixation in East Asia. In fact, the pseudogenizing variant is among the 0.8% most differentiated SNPs between Africa and East Asia genome-wide. Its raise in frequency is associated with additional evidence of positive selection, which is strongest in East Asia, where this variant falls in the 0.5% tail of SNPs with strongest signatures of recent positive selection genome-wide. Using a new Approximate Bayesian Computation (ABC) approach we infer that the pseudogenizing allele appeared just before the out-of-Africa migration and was immediately targeted by moderate positive selection; selection subsequently strengthened in European and Asian populations resulting in the high frequency observed today. This provides evidence for a changing adaptive process that, by favoring IFN-λ4 inactivation, has shaped present-day phenotypic diversity and susceptibility to disease.
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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.