ArticleBMC ecology and evolution2021
Positive natural selection in primate genes of the type I interferon response.
Article in BMC ecology and evolution, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- A chicken interferon stimulated gene screen reveals limited genes restricting influenza replication.bioRxiv : the preprint server for biology · 2026Article
- Evolutionary Complexity of Primate Immune System Uncovered by the Extensive Phylogenomic Sampling.Genome biology and evolution · 2026Article
- Mammalian antiviral proteins ZAP and KHNYN can independently restrict CpG-enriched avian viruses.PLoS biology · 2025Article
- Mammalian ZAP and KHNYN can independently restrict CpG-enriched avian viruses.bioRxiv : the preprint server for biology · 2025Article
- Genetic Architecture of Immune Cell DNA Methylation in the Rhesus Macaque.Molecular ecology · 2025Article
- A Structure-Based Computational Pipeline for Broad-Spectrum Antiviral Discovery.bioRxiv : the preprint server for biology · 2025Article
- Evolutionary divergence of induced versus constitutive antiviral gene expression levels between primates and rodents.PLoS computational biology · 2025Article
- Adaptation of CD4 in gorillas and chimpanzees conveyed resistance to simian immunodeficiency viruses.eLife · 2025Article
- Systems immunology of transcriptional responses to viral infection identifies conserved antiviral pathways across macaques and humans.Cell reports · 2024Article
- Nascent transcription upon interferon-α2 stimulation on human and rhesus macaque lymphoblastoid cell lines.BMC research notes · 2023Article
- A Nuclear Export Signal in KHNYN Required for Its Antiviral Activity Evolved as ZAP Emerged in Tetrapods.Journal of virology · 2023Article
- Running With Scissors: Evolutionary Conflicts Between Viral Proteases and the Host Immune System.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundThe Type I interferon response is an important first-line defense against viruses. In turn, viruses antagonize (i.e., degrade, mis-localize, etc.) many proteins in interferon pathways. Thus, hosts and viruses are locked in an evolutionary arms race for dominance of the Type I interferon pathway. As a result, many genes in interferon pathways have experienced positive natural selection in favor of new allelic forms that can better recognize viruses or escape viral antagonists. Here, we performed a holistic analysis of selective pressures acting on genes in the Type I interferon family. We initially hypothesized that the genes responsible for inducing the production of interferon would be antagonized more heavily by viruses than genes that are turned on as a result of interferon. Our logic was that viruses would have greater effect if they worked upstream of the production of interferon molecules because, once interferon is produced, hundreds of interferon-stimulated proteins would activate and the virus would need to counteract them one-by-one.
resultsWe curated multiple sequence alignments of primate orthologs for 131 genes active in interferon production and signaling (herein, "induction" genes), 100 interferon-stimulated genes, and 100 randomly chosen genes. We analyzed each multiple sequence alignment for the signatures of recurrent positive selection. Counter to our hypothesis, we found the interferon-stimulated genes, and not interferon induction genes, are evolving significantly more rapidly than a random set of genes. Interferon induction genes evolve in a way that is indistinguishable from a matched set of random genes (22% and 18% of genes bear signatures of positive selection, respectively). In contrast, interferon-stimulated genes evolve differently, with 33% of genes evolving under positive selection and containing a significantly higher fraction of codons that have experienced selection for recurrent replacement of the encoded amino acid.
conclusionViruses may antagonize individual products of the interferon response more often than trying to neutralize the system altogether.
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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.