ArticleMolecular biology and evolution2022
Citrullination Was Introduced into Animals by Horizontal Gene Transfer from Cyanobacteria.
Article in Molecular biology and evolution, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 28 citations in OpenAlex.
- Detection and functional analysis of horizontal gene transfer events in the ciliateFrontiers in microbiology · 2026Article
- The citrullinating enzyme PADI4 governs progenitor cell proliferation and translation in developing hair follicles.Science advances · 2025Article
- Deep Learning Enhances Precision of Citrullination Identification in Human and Plant Tissue Proteomes.Molecular & cellular proteomics : MCP · 2025Article
- Fantastic proteins and where to find them - histones, in the nucleus and beyond.Journal of cell science · 2024Review
- Fantastic proteins and where to find them - histones, in the nucleus and beyond.Journal of cell science · 2024Review
- The fitness cost of spurious phosphorylation.The EMBO journal · 2024Article
- Horizontal gene transfer in eukaryotes: aligning theory with data.Nature reviews. Genetics · 2024Review
- Protein Citrullination by Peptidyl Arginine Deiminase/Arginine Deiminase Homologs in Members of the Human Microbiota and Its Recognition by Anti-Citrullinated Protein Antibodies.International journal of molecular sciences · 2024Article
- Evolutionary analysis reveals the role of a non-catalytic domain of peptidyl arginine deiminase 2 in transcriptional regulation.iScience · 2024Article
- Widespread horizontal gene transfer between plants and bacteria.ISME communications · 2024Article
- Extracellular vesicle signatures and protein citrullination are modified in shore crabs (Virulence · 2023Article
- Neutrophil attachment via Mac-1 (Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- Co-expression of PADI isoforms during progenitor differentiation enables functional diversity.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- The fitness cost of spurious phosphorylation.bioRxiv : the preprint server for biology · 2023Article
- Deciphering Evolutionary Trajectories of Lactate Dehydrogenases Provides New Insights into Allostery.Molecular biology and evolution · 2023Article
- Massive Somatic and Germline Chromosomal Integrations of Polydnaviruses in Lepidopterans.Molecular biology and evolution · 2023Article
- Peptidylarginine deiminase enzymes and citrullinated proteins in female reproductive physiology and associated diseases†.Biology of reproduction · 2022Review
- Multiple Horizontal Acquisitions of Plant Genes in the Whitefly Bemisia tabaci.Genome biology and evolution · 2022Article
- A Pilot Study on Peptidylarginine Deiminases and Protein Deimination in Animal Cancers across Vertebrate Species.International journal of molecular sciences · 2022Article
- The virtues and vices of protein citrullination.Royal Society open science · 2022Review
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Protein posttranslational modifications add great sophistication to biological systems. Citrullination, a key regulatory mechanism in human physiology and pathophysiology, is enigmatic from an evolutionary perspective. Although the citrullinating enzymes peptidylarginine deiminases (PADIs) are ubiquitous across vertebrates, they are absent from yeast, worms, and flies. Based on this distribution PADIs were proposed to have been horizontally transferred, but this has been contested. Here, we map the evolutionary trajectory of PADIs into the animal lineage. We present strong phylogenetic support for a clade encompassing animal and cyanobacterial PADIs that excludes fungal and other bacterial homologs. The animal and cyanobacterial PADI proteins share functionally relevant primary and tertiary synapomorphic sequences that are distinct from a second PADI type present in fungi and actinobacteria. Molecular clock calculations and sequence divergence analyses using the fossil record estimate the last common ancestor of the cyanobacterial and animal PADIs to be less than 1 billion years old. Additionally, under an assumption of vertical descent, PADI sequence change during this evolutionary time frame is anachronistically low, even when compared with products of likely endosymbiont gene transfer, mitochondrial proteins, and some of the most highly conserved sequences in life. The consilience of evidence indicates that PADIs were introduced from cyanobacteria into animals by horizontal gene transfer (HGT). The ancestral cyanobacterial PADI is enzymatically active and can citrullinate eukaryotic proteins, suggesting that the PADI HGT event introduced a new catalytic capability into the regulatory repertoire of animals. This study reveals the unusual evolution of a pleiotropic protein modification.
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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.