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Updated: Mar 5, 2026

An Integrated Approach for Microprotein Identification and Sequence Analysis
Published on: July 12, 2022
Cross-Species Genome-Wide Identification of Evolutionary Conserved MicroProteins
Daniel Straub1,2, Stephan Wenkel1,2
1Department of Plant and Environmental Sciences, University of Copenhagen, Frederiksberg C, Denmark.
Abstract:
MicroProteins are small single-domain proteins that act by engaging their targets into different, sometimes nonproductive protein complexes. In order to identify novel microProteins in any sequenced genome of interest, we have developed miPFinder, a program that identifies and classifies potential microProteins. In the past years, several microProteins have been discovered in plants where they are mainly involved in the regulation of development by fine-tuning transcription factor activities. The miPFinder algorithm identifies all up to date known plant microProteins and extends the microProtein concept beyond transcription factors to other protein families. Here, we reveal potential microProtein candidates in several plant and animal reference genomes. A large number of these microProteins are species-specific while others evolved early and are evolutionary highly conserved. Most known microProtein genes originated from large ancestral genes by gene duplication, mutation and subsequent degradation. Gene ontology analysis shows that putative microProtein ancestors are often located in the nucleus, and involved in DNA binding and formation of protein complexes. Additionally, microProtein candidates act in plant transcriptional regulation, signal transduction and anatomical structure development. MiPFinder is freely available to find microProteins in any genome and will aid in the identification of novel microProteins in plants and animals.
Insights
We developed miPFinder, a program to identify novel microProteins, small proteins regulating development. This tool analyzes genomes, revealing conserved and species-specific microProteins, aiding future research in plants and animals.
Area of Science:
- Genomics
- Proteomics
- Bioinformatics
Background:
- MicroProteins are small, single-domain proteins that regulate biological processes by forming protein complexes.
- Previously, microProteins were primarily identified in plants, where they fine-tune transcription factor activities for developmental regulation.
- The broader roles and evolutionary origins of microProteins across diverse species remained largely unexplored.
Purpose of the Study:
- To develop a computational tool, miPFinder, for identifying and classifying potential microProteins in any sequenced genome.
- To expand the known repertoire of microProteins beyond transcription factors and explore their presence in both plant and animal genomes.
- To investigate the evolutionary history and functional roles of identified microProtein candidates.
Main Methods:
- Development of the miPFinder algorithm for de novo identification and classification of microProteins.
- Application of miPFinder to multiple plant and animal reference genomes.
- Gene ontology analysis to infer the ancestral functions and cellular localization of microProtein precursors.
Main Results:
- miPFinder successfully identified known plant microProteins and discovered novel candidates in both plant and animal genomes.
- A significant number of identified microProteins were species-specific, while others showed early evolutionary origins and high conservation.
- Analysis revealed that microProtein genes often arise from large ancestral genes through duplication and degradation, with ancestors frequently involved in nuclear functions like DNA binding and complex formation.
- Putative microProteins are implicated in plant transcriptional regulation, signal transduction, and anatomical development.
Conclusions:
- miPFinder is an effective tool for discovering novel microProteins across diverse taxa.
- MicroProteins play diverse roles in biological regulation, extending beyond transcription factors.
- The evolutionary trajectory of microProteins involves gene duplication and degradation, highlighting their dynamic nature in genome evolution.
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