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Strand-Specific Analysis of Proteins at Replicating DNA Strands by Enrichment and Sequencing of Protein-Associated Nascent DNA Method
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Evolutionary Characterization of the Short Protein SPAAR
Jiwon Lee1,2,3, Aaron Wacholder1,2, Anne-Ruxandra Carvunis1,2
1Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Genes
|December 24, 2021
Summary
The microprotein SPAAR, crucial for muscle regeneration, has ancient mammalian origins but shows ongoing evolution. New isoforms have emerged de novo, indicating continuous innovation in mammals.
Area of Science:
- Evolutionary biology
- Molecular biology
- Genomics
Background:
- Microproteins are increasingly recognized for diverse biological roles.
- The evolutionary history of microproteins, like SPAAR, is largely unknown.
- SPAAR regulates muscle regeneration and angiogenesis but lacks distant homologs.
Purpose of the Study:
- To investigate the evolutionary origins and dynamics of the microprotein SPAAR.
- To determine if SPAAR is ancient or a recent de novo invention.
- To explore evolutionary innovations in SPAAR across mammalian lineages.
Main Methods:
- Comparative genomics integrating syntenic alignments.
- Homology searches across diverse mammalian species.
- Analysis of protein sequence and structural conservation.
Main Results:
- SPAAR orthologs were identified in marsupials and monotremes, indicating ancient mammalian origin.
- SPAAR exhibits significant sequence divergence but conserved protein structure.
- Two independent de novo origins of 5' elongated SPAAR isoforms were detected in primates.
- Evidence of adaptive evolution in the extended 5' region of primate SPAAR isoforms.
Conclusions:
- SPAAR is an ancient microprotein with a conserved structure dating back to the common ancestor of mammals.
- SPAAR is subject to ongoing evolutionary innovation, particularly in primates.
- De novo origination from noncoding DNA is a mechanism for generating novel microproteins.
Keywords:
adaptationcomparative genomicsde novo gene birthgene annotationhomology detectionlncRNAsmTOR pathwaymicroproteinsnoncanonical translationprotein evolutionMore Related Videos
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