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Article

Evolutionary Characterization of the Short Protein SPAAR

1
Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
2
Pittsburgh Center for Evolutionary Biology and Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
3
Joint CMU-Pitt Ph.D. Program in Computational Biology, University of Pittsburgh, Pittsburgh, PA 15213, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Manyuan Long and Esther Betran
Genes 2021, 12(12), 1864; https://doi.org/10.3390/genes12121864
Received: 23 October 2021 / Revised: 22 November 2021 / Accepted: 22 November 2021 / Published: 24 November 2021
(This article belongs to the Special Issue How Do New Genes Originate and Evolve?)
Microproteins (<100 amino acids) are receiving increasing recognition as important participants in numerous biological processes, but their evolutionary dynamics are poorly understood. SPAAR is a recently discovered microprotein that regulates muscle regeneration and angiogenesis through interactions with conserved signaling pathways. Interestingly, SPAAR does not belong to any known protein family and has known homologs exclusively among placental mammals. This lack of distant homology could be caused by challenges in homology detection of short sequences, or it could indicate a recent de novo emergence from a noncoding sequence. By integrating syntenic alignments and homology searches, we identify SPAAR orthologs in marsupials and monotremes, establishing that SPAAR has existed at least since the emergence of mammals. SPAAR shows substantial primary sequence divergence but retains a conserved protein structure. In primates, we infer two independent evolutionary events leading to the de novo origination of 5′ elongated isoforms of SPAAR from a noncoding sequence and find evidence of adaptive evolution in this extended region. Thus, SPAAR may be of ancient origin, but it appears to be experiencing continual evolutionary innovation in mammals. View Full-Text
Keywords: microproteins; gene annotation; homology detection; de novo gene birth; protein evolution; adaptation; lncRNAs; noncanonical translation; comparative genomics; mTOR pathway microproteins; gene annotation; homology detection; de novo gene birth; protein evolution; adaptation; lncRNAs; noncanonical translation; comparative genomics; mTOR pathway
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MDPI and ACS Style

Lee, J.; Wacholder, A.; Carvunis, A.-R. Evolutionary Characterization of the Short Protein SPAAR. Genes 2021, 12, 1864. https://doi.org/10.3390/genes12121864

AMA Style

Lee J, Wacholder A, Carvunis A-R. Evolutionary Characterization of the Short Protein SPAAR. Genes. 2021; 12(12):1864. https://doi.org/10.3390/genes12121864

Chicago/Turabian Style

Lee, Jiwon, Aaron Wacholder, and Anne-Ruxandra Carvunis. 2021. "Evolutionary Characterization of the Short Protein SPAAR" Genes 12, no. 12: 1864. https://doi.org/10.3390/genes12121864

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