Evolutionary Characterization of the Short Protein SPAAR
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 interact...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/12/12/1864 |
| _version_ | 1797504321904967680 |
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| author | Jiwon Lee Aaron Wacholder Anne-Ruxandra Carvunis |
| author_facet | Jiwon Lee Aaron Wacholder Anne-Ruxandra Carvunis |
| author_sort | Jiwon Lee |
| collection | DOAJ |
| description | 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 <i>de novo</i> 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 <i>de novo</i> 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. |
| first_indexed | 2024-03-10T04:02:58Z |
| format | Article |
| id | doaj.art-089c11fa91b74acca45a7b0fe3744d89 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T04:02:58Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-089c11fa91b74acca45a7b0fe3744d892023-11-23T08:29:34ZengMDPI AGGenes2073-44252021-11-011212186410.3390/genes12121864Evolutionary Characterization of the Short Protein SPAARJiwon Lee0Aaron Wacholder1Anne-Ruxandra Carvunis2Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USAMicroproteins (<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 <i>de novo</i> 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 <i>de novo</i> 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.https://www.mdpi.com/2073-4425/12/12/1864microproteinsgene annotationhomology detection<i>de novo</i> gene birthprotein evolutionadaptation |
| spellingShingle | Jiwon Lee Aaron Wacholder Anne-Ruxandra Carvunis Evolutionary Characterization of the Short Protein SPAAR Genes microproteins gene annotation homology detection <i>de novo</i> gene birth protein evolution adaptation |
| title | Evolutionary Characterization of the Short Protein SPAAR |
| title_full | Evolutionary Characterization of the Short Protein SPAAR |
| title_fullStr | Evolutionary Characterization of the Short Protein SPAAR |
| title_full_unstemmed | Evolutionary Characterization of the Short Protein SPAAR |
| title_short | Evolutionary Characterization of the Short Protein SPAAR |
| title_sort | evolutionary characterization of the short protein spaar |
| topic | microproteins gene annotation homology detection <i>de novo</i> gene birth protein evolution adaptation |
| url | https://www.mdpi.com/2073-4425/12/12/1864 |
| work_keys_str_mv | AT jiwonlee evolutionarycharacterizationoftheshortproteinspaar AT aaronwacholder evolutionarycharacterizationoftheshortproteinspaar AT anneruxandracarvunis evolutionarycharacterizationoftheshortproteinspaar |