Evidence of natural selection in the mitochondrial-derived peptides humanin and SHLP6
Abstract Mitochondrial-derived peptides are encoded by mitochondrial DNA but have biological activity outside mitochondria. Eight of these are encoded by sequences within the mitochondrial 12S and 16S ribosomal genes: humanin, MOTS-c, and the six SHLP peptides, SHLP1-SHLP6. These peptides have vario...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-41053-0 |
| _version_ | 1797559521600602112 |
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| author | James M. Gruschus Daniel L. Morris Nico Tjandra |
| author_facet | James M. Gruschus Daniel L. Morris Nico Tjandra |
| author_sort | James M. Gruschus |
| collection | DOAJ |
| description | Abstract Mitochondrial-derived peptides are encoded by mitochondrial DNA but have biological activity outside mitochondria. Eight of these are encoded by sequences within the mitochondrial 12S and 16S ribosomal genes: humanin, MOTS-c, and the six SHLP peptides, SHLP1-SHLP6. These peptides have various effects in cell culture and animal models, affecting neuroprotection, insulin sensitivity, and apoptosis, and some are secreted, potentially having extracellular signaling roles. However, except for humanin, their importance in normal cell function is unknown. To gauge their importance, their coding sequences in vertebrates have been analyzed for synonymous codon bias. Because they lie in RNA genes, such bias should only occur if their amino acids have been conserved to maintain biological function. Humanin and SHLP6 show strong synonymous codon bias and sequence conservation. In contrast, SHLP1, SHLP2, SHLP3, and SHLP5 show no significant bias and are poorly conserved. MOTS-c and SHLP4 also lack significant bias, but contain highly conserved N-terminal regions, and their biological importance cannot be ruled out. An additional potential mitochondrial-derived peptide sequence was discovered preceding SHLP2, named SHLP2b, which also contains a highly conserved N-terminal region with synonymous codon bias. |
| first_indexed | 2024-03-10T17:46:35Z |
| format | Article |
| id | doaj.art-1b561065f4574dbf9e15c13b009c1777 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-10T17:46:35Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-1b561065f4574dbf9e15c13b009c17772023-11-20T09:28:55ZengNature PortfolioScientific Reports2045-23222023-08-0113111210.1038/s41598-023-41053-0Evidence of natural selection in the mitochondrial-derived peptides humanin and SHLP6James M. Gruschus0Daniel L. Morris1Nico Tjandra2Laboratory of Structural Biophysics, Biochemistry and Biophysics Center, NHLBI, NIHLaboratory of Structural Biophysics, Biochemistry and Biophysics Center, NHLBI, NIHLaboratory of Structural Biophysics, Biochemistry and Biophysics Center, NHLBI, NIHAbstract Mitochondrial-derived peptides are encoded by mitochondrial DNA but have biological activity outside mitochondria. Eight of these are encoded by sequences within the mitochondrial 12S and 16S ribosomal genes: humanin, MOTS-c, and the six SHLP peptides, SHLP1-SHLP6. These peptides have various effects in cell culture and animal models, affecting neuroprotection, insulin sensitivity, and apoptosis, and some are secreted, potentially having extracellular signaling roles. However, except for humanin, their importance in normal cell function is unknown. To gauge their importance, their coding sequences in vertebrates have been analyzed for synonymous codon bias. Because they lie in RNA genes, such bias should only occur if their amino acids have been conserved to maintain biological function. Humanin and SHLP6 show strong synonymous codon bias and sequence conservation. In contrast, SHLP1, SHLP2, SHLP3, and SHLP5 show no significant bias and are poorly conserved. MOTS-c and SHLP4 also lack significant bias, but contain highly conserved N-terminal regions, and their biological importance cannot be ruled out. An additional potential mitochondrial-derived peptide sequence was discovered preceding SHLP2, named SHLP2b, which also contains a highly conserved N-terminal region with synonymous codon bias.https://doi.org/10.1038/s41598-023-41053-0 |
| spellingShingle | James M. Gruschus Daniel L. Morris Nico Tjandra Evidence of natural selection in the mitochondrial-derived peptides humanin and SHLP6 Scientific Reports |
| title | Evidence of natural selection in the mitochondrial-derived peptides humanin and SHLP6 |
| title_full | Evidence of natural selection in the mitochondrial-derived peptides humanin and SHLP6 |
| title_fullStr | Evidence of natural selection in the mitochondrial-derived peptides humanin and SHLP6 |
| title_full_unstemmed | Evidence of natural selection in the mitochondrial-derived peptides humanin and SHLP6 |
| title_short | Evidence of natural selection in the mitochondrial-derived peptides humanin and SHLP6 |
| title_sort | evidence of natural selection in the mitochondrial derived peptides humanin and shlp6 |
| url | https://doi.org/10.1038/s41598-023-41053-0 |
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