The role of gene duplication and paralog specialisation in the evolution of the mammalian PRPS complex
Abstract The phosphoribosyl pyrophosphate synthetase (PRPS) enzyme catalyzes a chokepoint reaction in nucleotide production, making it essential for life. Here, we show that the presence of multiple PRPS-encoding genes is a hallmark trait of eukaryotes, and we find that gains or losses of paralogs a...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61216-z |
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| author | Bibek R. Karki Austin C. MacMillan Sara Vicente-Muñoz Kenneth D. Greis Lindsey E. Romick John T. Cunningham |
| author_facet | Bibek R. Karki Austin C. MacMillan Sara Vicente-Muñoz Kenneth D. Greis Lindsey E. Romick John T. Cunningham |
| author_sort | Bibek R. Karki |
| collection | DOAJ |
| description | Abstract The phosphoribosyl pyrophosphate synthetase (PRPS) enzyme catalyzes a chokepoint reaction in nucleotide production, making it essential for life. Here, we show that the presence of multiple PRPS-encoding genes is a hallmark trait of eukaryotes, and we find that gains or losses of paralogs are associated with major branching events in the eukaryotic tree. We pinpoint the evolutionary origins and define the individual roles for each of the mammalian PRPS paralogs, which we demonstrate work together as a heterogeneous multicomponent complex. Employing isogenic cells representing all viable individual or combinatorial assembly states, we dissect the basic organizational principles of the enzyme complex and characterize the emergent properties responsible for paralog specialization, including new modes of regulation that govern complex assembly and activity in vivo. Collectively, our study demonstrates how evolution has transformed a single PRPS enzyme into a biochemical complex endowed with novel functional and regulatory features that fine-tune mammalian metabolism. |
| format | Article |
| id | doaj-art-82b537290dea4adaa0dd376b2e4e17ed |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-82b537290dea4adaa0dd376b2e4e17ed2025-08-20T03:43:16ZengNature PortfolioNature Communications2041-17232025-07-0116111810.1038/s41467-025-61216-zThe role of gene duplication and paralog specialisation in the evolution of the mammalian PRPS complexBibek R. Karki0Austin C. MacMillan1Sara Vicente-Muñoz2Kenneth D. Greis3Lindsey E. Romick4John T. Cunningham5Department of Cancer Biology, University of Cincinnati College of MedicineDepartment of Cancer Biology, University of Cincinnati College of MedicineDivision of Pathology and Laboratory Medicine, Cincinnati Children’s Hospital Medical CenterDepartment of Cancer Biology, University of Cincinnati College of MedicineDivision of Pathology and Laboratory Medicine, Cincinnati Children’s Hospital Medical CenterDepartment of Cancer Biology, University of Cincinnati College of MedicineAbstract The phosphoribosyl pyrophosphate synthetase (PRPS) enzyme catalyzes a chokepoint reaction in nucleotide production, making it essential for life. Here, we show that the presence of multiple PRPS-encoding genes is a hallmark trait of eukaryotes, and we find that gains or losses of paralogs are associated with major branching events in the eukaryotic tree. We pinpoint the evolutionary origins and define the individual roles for each of the mammalian PRPS paralogs, which we demonstrate work together as a heterogeneous multicomponent complex. Employing isogenic cells representing all viable individual or combinatorial assembly states, we dissect the basic organizational principles of the enzyme complex and characterize the emergent properties responsible for paralog specialization, including new modes of regulation that govern complex assembly and activity in vivo. Collectively, our study demonstrates how evolution has transformed a single PRPS enzyme into a biochemical complex endowed with novel functional and regulatory features that fine-tune mammalian metabolism.https://doi.org/10.1038/s41467-025-61216-z |
| spellingShingle | Bibek R. Karki Austin C. MacMillan Sara Vicente-Muñoz Kenneth D. Greis Lindsey E. Romick John T. Cunningham The role of gene duplication and paralog specialisation in the evolution of the mammalian PRPS complex Nature Communications |
| title | The role of gene duplication and paralog specialisation in the evolution of the mammalian PRPS complex |
| title_full | The role of gene duplication and paralog specialisation in the evolution of the mammalian PRPS complex |
| title_fullStr | The role of gene duplication and paralog specialisation in the evolution of the mammalian PRPS complex |
| title_full_unstemmed | The role of gene duplication and paralog specialisation in the evolution of the mammalian PRPS complex |
| title_short | The role of gene duplication and paralog specialisation in the evolution of the mammalian PRPS complex |
| title_sort | role of gene duplication and paralog specialisation in the evolution of the mammalian prps complex |
| url | https://doi.org/10.1038/s41467-025-61216-z |
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