Discovery of Evolutionary Loss of the Ubiquitin-like Autophagy-Related ATG12 System in a Lineage of Apicomplexa
The autophagy-related ubiquitin-like conjugation systems, the ATG8 and ATG12 systems, are universally conserved in eukaryotes. However, the covalent bond in the ATG12 system has recently been shown to be evolutionarily lost in Apicomplexa. Here, we show that all genes associated with the ATG12 syste...
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2025-01-01
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| author | Xiaoxia X. Lin Yun D. Bai Sichang T. Wang Akira Nozawa Tatsuya Sawasaki Tatsunori Masatani Kenji Hikosaka Masahito Asada Hirokazu Sakamoto |
| author_facet | Xiaoxia X. Lin Yun D. Bai Sichang T. Wang Akira Nozawa Tatsuya Sawasaki Tatsunori Masatani Kenji Hikosaka Masahito Asada Hirokazu Sakamoto |
| author_sort | Xiaoxia X. Lin |
| collection | DOAJ |
| description | The autophagy-related ubiquitin-like conjugation systems, the ATG8 and ATG12 systems, are universally conserved in eukaryotes. However, the covalent bond in the ATG12 system has recently been shown to be evolutionarily lost in Apicomplexa. Here, we show that all genes associated with the ATG12 system are absent in piroplasmida, a lineage within Apicomplexa. Comparative genomics of ATGs further shows that piroplasm ATG3 has lost the region necessary for ATG12 binding. However, our in vitro functional analysis using recombinant proteins demonstrated that ATG3 retained the ability to interact with ATG8 in <i>Babesia bovis</i>, a model species in piroplasmida. These findings provide evidence that the ATG8 system is functional, while the ATG12 system is completely lost in the common ancestor of piroplasmida and highlight the evolutionary flexibility of the ATG12 system in Apicomplexa. |
| format | Article |
| id | doaj-art-3b4e0e4759c84d9cba36185cd62ac612 |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| series | Cells |
| spelling | doaj-art-3b4e0e4759c84d9cba36185cd62ac6122025-01-24T13:26:45ZengMDPI AGCells2073-44092025-01-0114212110.3390/cells14020121Discovery of Evolutionary Loss of the Ubiquitin-like Autophagy-Related ATG12 System in a Lineage of ApicomplexaXiaoxia X. Lin0Yun D. Bai1Sichang T. Wang2Akira Nozawa3Tatsuya Sawasaki4Tatsunori Masatani5Kenji Hikosaka6Masahito Asada7Hirokazu Sakamoto8Department of Infection and Host Defense, Graduate School of Medicine, Chiba University, Chiba 263-8522, JapanDepartment of Infection and Host Defense, Graduate School of Medicine, Chiba University, Chiba 263-8522, JapanDepartment of Infection and Host Defense, Graduate School of Medicine, Chiba University, Chiba 263-8522, JapanProteo-Science Center (PROS), Ehime University, Matsuyama 790-0825, JapanProteo-Science Center (PROS), Ehime University, Matsuyama 790-0825, JapanLaboratory of Zoonotic Diseases, Faculty of Applied Biological Sciences, Gifu University, Gifu 501-1193, JapanDepartment of Infection and Host Defense, Graduate School of Medicine, Chiba University, Chiba 263-8522, JapanNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Hokkaido 080-0834, JapanDepartment of Infection and Host Defense, Graduate School of Medicine, Chiba University, Chiba 263-8522, JapanThe autophagy-related ubiquitin-like conjugation systems, the ATG8 and ATG12 systems, are universally conserved in eukaryotes. However, the covalent bond in the ATG12 system has recently been shown to be evolutionarily lost in Apicomplexa. Here, we show that all genes associated with the ATG12 system are absent in piroplasmida, a lineage within Apicomplexa. Comparative genomics of ATGs further shows that piroplasm ATG3 has lost the region necessary for ATG12 binding. However, our in vitro functional analysis using recombinant proteins demonstrated that ATG3 retained the ability to interact with ATG8 in <i>Babesia bovis</i>, a model species in piroplasmida. These findings provide evidence that the ATG8 system is functional, while the ATG12 system is completely lost in the common ancestor of piroplasmida and highlight the evolutionary flexibility of the ATG12 system in Apicomplexa.https://www.mdpi.com/2073-4409/14/2/121autophagyATG12 systemApicomplexapiroplasmida |
| spellingShingle | Xiaoxia X. Lin Yun D. Bai Sichang T. Wang Akira Nozawa Tatsuya Sawasaki Tatsunori Masatani Kenji Hikosaka Masahito Asada Hirokazu Sakamoto Discovery of Evolutionary Loss of the Ubiquitin-like Autophagy-Related ATG12 System in a Lineage of Apicomplexa Cells autophagy ATG12 system Apicomplexa piroplasmida |
| title | Discovery of Evolutionary Loss of the Ubiquitin-like Autophagy-Related ATG12 System in a Lineage of Apicomplexa |
| title_full | Discovery of Evolutionary Loss of the Ubiquitin-like Autophagy-Related ATG12 System in a Lineage of Apicomplexa |
| title_fullStr | Discovery of Evolutionary Loss of the Ubiquitin-like Autophagy-Related ATG12 System in a Lineage of Apicomplexa |
| title_full_unstemmed | Discovery of Evolutionary Loss of the Ubiquitin-like Autophagy-Related ATG12 System in a Lineage of Apicomplexa |
| title_short | Discovery of Evolutionary Loss of the Ubiquitin-like Autophagy-Related ATG12 System in a Lineage of Apicomplexa |
| title_sort | discovery of evolutionary loss of the ubiquitin like autophagy related atg12 system in a lineage of apicomplexa |
| topic | autophagy ATG12 system Apicomplexa piroplasmida |
| url | https://www.mdpi.com/2073-4409/14/2/121 |
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