Investigation of the Molecular Evolution of Treg Suppression Mechanisms Indicates a Convergent Origin
Regulatory T cell (Treg) suppression of conventional T cells is a central mechanism that ensures immune system homeostasis. The exact time point of Treg emergence is still disputed. Furthermore, the time of Treg-mediated suppression mechanisms’ emergence has not been identified. It is not yet known...
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MDPI AG
2023-01-01
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| Series: | Current Issues in Molecular Biology |
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| Online Access: | https://www.mdpi.com/1467-3045/45/1/42 |
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| author | Suniti Bhaumik Marzena Łazarczyk Norwin Kubick Pavel Klimovich Agata Gurba Justyna Paszkiewicz Patrycja Teodorowicz Tomasz Kocki Jarosław Olav Horbańczuk Gina Manda Mariusz Sacharczuk Michel-Edwar Mickael |
| author_facet | Suniti Bhaumik Marzena Łazarczyk Norwin Kubick Pavel Klimovich Agata Gurba Justyna Paszkiewicz Patrycja Teodorowicz Tomasz Kocki Jarosław Olav Horbańczuk Gina Manda Mariusz Sacharczuk Michel-Edwar Mickael |
| author_sort | Suniti Bhaumik |
| collection | DOAJ |
| description | Regulatory T cell (Treg) suppression of conventional T cells is a central mechanism that ensures immune system homeostasis. The exact time point of Treg emergence is still disputed. Furthermore, the time of Treg-mediated suppression mechanisms’ emergence has not been identified. It is not yet known whether Treg suppression mechanisms diverged from a single pathway or converged from several sources. We investigated the evolutionary history of Treg suppression pathways using various phylogenetic analysis tools. To ensure the conservation of function for investigated proteins, we augmented our study using nonhomology-based methods to predict protein functions among various investigated species and mined the literature for experimental evidence of functional convergence. Our results indicate that a minority of Treg suppressor mechanisms could be homologs of ancient conserved pathways. For example, CD73, an enzymatic pathway known to play an essential role in invertebrates, is highly conserved between invertebrates and vertebrates, with no evidence of positive selection (w = 0.48, <i>p</i>-value < 0.00001). Our findings indicate that Tregs utilize homologs of proteins that diverged in early vertebrates. However, our findings do not exclude the possibility of a more evolutionary pattern following the duplication degeneration–complementation (DDC) model. Ancestral sequence reconstruction showed that Treg suppression mechanism proteins do not belong to one family; rather, their emergence seems to follow a convergent evolutionary pattern. |
| first_indexed | 2024-03-09T13:08:04Z |
| format | Article |
| id | doaj.art-d498a33de9cb4813a1f4af7d87ed0cd0 |
| institution | Directory Open Access Journal |
| issn | 1467-3037 1467-3045 |
| language | English |
| last_indexed | 2024-03-09T13:08:04Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Issues in Molecular Biology |
| spelling | doaj.art-d498a33de9cb4813a1f4af7d87ed0cd02023-11-30T21:45:34ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452023-01-0145162864810.3390/cimb45010042Investigation of the Molecular Evolution of Treg Suppression Mechanisms Indicates a Convergent OriginSuniti Bhaumik0Marzena Łazarczyk1Norwin Kubick2Pavel Klimovich3Agata Gurba4Justyna Paszkiewicz5Patrycja Teodorowicz6Tomasz Kocki7Jarosław Olav Horbańczuk8Gina Manda9Mariusz Sacharczuk10Michel-Edwar Mickael11Department of Pathology, University of Alabama at Birmingham, 845-19th St. South, Birmingham, AL 35294-2170, USADepartment of Experimental Genomics, Institute of Animal Biotechnology and Genetics, Polish Academy of Science, Postępu 36A, 05-552 Jastrzebiec, PolandDepartment of Biology, Institute of Plant Science and Microbiology, Univeristy of Hamburg, Ohnhorststr. 18, 22609 Hamburg, GermanyDepartment of Immunology, PM Forskningscentreum, 17854 Ekerö, SwedenDepartment of Pharmacodynamics, Faculty of Pharmacy, Warsaw Medical University, l Banacha 1, 02-697 Warsaw, PolandDepartment of Health, John Paul II University of Applied Sciences in Biala Podlaska, Sidorska 95/97, 21-500 Biała Podlaska, PolandDepartment of Health, John Paul II University of Applied Sciences in Biala Podlaska, Sidorska 95/97, 21-500 Biała Podlaska, PolandDepartment of Experimental and Clinical Pharmacology, Medical University of Lublin, Jaczewskiego 8b, 20-090 Lublin, PolandInstitute of Genetics and Animal Breeding, Polish Academy of Sciences, 05-552 Jastrzębiec, PolandRadiobiology Laboratory, Victor Babes National Institute of Pathology, 99-101 Splaiul Independentei, 050096 Bucharest, RomaniaDepartment of Experimental Genomics, Institute of Animal Biotechnology and Genetics, Polish Academy of Science, Postępu 36A, 05-552 Jastrzebiec, PolandDepartment of Experimental Genomics, Institute of Animal Biotechnology and Genetics, Polish Academy of Science, Postępu 36A, 05-552 Jastrzebiec, PolandRegulatory T cell (Treg) suppression of conventional T cells is a central mechanism that ensures immune system homeostasis. The exact time point of Treg emergence is still disputed. Furthermore, the time of Treg-mediated suppression mechanisms’ emergence has not been identified. It is not yet known whether Treg suppression mechanisms diverged from a single pathway or converged from several sources. We investigated the evolutionary history of Treg suppression pathways using various phylogenetic analysis tools. To ensure the conservation of function for investigated proteins, we augmented our study using nonhomology-based methods to predict protein functions among various investigated species and mined the literature for experimental evidence of functional convergence. Our results indicate that a minority of Treg suppressor mechanisms could be homologs of ancient conserved pathways. For example, CD73, an enzymatic pathway known to play an essential role in invertebrates, is highly conserved between invertebrates and vertebrates, with no evidence of positive selection (w = 0.48, <i>p</i>-value < 0.00001). Our findings indicate that Tregs utilize homologs of proteins that diverged in early vertebrates. However, our findings do not exclude the possibility of a more evolutionary pattern following the duplication degeneration–complementation (DDC) model. Ancestral sequence reconstruction showed that Treg suppression mechanism proteins do not belong to one family; rather, their emergence seems to follow a convergent evolutionary pattern.https://www.mdpi.com/1467-3045/45/1/42Tregsevolutionai |
| spellingShingle | Suniti Bhaumik Marzena Łazarczyk Norwin Kubick Pavel Klimovich Agata Gurba Justyna Paszkiewicz Patrycja Teodorowicz Tomasz Kocki Jarosław Olav Horbańczuk Gina Manda Mariusz Sacharczuk Michel-Edwar Mickael Investigation of the Molecular Evolution of Treg Suppression Mechanisms Indicates a Convergent Origin Current Issues in Molecular Biology Tregs evolution ai |
| title | Investigation of the Molecular Evolution of Treg Suppression Mechanisms Indicates a Convergent Origin |
| title_full | Investigation of the Molecular Evolution of Treg Suppression Mechanisms Indicates a Convergent Origin |
| title_fullStr | Investigation of the Molecular Evolution of Treg Suppression Mechanisms Indicates a Convergent Origin |
| title_full_unstemmed | Investigation of the Molecular Evolution of Treg Suppression Mechanisms Indicates a Convergent Origin |
| title_short | Investigation of the Molecular Evolution of Treg Suppression Mechanisms Indicates a Convergent Origin |
| title_sort | investigation of the molecular evolution of treg suppression mechanisms indicates a convergent origin |
| topic | Tregs evolution ai |
| url | https://www.mdpi.com/1467-3045/45/1/42 |
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