Evolutionary Origin of <i>MUTYH</i> Germline Pathogenic Variations in Modern Humans
MUTYH plays an essential role in preventing oxidation-caused DNA damage. Pathogenic germline variations in <i>MUTYH</i> damage its function, causing intestinal polyposis and colorectal cancer. Determination of the evolutionary origin of the variation is essential to understanding the eti...
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| Format: | Article |
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MDPI AG
2023-02-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/3/429 |
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| author | Fengxia Xiao Jiaheng Li Philip Naderev Panuringan Lagniton Si Hoi Kou Huijun Lei Benjamin Tam San Ming Wang |
| author_facet | Fengxia Xiao Jiaheng Li Philip Naderev Panuringan Lagniton Si Hoi Kou Huijun Lei Benjamin Tam San Ming Wang |
| author_sort | Fengxia Xiao |
| collection | DOAJ |
| description | MUTYH plays an essential role in preventing oxidation-caused DNA damage. Pathogenic germline variations in <i>MUTYH</i> damage its function, causing intestinal polyposis and colorectal cancer. Determination of the evolutionary origin of the variation is essential to understanding the etiological relationship between <i>MUTYH</i> variation and cancer development. In this study, we analyzed the origins of pathogenic germline variants in human <i>MUTYH</i>. Using a phylogenic approach, we searched <i>MUTYH</i> pathogenic variants in modern humans in the <i>MUTYH</i> of 99 vertebrates across eight clades. We did not find pathogenic variants shared between modern humans and the non-human vertebrates following the evolutionary tree, ruling out the possibility of cross-species conservation as the origin of human pathogenic variants in <i>MUTYH</i>. We then searched the variants in the <i>MUTYH</i> of 5031 ancient humans and extinct Neanderthals and Denisovans. We identified 24 pathogenic variants in 42 ancient humans dated between 30,570 and 480 years before present (BP), and three pathogenic variants in Neanderthals dated between 65,000 and 38,310 years BP. Data from our study revealed that human <i>MUTYH</i> pathogenic variants mostly arose in recent human history and partially originated from Neanderthals. |
| first_indexed | 2024-03-11T06:52:16Z |
| format | Article |
| id | doaj.art-262f74baf7e34e8ea72fff1050f9009f |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-11T06:52:16Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-262f74baf7e34e8ea72fff1050f9009f2023-11-17T09:51:08ZengMDPI AGBiomolecules2218-273X2023-02-0113342910.3390/biom13030429Evolutionary Origin of <i>MUTYH</i> Germline Pathogenic Variations in Modern HumansFengxia Xiao0Jiaheng Li1Philip Naderev Panuringan Lagniton2Si Hoi Kou3Huijun Lei4Benjamin Tam5San Ming Wang6Ministry of Education Frontiers Science Center for Precision Oncology, Cancer Centre and Institute of Translational Medicine, Department of Public Health and Medical Administration, Faculty of Health Sciences, University of Macau, Macao, ChinaMinistry of Education Frontiers Science Center for Precision Oncology, Cancer Centre and Institute of Translational Medicine, Department of Public Health and Medical Administration, Faculty of Health Sciences, University of Macau, Macao, ChinaMinistry of Education Frontiers Science Center for Precision Oncology, Cancer Centre and Institute of Translational Medicine, Department of Public Health and Medical Administration, Faculty of Health Sciences, University of Macau, Macao, ChinaMinistry of Education Frontiers Science Center for Precision Oncology, Cancer Centre and Institute of Translational Medicine, Department of Public Health and Medical Administration, Faculty of Health Sciences, University of Macau, Macao, ChinaMinistry of Education Frontiers Science Center for Precision Oncology, Cancer Centre and Institute of Translational Medicine, Department of Public Health and Medical Administration, Faculty of Health Sciences, University of Macau, Macao, ChinaMinistry of Education Frontiers Science Center for Precision Oncology, Cancer Centre and Institute of Translational Medicine, Department of Public Health and Medical Administration, Faculty of Health Sciences, University of Macau, Macao, ChinaMinistry of Education Frontiers Science Center for Precision Oncology, Cancer Centre and Institute of Translational Medicine, Department of Public Health and Medical Administration, Faculty of Health Sciences, University of Macau, Macao, ChinaMUTYH plays an essential role in preventing oxidation-caused DNA damage. Pathogenic germline variations in <i>MUTYH</i> damage its function, causing intestinal polyposis and colorectal cancer. Determination of the evolutionary origin of the variation is essential to understanding the etiological relationship between <i>MUTYH</i> variation and cancer development. In this study, we analyzed the origins of pathogenic germline variants in human <i>MUTYH</i>. Using a phylogenic approach, we searched <i>MUTYH</i> pathogenic variants in modern humans in the <i>MUTYH</i> of 99 vertebrates across eight clades. We did not find pathogenic variants shared between modern humans and the non-human vertebrates following the evolutionary tree, ruling out the possibility of cross-species conservation as the origin of human pathogenic variants in <i>MUTYH</i>. We then searched the variants in the <i>MUTYH</i> of 5031 ancient humans and extinct Neanderthals and Denisovans. We identified 24 pathogenic variants in 42 ancient humans dated between 30,570 and 480 years before present (BP), and three pathogenic variants in Neanderthals dated between 65,000 and 38,310 years BP. Data from our study revealed that human <i>MUTYH</i> pathogenic variants mostly arose in recent human history and partially originated from Neanderthals.https://www.mdpi.com/2218-273X/13/3/429<i>MUTYH</i>pathogenic variantevolutionary originphylogenicarchaeologicalancient humans |
| spellingShingle | Fengxia Xiao Jiaheng Li Philip Naderev Panuringan Lagniton Si Hoi Kou Huijun Lei Benjamin Tam San Ming Wang Evolutionary Origin of <i>MUTYH</i> Germline Pathogenic Variations in Modern Humans Biomolecules <i>MUTYH</i> pathogenic variant evolutionary origin phylogenic archaeological ancient humans |
| title | Evolutionary Origin of <i>MUTYH</i> Germline Pathogenic Variations in Modern Humans |
| title_full | Evolutionary Origin of <i>MUTYH</i> Germline Pathogenic Variations in Modern Humans |
| title_fullStr | Evolutionary Origin of <i>MUTYH</i> Germline Pathogenic Variations in Modern Humans |
| title_full_unstemmed | Evolutionary Origin of <i>MUTYH</i> Germline Pathogenic Variations in Modern Humans |
| title_short | Evolutionary Origin of <i>MUTYH</i> Germline Pathogenic Variations in Modern Humans |
| title_sort | evolutionary origin of i mutyh i germline pathogenic variations in modern humans |
| topic | <i>MUTYH</i> pathogenic variant evolutionary origin phylogenic archaeological ancient humans |
| url | https://www.mdpi.com/2218-273X/13/3/429 |
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