Evolutionary Origin of Human <i>PALB2</i> Germline Pathogenic Variants
<i>PALB2</i> (Partner and localizer of BRCA2) is crucial for repairing DNA double-stranded breaks (DSBs) through homologous recombination (HR). Germline pathogenic variation in <i>PALB2</i> disrupts DNA damage repair and increases the risk of Fanconi Anemia, breast cancer, an...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-07-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/14/11343 |
| _version_ | 1797589012793262080 |
|---|---|
| author | Jia Sheng Chian Jiaheng Li San Ming Wang |
| author_facet | Jia Sheng Chian Jiaheng Li San Ming Wang |
| author_sort | Jia Sheng Chian |
| collection | DOAJ |
| description | <i>PALB2</i> (Partner and localizer of BRCA2) is crucial for repairing DNA double-stranded breaks (DSBs) through homologous recombination (HR). Germline pathogenic variation in <i>PALB2</i> disrupts DNA damage repair and increases the risk of Fanconi Anemia, breast cancer, and ovarian cancer. Determination of the evolutionary origin of human <i>PALB2</i> variants will promote a deeper understanding of the biological basis of <i>PALB2</i> germline variation and its roles in human diseases. We tested the evolution origin for 1444 human <i>PALB2</i> germline variants, including 484 pathogenic and 960 benign variants. We performed a phylogenic analysis by tracing the variants in 100 vertebrates. However, we found no evidence to show that cross-species conservation was the origin of <i>PALB2</i> germline pathogenic variants, but it is indeed a rich source for <i>PALB2</i> germline benign variants. We performed a paleoanthropological analysis by tracing the variants in over 5000 ancient humans. We identified 50 pathogenic in 71 ancient humans dated from 32,895 to 689 before the present, of which 90.1% were dated within the recent 10,000 years. <i>PALB2</i> benign variants were also highly shared with ancient humans. Data from our study reveal that human <i>PALB2</i> pathogenic variants mostly arose in recent human history. |
| first_indexed | 2024-03-11T01:00:15Z |
| format | Article |
| id | doaj.art-0216d40ce31641d4943e872ffb1b5a73 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T01:00:15Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0216d40ce31641d4943e872ffb1b5a732023-11-18T19:37:53ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-07-0124141134310.3390/ijms241411343Evolutionary Origin of Human <i>PALB2</i> Germline Pathogenic VariantsJia Sheng Chian0Jiaheng Li1San Ming Wang2MoE Frontiers Science Center for Precision Oncology, Cancer Center and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, MacaoMoE Frontiers Science Center for Precision Oncology, Cancer Center and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, MacaoMoE Frontiers Science Center for Precision Oncology, Cancer Center and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macao<i>PALB2</i> (Partner and localizer of BRCA2) is crucial for repairing DNA double-stranded breaks (DSBs) through homologous recombination (HR). Germline pathogenic variation in <i>PALB2</i> disrupts DNA damage repair and increases the risk of Fanconi Anemia, breast cancer, and ovarian cancer. Determination of the evolutionary origin of human <i>PALB2</i> variants will promote a deeper understanding of the biological basis of <i>PALB2</i> germline variation and its roles in human diseases. We tested the evolution origin for 1444 human <i>PALB2</i> germline variants, including 484 pathogenic and 960 benign variants. We performed a phylogenic analysis by tracing the variants in 100 vertebrates. However, we found no evidence to show that cross-species conservation was the origin of <i>PALB2</i> germline pathogenic variants, but it is indeed a rich source for <i>PALB2</i> germline benign variants. We performed a paleoanthropological analysis by tracing the variants in over 5000 ancient humans. We identified 50 pathogenic in 71 ancient humans dated from 32,895 to 689 before the present, of which 90.1% were dated within the recent 10,000 years. <i>PALB2</i> benign variants were also highly shared with ancient humans. Data from our study reveal that human <i>PALB2</i> pathogenic variants mostly arose in recent human history.https://www.mdpi.com/1422-0067/24/14/11343<i>PALB2</i>evolutionary originphylogeneticpaleoanthropology |
| spellingShingle | Jia Sheng Chian Jiaheng Li San Ming Wang Evolutionary Origin of Human <i>PALB2</i> Germline Pathogenic Variants International Journal of Molecular Sciences <i>PALB2</i> evolutionary origin phylogenetic paleoanthropology |
| title | Evolutionary Origin of Human <i>PALB2</i> Germline Pathogenic Variants |
| title_full | Evolutionary Origin of Human <i>PALB2</i> Germline Pathogenic Variants |
| title_fullStr | Evolutionary Origin of Human <i>PALB2</i> Germline Pathogenic Variants |
| title_full_unstemmed | Evolutionary Origin of Human <i>PALB2</i> Germline Pathogenic Variants |
| title_short | Evolutionary Origin of Human <i>PALB2</i> Germline Pathogenic Variants |
| title_sort | evolutionary origin of human i palb2 i germline pathogenic variants |
| topic | <i>PALB2</i> evolutionary origin phylogenetic paleoanthropology |
| url | https://www.mdpi.com/1422-0067/24/14/11343 |
| work_keys_str_mv | AT jiashengchian evolutionaryoriginofhumanipalb2igermlinepathogenicvariants AT jiahengli evolutionaryoriginofhumanipalb2igermlinepathogenicvariants AT sanmingwang evolutionaryoriginofhumanipalb2igermlinepathogenicvariants |