Human lineage mutations regulate RNA-protein binding of conserved genes NTRK2 and ITPR1 involved in human evolution
Background The role of human lineage mutations (HLMs) in human evolution through post-transcriptional modification is unclear.Aims To investigate the contribution of HLMs to human evolution through post-transcriptional modification.Methods We applied a deep learning model Seqweaver to predict how HL...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2024-06-01
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| Series: | General Psychiatry |
| Online Access: | https://gpsych.bmj.com/content/37/3/e101425.full |
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| author | Min Zhao Weichen Song Shunying Yu Wenxiang Cai Guan Ning Lin |
| author_facet | Min Zhao Weichen Song Shunying Yu Wenxiang Cai Guan Ning Lin |
| author_sort | Min Zhao |
| collection | DOAJ |
| description | Background The role of human lineage mutations (HLMs) in human evolution through post-transcriptional modification is unclear.Aims To investigate the contribution of HLMs to human evolution through post-transcriptional modification.Methods We applied a deep learning model Seqweaver to predict how HLMs impact RNA-binding protein affinity.Results We found that only 0.27% of HLMs had significant impacts on RNA-binding proteins at the threshold of the top 1% of human common variations. These HLMs enriched in a set of conserved genes highly expressed in adult excitatory neurons and prenatal Purkinje neurons, and were involved in synapse organisation and the GTPase pathway. These genes also carried excess damaging coding mutations that caused neurodevelopmental disorders, ataxia and schizophrenia. Among these genes, NTRK2 and ITPR1 had the most aggregated evidence of functional importance, suggesting their essential roles in cognition and bipedalism.Conclusions Our findings suggest that a small subset of human-specific mutations have contributed to human speciation through impacts on post-transcriptional modification of critical brain-related genes. |
| format | Article |
| id | doaj-art-e2339913799b4d8bb89b5f52999d8cda |
| institution | Kabale University |
| issn | 2517-729X |
| language | English |
| publishDate | 2024-06-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | General Psychiatry |
| spelling | doaj-art-e2339913799b4d8bb89b5f52999d8cda2025-01-29T15:35:11ZengBMJ Publishing GroupGeneral Psychiatry2517-729X2024-06-0137310.1136/gpsych-2023-101425Human lineage mutations regulate RNA-protein binding of conserved genes NTRK2 and ITPR1 involved in human evolutionMin Zhao0Weichen Song1Shunying Yu2Wenxiang Cai3Guan Ning Lin41 Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China1 Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China1 Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China1 Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China1 Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, ChinaBackground The role of human lineage mutations (HLMs) in human evolution through post-transcriptional modification is unclear.Aims To investigate the contribution of HLMs to human evolution through post-transcriptional modification.Methods We applied a deep learning model Seqweaver to predict how HLMs impact RNA-binding protein affinity.Results We found that only 0.27% of HLMs had significant impacts on RNA-binding proteins at the threshold of the top 1% of human common variations. These HLMs enriched in a set of conserved genes highly expressed in adult excitatory neurons and prenatal Purkinje neurons, and were involved in synapse organisation and the GTPase pathway. These genes also carried excess damaging coding mutations that caused neurodevelopmental disorders, ataxia and schizophrenia. Among these genes, NTRK2 and ITPR1 had the most aggregated evidence of functional importance, suggesting their essential roles in cognition and bipedalism.Conclusions Our findings suggest that a small subset of human-specific mutations have contributed to human speciation through impacts on post-transcriptional modification of critical brain-related genes.https://gpsych.bmj.com/content/37/3/e101425.full |
| spellingShingle | Min Zhao Weichen Song Shunying Yu Wenxiang Cai Guan Ning Lin Human lineage mutations regulate RNA-protein binding of conserved genes NTRK2 and ITPR1 involved in human evolution General Psychiatry |
| title | Human lineage mutations regulate RNA-protein binding of conserved genes NTRK2 and ITPR1 involved in human evolution |
| title_full | Human lineage mutations regulate RNA-protein binding of conserved genes NTRK2 and ITPR1 involved in human evolution |
| title_fullStr | Human lineage mutations regulate RNA-protein binding of conserved genes NTRK2 and ITPR1 involved in human evolution |
| title_full_unstemmed | Human lineage mutations regulate RNA-protein binding of conserved genes NTRK2 and ITPR1 involved in human evolution |
| title_short | Human lineage mutations regulate RNA-protein binding of conserved genes NTRK2 and ITPR1 involved in human evolution |
| title_sort | human lineage mutations regulate rna protein binding of conserved genes ntrk2 and itpr1 involved in human evolution |
| url | https://gpsych.bmj.com/content/37/3/e101425.full |
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