Wenxiang Cai, Weichen Song, Shunying Yu, Min Zhao, Guan Ning Lin
{"title":"人类血统突变调控涉及人类进化的保守基因 NTRK2 和 ITPR1 的 RNA 蛋白结合","authors":"Wenxiang Cai, Weichen Song, Shunying Yu, Min Zhao, Guan Ning Lin","doi":"10.1136/gpsych-2023-101425","DOIUrl":null,"url":null,"abstract":"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. Data are available in a public, open access repository.","PeriodicalId":12549,"journal":{"name":"General Psychiatry","volume":"26 1","pages":""},"PeriodicalIF":5.3000,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Human lineage mutations regulate RNA-protein binding of conserved genes NTRK2 and ITPR1 involved in human evolution\",\"authors\":\"Wenxiang Cai, Weichen Song, Shunying Yu, Min Zhao, Guan Ning Lin\",\"doi\":\"10.1136/gpsych-2023-101425\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"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. Data are available in a public, open access repository.\",\"PeriodicalId\":12549,\"journal\":{\"name\":\"General Psychiatry\",\"volume\":\"26 1\",\"pages\":\"\"},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2024-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"General Psychiatry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1136/gpsych-2023-101425\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PSYCHIATRY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"General Psychiatry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/gpsych-2023-101425","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}
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 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. Data are available in a public, open access repository.
期刊介绍:
General Psychiatry (GPSYCH), an open-access journal established in 1959, has been a pioneer in disseminating leading psychiatry research. Addressing a global audience of psychiatrists and mental health professionals, the journal covers diverse topics and publishes original research, systematic reviews, meta-analyses, forums on topical issues, case reports, research methods in psychiatry, and a distinctive section on 'Biostatistics in Psychiatry'. The scope includes original articles on basic research, clinical research, community-based studies, and ecological studies, encompassing a broad spectrum of psychiatric interests.