摘要
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.
基金
supported by grants from the 2030 Science and Technology Innovation Key Program of Ministry of Science and Technology of China(No.2022ZD020910001)
the Natural Science Foundation of Shanghai(No.21ZR1428600)
the Medical-Engineering Cross Foundation of Shanghai Jiao Tong University(No.YG2022ZD026,21Z510902252,23X010302269).
作者简介
Correspondenceto:Guan Ning Lin,Dr,nickgnlin@sjitu.edu.cn;first authors:Wenxiang Cai is a PhD student in Shanghai Jiao Tong University School of Biomedical Engineering in China.His main research interest include the basic research of psychiatry diseases,such as schizophrenia ar autism spectrum disorder.ORCID iD:http://orcid.org/0009-0009-0781-4668,contributed equally;first authors:Weichen Song obtained a PhD from Shanghai Jiao Tong University School of Medicine,China in 2023.He is currently a postdoc in Shanghai Jiao Tong University Bio-X Institutes in China.His main research interest include bioinformatics in mental illness and evolutionary biology.contributed equally.
