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Updated: Jun 25, 2025

Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins
Published on: August 9, 2019
Human lineage mutations regulate RNA-protein binding of conserved genes NTRK2 and ITPR1 involved in human evolution
Wenxiang Cai1,2, Weichen Song1,2, Shunying Yu1,2
1Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
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.
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