Human lineage mutations regulate RNA-protein binding of conserved genes NTRK2 and ITPR1 involved in human evolution

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.