Both noncoding and protein-coding RNAs contribute to gene expression evolution in the primate brain.

Area of Science:

• Genomics
• Evolutionary Biology
• Neuroscience

Background:

• Human-primate cognitive and behavioral differences are striking, yet protein-coding gene regions show little evidence of adaptive change.
• Gene expression alterations are hypothesized to be a primary driver of these cognitive and behavioral distinctions.
• Previous studies using microarrays may have missed a significant portion of differentially expressed transcripts.

Purpose of the Study:

• To assess global transcript abundance changes in the frontal cortex of humans, chimpanzees, and rhesus macaques using digital gene expression: tag profiling (Tag-Seq).
• To identify differentially expressed transcripts, including noncoding regions, and investigate their functional roles and evolutionary significance.
• To explore the overlap between differential gene expression and positive selection in promoter regions as indicators of human evolution.

Main Methods:

• Employed Tag-Seq (digital gene expression: tag profiling) to analyze transcript abundance in the frontal cortex of three individuals from each species: human, chimpanzee, and rhesus macaque.
• Utilized strand-specific information from Tag-Seq to assay expression in both coding and noncoding intragenic regions (sense and antisense transcripts).
• Examined differential gene expression alongside signatures of positive selection in putative promoter regions.

Main Results:

• A substantial fraction of differentially transcribed transcripts identified by Tag-Seq were not detected in previous microarray-based studies.
• Differentially expressed coding region transcripts are enriched in functions related to synaptic transmission, transport, oxidative phosphorylation, and lipid metabolism.
• Many noncoding transcripts exhibit conserved location and expression levels across species, suggesting functional importance. Differential expression in coding regions overlaps with positive selection in promoter regions.

Conclusions:

• Changes in gene expression, particularly involving noncoding transcripts and regulatory elements, are crucial for understanding human-primate cognitive and behavioral evolution.
• Tag-Seq technology reveals novel differentially expressed transcripts and noncoding elements previously unassessed.
• Comparative genomic approaches highlight candidate genes for cognitive functions and neurological disorders.