A single mutation in the ACTR8 gene associated with lineage-specific expression in primates

Area of Science:

• Genomics
• Evolutionary Biology
• Molecular Biology

Background:

• Alternative splicing (AS) significantly increases transcriptomic diversity and proteomic complexity.
• Alu elements, primate-specific transposable elements (TEs), can act as regulatory sites for AS.
• A novel AluSz6-exonized ACTR8 transcript was previously identified in the crab-eating monkey.

Purpose of the Study:

• To elucidate the molecular mechanism behind AluSz6 exonization in the ACTR8 gene.
• To investigate the evolutionary and functional impacts of this exonization event in primates.

Main Methods:

• RT-PCR and genomic PCR were employed to analyze AluSz6 exonization in the ACTR8 gene.
• Expression analysis of the AluSz6-exonized transcript was conducted across nine primate species.
• In silico analysis was used to assess the functional impact of resulting protein isoforms.

Main Results:

• AluSz6 integration predates the divergence of simians and prosimians.
• The Alu-exonized ACTR8 transcript exhibits lineage-specific expression in Old World monkeys, apes, and humans, driven by a single G duplication creating a novel 5' splice site.
• Resulting C-terminus deleted isoforms were found to be non-disruptive.

Conclusions:

• A single G duplication within the AluSz6 TE sequence is identified as the source of exonization and AS.
• This mutation influences the evolutionary trajectory of ACTR8 gene expression during primate diversification.