Alu exaptation enriches the human transcriptome by introducing new gene ends

Area of Science:

• Genomics
• Molecular Biology
• Evolutionary Biology

Background:

• Transposable elements (TEs) are DNA sequences that can change their position within a genome.
• In mammals, TEs are generally silenced but can be co-opted for functional roles.
• Alu elements are a major family of short interspersed nuclear elements (SINEs) in primates.

Purpose of the Study:

• To investigate the functional role of Alu elements in generating transcriptome diversity.
• To identify and characterize new cleavage and polyadenylation sites formed by Alu insertions.
• To explore the evolutionary mechanisms behind the formation of these novel gene ends.

Main Methods:

• Mapping of new gene ends in human genomes to Alu sequences.
• Identification of hotspots for cleavage and polyadenylation site formation.
• Analysis of evolutionary processes, including mutation and Alu insertion, shaping these hotspots.

Main Results:

• Alu elements inserted in sense orientation near genes form new cleavage and polyadenylation sites.
• Three hotspots for new gene end formation were identified, with Alu sequences lacking canonical polyadenylation signals.
• Two hotspots arose from mutations creating polyadenylation signals, while one is linked to Alu insertion.
• Alu elements contribute to 302 new gene end variants affecting 243 genes, leading to gene elongation, truncated proteins, or alternative 3'UTRs.

Conclusions:

• Alu elements are a significant source of transcriptome diversity in humans.
• Evolutionary processes have adapted Alu sequences to generate functional gene variants.
• Alu insertions can lead to alternative splicing and altered protein products, impacting gene regulation and function.