Exon creation and establishment in human genes.

Area of Science:

• Genomics
• Molecular Biology
• Evolutionary Biology

Background:

• Alternative splicing generates numerous species-specific exons.
• Alu elements are key in primate exon creation, but other mechanisms also contribute.
• Splicing requirements for de novo exonization and its regulation over time remain unclear.

Purpose of the Study:

• To investigate the splicing regulatory requirements for de novo exonization.
• To understand how splicing regulation changes during an exon's evolutionary lifespan.
• To develop a model for exon creation and establishment based on regulatory motif abundance.

Main Methods:

• Comparative genomics to define exon sets by evolutionary age.
• Analysis of splice-site strength and regulatory motif abundance.
• Development of a novel measure based on local regulatory density for exon classification.

Main Results:

• Younger exons exhibit weaker splice sites and less consolidated splicing regulation.
• Relative abundance of splicing regulators increases with exon age, enhancing exon inclusion.
• A novel measure of local regulatory density effectively distinguishes true exons from pseudo-exons.

Conclusions:

• Specific sequence environments are essential for exonization and evolve over time.
• A model based on the relative local abundance of regulatory motifs explains exon creation and establishment.
• Alu elements are frequently exonized due to a lack of exonic splicing silencers, supporting their role in primate evolution.