Purifying Selection on Exonic Splice Enhancers in Intronless Genes

Area of Science:

• Molecular Biology
• Genomics
• Evolutionary Biology

Background:

• Exonic splice enhancers (ESEs) are crucial for accurate splicing by promoting splice site recognition.
• Intronless genes lack introns, raising questions about selection pressures on ESEs to avoid spurious splicing.
• Aberrant splicing can lead to non-functional or harmful transcripts.

Purpose of the Study:

• To investigate whether intronless genes are under selection to avoid ESEs.
• To determine the evolutionary fate and functional significance of ESEs in intronless genes.
• To explore the implications for transgene design and synonymous site evolution.

Main Methods:

• Comparative analysis of ESE density and evolutionary rates in intronless versus intron-containing genes.
• Control for base composition biases (GC richness) in sequence analysis.
• Nucleotide-controlled analysis of synonymous site evolutionary rates within ESEs in human and mouse.

Main Results:

• Recent retrocopies show higher ESE density and faster evolution, suggesting ESE loss.
• Intronless genes exhibit lower ESE density than intron-containing genes, partly due to base composition.
• After controlling for biases, ESEs are enriched in both gene types, and ESEs in intronless genes are under purifying selection.

Conclusions:

• Intron loss can lead to the loss of some ESE motifs.
• Remaining ESEs in intronless genes may have functions beyond splice promotion.
• Understanding ESE selection is important for designing intronless transgenes and studying synonymous site evolution.