Functional persistence of exonized mammalian-wide interspersed repeat elements (MIRs)

Area of Science:

• Genomics
• Molecular Evolution
• Bioinformatics

Background:

• Exonization of mobile elements can generate novel protein domains.
• Previous studies on primate-specific Alu-SINEs showed dynamic gain and loss of exonizations, hindering assessment of their contribution to genomic novelty.
• Alu-SINEs were speculated to be too young for persistent protein exaptation.

Purpose of the Study:

• To investigate the contribution of older mobile elements, mammalian-wide interspersed repeats (MIRs), to protein-coding sequences.
• To determine if MIR exonizations exhibit greater evolutionary persistence compared to Alu-SINEs.

Main Methods:

• Analysis of 107 potential MIR exonizations in humans, focusing on splice site mechanisms.
• Detailed evolutionary retracing of five MIR elements that underwent exonization at different mammalian evolutionary stages.
• Experimental verification of retroposed SINE element expression.

Main Results:

• A mechanism benefiting from 3' splice site selection was substantiated for MIR exonizations.
• Four of five studied MIR elements are expressed as alternatively spliced transcripts, with three conserved across the mammalian phylogenetic tree.
• The fifth MIR element is the first experimentally verified, constitutively expressed retroposed SINE in mammals.

Conclusions:

• Exonized MIR sequences show a pattern of highly conserved alternative and constitutive splicing.
• These findings suggest that exonized transposed elements, particularly older MIRs, can evolve beyond transient states.
• MIR exonizations demonstrate the potential to persist as integral parts of functional proteins, contributing significantly to genomic novelty.