Human coding RNA editing is generally nonadaptive.

Area of Science:

• Molecular Biology
• Genomics
• Evolutionary Biology

Background:

• RNA editing, particularly A-to-G conversions, is known to cause severe disorders when impaired at specific coding sites.
• Recent genomic studies have significantly increased the number of identified human coding RNA editing sites, necessitating a re-evaluation of their functional significance.

Purpose of the Study:

• To investigate the prevalence and adaptive nature of coding RNA editing in humans.
• To determine if observed RNA editing events are generally beneficial or a consequence of enzyme targeting.

Main Methods:

• Analysis of 1,783 human coding A-to-G RNA editing sites.
• Examination of the relationship between editing frequency/level and site/gene importance.
• Evolutionary analysis of edited vs. unedited sites and conservation patterns.

Main Results:

• RNA editing frequency and level decrease as the importance of the site or gene increases.
• Evolutionarily, edited A's are more likely to be replaced by G's than by other bases.
• Nonsynonymously edited A's that are least evolutionarily conserved show the highest editing levels.

Conclusions:

• The overall nature of coding RNA editing appears to be nonadaptive, despite a few beneficial sites.
• Most observed coding RNA editing likely results from "tolerable promiscuous targeting" by RNA editing enzymes.
• The original physiological functions of these RNA editing enzymes remain largely unknown.