Table 1.

Hypotheses Suggested for the Evolution of A-to-I RNA Editing Target Sites

	Hypotheses
	H1: Transcriptome Diversity Is Beneficial	H2: G Is Slightly Deleterious	H3: Compensatory Hypothesis	H4: Adaptive Hypothesis (Current Study)
Features
Ancestral state	A	A	G	A
Adaptive value of editing	Editing is adaptive because provides diversity to transcript population.	Editing is very deleterious and currently detected edited sites are generally slightly deleterious.	Editing is adaptive as it reverses the harmful effect of G-to-A mutations.	Editing is adaptive because A-to-I replacements are beneficial at these nucleotide sites.
Relative fitness (s) of the derived allele	s A > sG ≥ sC,T	s A ≥ sG ≥ sC, T	s G ≥ sA > sC,T	s G > sA ≫ sC,T
Population genetics predictions compared with unedited sites
Overall polymorphic rate	Polymorphism at edited sites should be reduced as A-to-G, A-to-C, and A-to-T mutations are slightly deleterious.	Polymorphism at edited sites should be slightly increased as A-to-G mutations are slightly more tolerated than at unedited sites.	Polymorphism at edited sites should be similar or slightly increased as editing somehow reduces the deleterious effect of G-to-A mutations.	Polymorphism at edited sites should be increased as A-to-G mutations are largely adaptive.
Polymorphism type	A, G should be slightly more frequent than A, C and A, T polymorphisms at edited sites.	A, G should be slightly more frequent than A, C and A, T polymorphisms at edited sites.	A, G should be slightly more frequent than A, C and A, T polymorphisms at edited sites.	A, C and A, T polymorphism should be rarely found.
Polymorphic rate at coding regions	Similar or reduced at both edited and unedited sites due to potential deleterious effects at nonsynonymous sites.	Similar or reduced at both edited and unedited sites due to potential deleterious effects at nonsynonymous sites.	Similar or reduced at both edited and unedited sites due to potential deleterious effects at nonsynonymous sites.	Increased at edited sites as the G allele mimics the protein variant obtained through editing.
Synonymous polymorphic rate	Similar at both edited and unedited sites.	Similar at both edited and unedited sites.	Similar at both edited and unedited sites.	Increased at edited sites.
Frequency spectrum of the derived allele	Derived G allele should segregate at similar or lower frequency (i.e., purifying selection or neutral at most).	Derived G allele should segregate at similar frequency (i.e., neutral or nearly neutral).	Derived G allele should segregate at similar frequency (i.e., neutral or nearly neutral).	Derived G allele should segregate at higher frequency.
Nucleotide diversity around edited sites	Similar	Similar	Similar	Reduced