compensatory evolution

Meer MV, Kondrashov AS, Artzy-Randrup Y & Kondrashov FA 2010 Compensatory evolution in mitochondrial tRNAs navigates valleys of low fitness. Nature 464:279-282.

• fitness landscapes traversed by switches between different AU and GC Watson–Crick nucleotide pairs at complementary sites of mitochondrial transfer RNA stem regions in 83 mammalian species
• such Watson–Crick switches occur 30–40 times more slowly than pairs of neutral substitutions
• alleles corresponding to GU and AC non-Watson–Crick intermediate states segregate within human populations at low frequencies, similar to those of non-synonymous alleles
• a typical Watson–Crick switch involves crossing a fitness valley of a depth of about 10⁻³ or even about 10⁻²
• with AC intermediates being slightly more deleterious than GU intermediates
• this compensatory evolution must proceed through rare intermediate variants that never reach fixation
• simultaneous fixation of two alleles that are individually deleterious may be a common phenomenon at the molecular level