compensatory evolution
Lunzer M, Golding GB & Dean AM 2011 Pervasive cryptic epistasis in molecular evolution. PLoS Genet 6:e1001162.
- Zuckerkandl [15] first proposed that amino acid replacements at one site in a protein might influence the acceptability of amino acid replacements at other sites
- Fitch and Markowitz [16] suggested that as species diverge from a common ancestor their sets of variable sites also diverge to explore different regions of sequence space
- the cryptic epistasis we revealed is consistent with two modes of neutral evolution
- the covarion process
- the nearly neutral process
- in the covarion process, neutral and/or beneficial mutations are fixed in different lineages that, when brought together in the same protein, are deleterious
- in the nearly neutral process successive slightly deleterious alleles are fixed by random genetic drift (particularly during population bottlenecks) until a compensatory mutation arises that, on restoring full activity, is fixed by positive selection (particularly after a population expands)
- our demonstration of rampant cryptic epistasis in IMDH is entirely in accord with a recent insightful analysis of protein evolution that invoked extensive epistasis to account for the retarded divergence seen in ancient proteins
- there the case was made for a rugged fitness landscape characterized by multidimensional sign epistasis that forces sites to be conserved for billions of years until the right combination of amino acids at other sites to allows them to evolve
- our failure to identify compensatory mutations for A94D and A284C is indicative of multidimensional sign epistasis
- that a single replacement is sufficient to compensate the F73L mutation demonstrates that epistasis need not always be multidimensional, however
