compensatory evolution
Callahan B, Neher RA, Bachtrog D, Andolfatto P & Shraiman BI 2011 Correlated evolution of nearby residues in Drosophilid proteins. PLoS Genet 7:e1001315.
- amino acid substitutions are "clustered" along the protein sequence
- the frequency of additional substitutions is strongly enhanced within ≈10 residues of a first such substitution
- no such clustering is observed for synonymous substitutions
- supporting a "correlation length" associated with selection on proteins as the causative mechanism
- clustering is stronger between substitutions that arose in the same lineage than it is between substitutions that arose in different lineages
- the role of epistasis is directly supported by the tendency of nearby substitutions that arose on the same lineage to preserve the total charge of the residues within the correlation length and by the preferential cosegregation of neighboring derived alleles in our population sample
- we interpret the observed length scale of clustering as a statistical reflection of the functional locality (or modularity) of proteins
- clustering is stronger between substitutions that arose along the same branch of the evolutionary tree than between substitutions that arose in different branches
- pairs of substitutions within codons of each other that arose in the same lineage have a significant tendency to cause compensatory changes to the total charge of the protein
- epistasis between amino acid substitutions contributes significantly to clustering, and the substitution process as a whole
- if epistatic selection is driving the observed clustering we expect that a compensatory mutation will only be found on a chromosome that already carries the first mutation
- we expect the derived states of nearby polymorphic sites to cosegregate
- we can quantify this expectation by estimating the average polarized linkage disequilibrium
