Distinguishing functional amino acid covariation from background linkage disequilibrium in HIV protease and reverse transcriptase.

ABSTRACT: Correlated amino acid mutation analysis has been widely used to infer functional interactions between different sites in a protein. However, this analysis can be confounded by important phylogenetic effects broadly classifiable as background linkage disequilibrium (BLD). We have systematically separated the covariation induced by selective interactions between amino acids from background LD, using synonymous (S) vs. amino acid (A) mutations. Covariation between two amino acid mutations, (A,A), can be affected by selective interactions between amino acids, whereas covariation within (A,S) pairs or (S,S) pairs cannot. Our analysis of the pol gene--including the protease and the reverse transcriptase genes--in HIV reveals that (A,A) covariation levels are enormously higher than for either (A,

SUBMITTER: Wang Q 

PROVIDER: S-EPMC1950573 | biostudies-literature | 2007 Aug

REPOSITORIES: biostudies-literature