Correlated mutations: a hallmark of phenotypic amino acid substitutions.

ABSTRACT: Point mutations resulting in the substitution of a single amino acid can cause severe functional consequences, but can also be completely harmless. Understanding what determines the phenotypical impact is important both for planning targeted mutation experiments in the laboratory and for analyzing naturally occurring mutations found in patients. Common wisdom suggests using the extent of evolutionary conservation of a residue or a sequence motif as an indicator of its functional importance and thus vulnerability in case of mutation. In this work, we put forward the hypothesis that in addition to conservation, co-evolution of residues in a protein influences the likelihood of a residue to be functionally important and thus associated with disease. While the basic idea of a relation between

SUBMITTER: Kowarsch A 

PROVIDER: S-EPMC2940720 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature